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Board Studying > CU Biochem Course and NAMA > Flashcards

CU Biochem Course and NAMA Flashcards

1
Q

What is the difference between classic PKU, mild PKU< and hyperpheylalaninemia?

A

Untreated Phe levels:

>1200umol/L - classic PKU

600-1200umol/L - mild PKU

<600umol/L - hyperphe

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2
Q

Mousy odored urine, light hair, eczema, developmental delay, white matter hyperintensities

A

Untreated PKU

  • treatment needs to start within 1 month of life
  • “pseudoleukodystrophy”
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3
Q

What is pegvaliase

A

Enzyme substitution for PAH deficiency (PKU)

  • plant enzyme (phe ammonia lyase)
  • Goal to enhance Phe tolerance and normalize diet
  • still need tyrosine

- Approved for 16+

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4
Q

Elements of PKU diet

A

Low Phe

Supplement tyrosine and tryptophan (share same large neural AA transporter as Phe)

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5
Q

What is a goal of sapropterin trial in PKU?

A

20mg/kg/day

Infant: 24 hour trial -> >30% reduction in Phe = positive (no dietary changes)

Adult: 48hr to 30 day trial

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6
Q

Mutatons in which subunit of BCKDH can be thiamine (B1) responsive?

A

E2 subunit

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7
Q

What is the role of IV destroxe (glucose) in metabolic decompensation?

A
  • Prevent gluconeogenesis that drives protein breakdown
  • Provide calories
  • Drives insulin production (anabolic)
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8
Q

Tyrosine aminotransferase deficiency

A

Tyrosinemia type 2

PAA: high Tyr, Phe

UOA: 4-OH phenylpyruvate/lactate/acetate

  • corneal lesions, hyperkeratosis
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9
Q

UOA: 4-OH phenylpyruvate, 4OH phentyllactate, 4OHphentylacetate

A

Tyrosinemia type II

Tyrosine aminotransfearse deficiency

TAT gene

PAA: high Tyr, Phe

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10
Q

4-hydroxyphentylpyruvic dioxygenase deficiency

A

Tyrosinemia type III

HPD gene

  • PAA: high Tyr, Phe
  • Uncertain clinical significance, may have keratitis
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11
Q

Renal fanconi, liver/renal disease, porphyric crisis, hepatocellular carcinoma

A

Tyrosinemia type I

Fumarylacetoacetate hydrolase deficiency

FAH

  • High AFP, SUAC, Met (liver disease)
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12
Q

high AFP, methionine, aaminolaevulinic acid (ALA)

A

Tyrosinemia type I

FAH

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13
Q

What are the 3 presentations for tyrosinemia type I?

A
  • Hepato: early severe liver disease
  • Renal: rickets (renal fanconi)
  • Acute intermittent: porphyria like attacks
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14
Q

What are the toxic compounds in tyrosinemia type I?

A

FAH deficiency

  • Fumarylacetoacetate, Maleylacetoacetate, Succinylacetone
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15
Q

Which steps in porphyrin synthesis does SUAC inhibit?

A

ALAD and HMBS

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16
Q

What is 2-nitro-4-trifluoromethylbenzoyl - 1,3- cyclohexane-dione used to treat?

A

Tyrosinemia type I

2-nitro-4-trifluoromethylbenzoyl - 1,3- cyclohexane-dione

NTBC = nitsinone

  • inhibits 4-OHphentylpyrvic acid dioxygenase
  • Goal: blood level >40 (enzyme inhibition 99%); SUAC suppression
  • restrict Phe/Tyr to goal <600 umol/L in blood
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17
Q

corneal crystals, plantarpalmar hyperkeratosis with pits

A

Type II or III tyrosinemia

TAT (tyrosine aminotransferase), HPD (hydroxyphenylpyruvate dioxygenase)

  • May also have ID/seizures if untreated
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18
Q

If NBS shows high Tyr and normal SUAC, what should you do next?

A

Repeat at 6 weeks -> if normal this is transient tyrosinemia of newborn

-> if abnormal work up tyrosinemia type II and III

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19
Q

What vitamin will 50% of Cystathione beta syntase deficiency respond to?

A

B6 - pyridoxine

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20
Q

What is treatment of homocystinuria is B6 unreponsive?

A

Folate (B9)

B12 if deficient

Low protein (met)

Betaine (alternate remethylation pathway)

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21
Q

Which UCD has fair fragility (Trichorrhexis nodosa) + rash?

A

ASL deficiency

  • also increased liver disease
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22
Q

Which UCD enzymes are in the mitochondria?

A

N-acetylglutamate synthetase

Carbamoyl phsophate synthetase

Carbonic anhydrase 5A (CAVA) - Makes bicarb necessary for carboxylases (including CPS)

Ornithine transcarbamylase

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23
Q

Why does citrulline bruild up in citrin deficiency?

A

Aspartate is stuck and mitochondria and unable to conjugate with citrulline in cytoplasm (ASS) to form arginosuccinate.

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24
Q

Why is Lys high in OTC deficiency?

A

Shortage of 2-oxoglutarate

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25
Q

Gold standard testing for OTC in females

A

Liver enzyme funciton testing

  • Molecular testing cannot find mutation in 10%
  • Orotic acid/glutamine may be normal
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26
Q

Why does Carbonic anhydrase 5-A deficiency cause hyperammonemia?

A

CAVA synthesizes bicarb in mitochondria used by CPSI -> Proximal UCD

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27
Q

What is phenylbutyrate?

A

Prodrug to phentylacetate -> conjugates to glutamine

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28
Q

Which UCD presents with spastic diplegia and intellectual disability?

A

Arginase deficiency

+ growth arrest

  • check PAA when working up DD!
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29
Q

What are the cofactors for glycine cleavage system?

A

Lipoate and pyridoxal-Phosphate

  • Deficiency can cause variant NKH
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30
Q

high CSF/serum glycine, high homocysteine, high MMA

A

HCFC1 - Cobalamin X

  • XL
  • Transcription factor for glycine cleavage system and Cbl pathway
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31
Q

What drugs should be avoided in NKH?

A

Valproic acid and vigabatrin -> inhibit residual enzyme activity

(both can cause iatrogenic glycine elevation)

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32
Q

98% of NKH are caused by variants in what 2 genes?

A

GLDC and AMT

P and T protein

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33
Q

What is treatment for NKH?

A

Benzoate (conjugates with glycine to form hippurate) -> goal plasma glycine 120-300uM

Glycine restriction

Ketogenic diet (glycine is gluconeogenic substrate)

NMDA blockade: Dextromethorphan, ketamine

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34
Q

What is serine synthesized from?

A

3-phosphoglycerate (glycolysis intermediate)

3PG Dehydrogenase -> Phosphserine aminotransferase -> phosphosering phosphatase

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35
Q

CSF: low glycine, low serine

A

Serine synthesis defect

PGDH, PSAT, PSPH

  • Severe hypomyelination and epilepsy
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36
Q

What is the treatment for neu laxova syndrome?

A

Serine supplementation + glycine supplementation

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37
Q

What is the vulnerable window in GA1

A

3 months - 2 years

  • Up to 6yo can be affected
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38
Q

High Glutaric acid, 3-OH glutaric acid

A

GA1

GCDH deficiency

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39
Q

What is C5DC?

A

Glutaryl carnitine

  • look for GA1
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40
Q

What is treatment for GA1?

A

1) avoid catabolism
2) low lysine/trytophan
3) Carnitine

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41
Q

What does 2-aminoadipic semialdehyde dehydrogenase deficiency cause?

A

Pyridoxine dependent epilepsy

ALD7A1 - antiquitin

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42
Q

High aminoadipid acid semialdehyde, pipecolic acid, 6-oxo-pipecolate

A

pyridoxine dependent epilepsy

ALD7A1

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43
Q

What is the second most common B6 responsive epilepsy? (after ALDH7A1)

A

Pyridoxine 5 phosphate oxidase deficiency

PNPO

  • Converts pyridoxine to active form
  • Normal cognitive development (not true in ALDH7A1)
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44
Q

What is the treatment for alpha-aminoadipic semialdehyde DH deficiency or pyridoxamine-5-phosphate oxidase deficiency?

A

Pyrixodine depedent epilepies (ALDH7A1 and PNPO)

  • Will always respond to pyridoxal phosphate (active form)
  • might repsond to pyridoxine
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45
Q

Which pathways are mostly affected in riboflavin deficiency?

A

ETFDH (GA2)

FAOD

BCAA metabolism

Complex I

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46
Q

Axonal neuropathy, hearing loss, bulbar weakness, myopathy

A

Riboflavin transporter defects

RFVT2 and RFVT3

Brown-Vialetto- Van Laere

  • Tx: Riboflavin
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47
Q

Low 5-methyltetrahydrofolate in CSF

A

Folate transporter deficiency (FOLR1) or Kearns-Sayre

  • Ataxia, epilepsy, demyelination
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48
Q

megaloblastic anemia, diabetes, SNHL in infancy

A

Thiamin-responsive megaloblastic anemia

SLC19A2

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49
Q

3 thiamine reponsive encephalopathies

A

TPK1

SLC19A3

SLC25A19 (also severe congenital microcephaly)

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50
Q

What does G6Pase translocase deficiency cause?

A

GSD1b

  • GSD1 + neurtropenia

GSD1a is caused by G6Pase (most common GSD)

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51
Q

Are glucagon levels low or high in GSD1?

A

Elevated

Glucagon drives gluconeogenesis and glycogenolysis, both are defective in G6Pase deficiency

  • Insulin is low until fed
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52
Q

Doll like face, buttock fat pad accumulation, hepatomegaly, nephromegaly, hypotonia, bleeding tendency

A

GSD1

  • No nephro/hepatomegaly in CDG-PMM2
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53
Q

Compare Von Gierke and Cori disease

A

GSD1 (G6Pase) vs GSD3 (amylo-1,6-glucosidase)

  • GSD3 has milder hypoglycemia (gluconeogenesis intact), but more early liver dysfunction
  • Give high protein diet for GSD3 (glucogeogenesis)
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54
Q

What is the mechanism of injury in Anderson disease?

A

GSD4 - a-1,4-glucan-6-glucosyltransferase deficiency (branching)

  • Unbanched glycogen (polyglucosan) build -> toxic -> hepatosplenomegaly
  • other GSDs have branched glycogen buildly
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55
Q

Liver pathology findings for Andersen’s disease

A

GSD4 - branching enzyme

  • Unbranched glycogen (polyglusocan) accumulation
  • path: PAS stain positive, diastase-resistant with amylopectin-like inclusions
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56
Q

Which GSDs have postprandial hyperglycemia?

A

GSD0 - unable to store BG as glycogen

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57
Q

What can patients with fanconi Bickel syndrome get that GSD1 patients canno?

A

Fructose

  • Fanconi bickel = glucose/galactose transporter defect
  • in GSD1 fructose cannot be used because it is convered into G6P
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58
Q

Treatment for tauri disease?

A

Avoid sugars/glucose - no NOT give D10 when sick

  • Glucose is high but not sensed by mitochondrial/cannot be used for glycolysis.
  • FAO inhibited by high glucose levels
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59
Q

In which GSDs should you avoid giving excess glucose?

A

GSD4 (Andersen) and GSD9 (Tauri)

  • Andersen -> more glucose -> more polyglucosan; give proteins to promote gluconeogensis instead
  • Tauri -> Glycolysis is blocks, reduce glucose to release inhibition on FAO
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60
Q

microcephaly, thin upper lip, long philtrum, wide nasal bridge, DD, leigh syndrome

A

Pyruvate dehydrogenase deficiency

Most common X linked

  • Fetal alcohol syndrome-like face + leigh syndrome
  • high pyruvate -> high lactate + alanine
  • Lacate/pyruvate ratio low
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61
Q

Treatment for PDH deficiency

A

Ketogenic diet, thiamine, carnitine, lipoic acid

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62
Q

Name the 3 glyconeogenic enzymes

A

Pyruvate Carboxylase, Fructose 1,6 bis phosphatase, Glucose-6-phosphatase

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63
Q

Cystic brain lesions, FTT, metabolic acidosis

PAA: High Cit, Ala, Lys, Pro

UOA: 2-oxoglutaric acid (aKG)

High lacate/pyruvate with increased ratio >20

high acetoacetate/betahydroxy-butyrate ratio

High ammonia

A

Pyruvate Carboxylase deficiency

  • Biotin Dependent
  • TCA cycle and gluconeogenesis affected

High lacate -> high ala, proline (proline oxidase suppressed)

Low OAA (precursor) -> low aspartate and glutamate

Low aspartate -> high citrulline and ammonia

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64
Q

Compare F1,6BP deficiency with HFI

A
  • F1,6BP can tolerate more fructose
  • F1,6BP presents more like GSD1 - F1,6BP buildup inhibits G6Pase
  • FBP: Pseudohypertriglyceridemia, high glycerol, glycerol 3 phosphate
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65
Q

What is the pathophys of HFI?

A

Aldolase B deficiency

Toxic accumulation of F1P -> impaired gluconeogensis and glycogenolysis -> lactic acidosis, hypolgycemia, liver failure

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66
Q

Promoter deletion + N314D/Q188R

A

Biochemical (Duarte) Galactosemia

GALT (~25% activity)

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67
Q

UOA: high glycerol-3-phosphate, glycerol

high TG

high alanine, ketones

A

Fructose 1,6 BP

Glycerol-3-phosphate is not seen in glycerolkinase

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68
Q

Contrast HFI and FBPase deficiency

A

HFI: childrne have no cavities (Aversion to sweets), FTT with fructose ingestion, RTA

FBPase: can tolerate fructose, no renal involvement, UOA with glycerol/glycerol-3-phosphate

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69
Q

Q188R

K285N

L195P

A

classic galactosemia

GALT (<1% activity)

  • early e.coli sepsis, FTT, liver disease

+ Premature ovarian insufficiency and DD

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70
Q

S125L

A

Variant galactosemia

GALT (1-10% activity)

Same early presentation (e-coli sepsis, FTT, liver disease etc)

  • Normal development/reproduction
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71
Q

Urine polyol analysis: high ribitol, D-arabitol, erythritol, sedoheptulose

A

Transaldolase

TALDO

Liver, HSM, anemia, thrombocytopenia, congenial anomalies

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72
Q

Urine polyol: high ribitol, D-arabitol

A

Ribose-5-P Isomerase

RPIA

  • Leuckoencephalopathy, ataxia, neuropathy
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73
Q

What are the steps of ß-Oxidation?

A

1) Dehydrogenase (create 2,3 double bond)
2) hydratase (add 3-OH)
3) dehydroganse (create 3 double bonded O)
4) thiolase (remove ketone)

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74
Q

Treatment for FAODs

A
  • low fat diet
  • avoid catabolism
  • triheptanoin (Long chain and above) - can freely diffuse into mitochondrial and bypass carnitine shuttle/long chain breakdown
  • Carnitine (allows urine clearance of FA)
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75
Q

What is OCTN2 deficiency?

A

Primary carnitine deficiency (Carnitine transporter)

(SLC22A5)

  • carnitine cannot be reabsorbed in kidney -> unavailable in liver/muscle/heart
  • Presents with hepatic encephalopathy, cardiac, hypoglycemia, rhabdo
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76
Q

What should be done if a baby is NBS positiove for low carnitine but has normal plasma F/T carnitine testing?

A

Screen for mother with primary carnitine deficiency

  • Carnitine comes from breastmilk for young infants
  • Mothers w/ carnitine deficiency will have NBS positive child and are at risk for sudden death
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77
Q

UOA: Hexanoylglycine

A

MCAD

ACADM

ACP: high C6, C8, C10:1

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78
Q

Why are dicarboxylic acids elevated in urine in FAOD?

A

Long chain FAs build up in cytoplasm go into microsomes -> gets converted into dicarboxylic acids

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79
Q

What is the next step if NBS is positive with elevated C14:1 but plasc ACP is normal?

A

VLCAD gene sequencing (ACP may be normal between episodes)

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80
Q

FAOD + neuropathy, RP, and maternal preeclampia/HELLP/fatty liver

A

LCHAD/TFP

  • hydroxylated FAs can flow into mom and accumulate
  • TFP also modified cardiolipin (may explain extra symptoms)
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81
Q

if NBS is high for C16OH and ACP/UOA are normal, what is the next step?

A

Sequencing for LCHAD/TFP - cannot rule out wth ACP alone

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82
Q

UOA: High ethylmalonic acid, n-butrylglycine, and methylsuccinic acid

A
  • SCAD
  • Isobutyryl glycinuria (+ high isobutyrylgylcine)
  • Ethylmaloni encephalopathy (+ persistent lactic acidosis) - ETHE
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83
Q

What is the final electron acceptor of dehydrogenases?

A

ETFDH

  • Causes GA2 -> mulitiple DH issues -> multiple chain length elevations of ACP
  • Riboflavin is cofactor
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84
Q

What are the main ketogenic AAs?

A

Leucine, isoleucine, lysine

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85
Q

Hypoketotic hypoglycemia, dicarboxylic aciduria, 4-hydroxy-6-methyl-2-pyrone

  • normal ACP
A

3-Hydroxy-3-emethly-glutaryl-CoA synthase deficiency (HMG-coa Synthase)

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86
Q

UOA: 3-hydroxy-3-methylglutaric acid, 3-methylglutaric acid

  • hyperammonia, hypoketotic hypoglycemia
A

2-Hydroxy-3-methlyglutayl-CoA Lyase deficiency (HMG-coa Lyase)

  • high HMG and MG (3-hydroxy-3-methylglutaric acid, 3-methylglutaric acid)
  • C6DC (3 methylglutaryl-carnitine), C5OH (3-OH-isovaleryl carnitine)
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87
Q

high D-3-hyroxybutyrate, tiglylglycine, 2-methyl-3-hydroxybutryrate, 2-methylacetoacetate

A

beta-ketothiolase (T2)

  • ACAT1
  • High ketones during illness + isoleucine intermediates
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88
Q

High ketones with normal dicarboxylic acids

A

Disorders of ketolysis

  • physiological ketosis comes from FAO -> thus dicarboxylic acids (adipid, suberic, and sebacic) also build up
  • HIgh ketones with normal dicarboxylic acids -> usually SCOT deficiency
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89
Q

High ketones during fed and fasting state

A

Succinyl-Coa - oxoacid-Coa transferase (SCOT)

SCOT/OXCT1 gene

  • Do not see elevated dicarboxylic acids (adipic, suberic, sebacic) which are seen in physiological ketosis

DDx: Monocaroboxylic transporter 1 (MCT1) deficinecy -> ketone transporter

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90
Q

What is Monocarboxylic Transporter 1 (MCT1) deficiency?

A

Ketone transporder defect

SLC16A1

  • looks similar to SCOT -> episodic ketoacidosis
  • Increased acetoacetate + 3 OH butyric acid, normal dicarboxylic acids
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91
Q

Renal fanconi, renal failure, cornea crystals, hypothyroidism, hypogonadism, myopathy

A

Cystinosis

Lysosomal Cystine transporter

  • Tx Cysteamine eyedrops + Tablets
  • Cysteine (Cystine + Cysteamine) has own transporter; another cysteine can be added and use Lysine transporder
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92
Q

GLA N215S

A

Cardiac Variant Fabry

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93
Q

GLA A143T

A

VUS Fabry

  • Most common on NBS
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94
Q

Alkylglycerone 3-phosphate acyltransfearse deficiency

A

GNPAT - RCDP

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95
Q

Alkylglycerone 3-phosphate synthase deficiency

A

AGPS

  • RCDP
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96
Q

Most common cause of RCDP

A

PEX7

  • Low plasmalogen, also high phytanic acid
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97
Q

Fatty Alcholol Reductase deficiency

A

RCDP without RCDP

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98
Q

PEX5L deficiency

A

RCDP

  • mutation in specific long isoform of PEX5 - mutations in exon 9
  • Results in abnormal PEX7 activity
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99
Q

Metaphyseal flaring, epiphyseal stippling, coronal vertebral clefts, mineralization of intervertebral disks

A

RCDP

  • ARSE - XL -Male
  • Sterol-8-isomerase - XL - Females (male lethal)
  • Wafarin/VitK, EtOH, Phenytoin
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100
Q

high oxalate, glyoxalate

A

Primary hyperoxaluria type I

AGT

Alanine-glyoxylate aminotransferase - peroxisomal enzymes

  • Renal stones + nephrocalcinosis
  • Tx: Pyrixosone, Hydration, Liver/Kidney transplant
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101
Q

Neuropathy, loss of night vision, deafness, conduction defects, short metacarpals/metatarsals

A

Adult refsum disease

  • Phytanol-CoA hydroxylase deficiency
  • High phytanic (found in animal fats and plants), low pristanic acid
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102
Q

Which amino acides do glycosylation occur on?

A

N-linked - Asparagine

O-linked - Serine or threonine

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103
Q

Which organelles does glycosylation occur in?

A

Early - cytosol and ER (Type I isoelectric focusing pattern)

Late - Golgi (Type II pattern)

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104
Q

What methods to defect CDG is more sensitive and specific than isoelectric focusing?

A

Mass Spec

  • Can see both N and O linked CDGs
  • Can use flow-intection electrospray ionization to digest N-glycan off protein and get more specific results
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105
Q

What does phosphomannomutase do?

A

PMM2 -> converst mannose 6P to mannose 1P

Causes CDG

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106
Q

Which CDG causes protein losing enteropathy and hyperinsulinism with no neurological diasease

A

MPI - CDG1b

  • treat w/ mannose
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107
Q

Which CDG is associated with elevated alk phos?

A

GPI anchor disorders

PIGA, PIGN, PIGO

  • Seizures and DD
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108
Q

m.8993 T>G

A

Leigh syndrome - ATP6

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109
Q

m.3243 A>G

A

MELAS

rRNA leu

  • Diabetes + hearing loss most common
  • Complex I, III, IV deficiency
  • Treat w/ Arg/Cit/Tauring
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110
Q

m.8344A>G

A

MERRF

tRNA Lys

+ lipomas

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111
Q

m.1555G>A

A

Hearing loss when exposed to aminoglycosides

(Mitocondria are derived from bacteria symbiotes!)

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112
Q

Homoplasmic m.11778 G>A (MT-ND4)

A

LHON

  • Males > females
  • incomplete penetrance
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113
Q

names 2 mtDNA deletion syndromes

A

Kearns-Sayre = CPEO + conduction block, RP, diabetes, renal, ID, hearing loss

Pearson Syndrome = KSS + sideroblastic anemia and exocrine pancreas dysfunction

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114
Q

SDH deficiency

A

AD paraganglioma + pheo

AR Leigh syndrome

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115
Q

Leigh syndrome + hypertrichosis/hirsutism

A

SURF1

  • nuclear gene involved in complex IV assembly
  • most common leigh gene
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116
Q

X-linked leigh syndrome

A

Pyruvate dehydrogenase deficiency

Tx - thiamine and ketogenic diet

  • Males = mild mutations (severe mutations lethal)-> leigh syndrome, normal brain structure
  • Females = het for severe mutations -> structural abnormalities, normal lactate (X inactivation)
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117
Q

POLG related disease

A

Alpers syndrome

  • Multisystemic with many neurologicalm manifestations
  • Polymerase Gamma
  • VPA use can precipitate liver failure
  • mtDNA depletion + Complesed I/III/IV deficiency
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118
Q

Steroid resistant nephrotic syndrome

A

CoQ10 synthesis defect

  • ADCK4, PDSS2, COQ2, COQ6
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119
Q

Non-compaction cardiomyopathy, neutropenia, myopathy + high 3-methylglutaconic acid

A

Barth syndrome

TAZ (X Linked)

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120
Q

What does CblJ and CblF deficiency cause?

A

Combined HCy and MMA

  • Cbl transport out of lysosome into cytosol where CblC is
  • Serum B12 levels low - but NOT B12 deficiency
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121
Q

What does Methylmalonyl CoA Epimerase deficiency cause?

A

MMA and PA

  • Slight elevation in MMA (only D-Methylmalonyl=CoA high) and proximal buildup of PA + 2-methylcitrate (secondary PA metabolite)
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122
Q

What should be ruled out if baby presents with NBS high MMA but no mutation is found?

A

Maternal B12 deficiency

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123
Q

What are the first steps after diagnosing sick child w/ MMA/PA?

A
  • Determine B12 resonsiveness with hydroxocolbalamin
  • Can try biotin if PA suspected (PA Carboxylase)
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124
Q

Bulls eye maculopathy

A

CblC (rarely CblD)

Bulls eye maculopathy can progress to RP and optic nerve atrophy despite treatment

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125
Q

Macocytic anemia, pancytopenia, high MMA, high HCy

A

Transcobalamin 2 deficiency

TCN2

  • Treat with OH-Colbalamin injections
  • Looks like neonatal leukemia/SCID
  • TC2 colbalmin receptor deficiency tends to be milder/transient
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126
Q

What Cbl defects can have low B12 levels?

A

Cbl J and Cbl F

  • abnormal lysosomal efflux
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127
Q

What is CblX?

A

HCFC1 and epi-cblC mutations

HCFC1 is X-linked

  • Promoters/regulators of CblC expression
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128
Q

What is the first clinical sign of MSUD?

A

Maple syrup odor in ceruloplasmin

129
Q

most common creatine disorder

A

Creatine transporder deficiency

XL - transports GAA (produced in liver) into brain/muscle

  • autisim
  • 1-2% of ID in males
  • variable sieizures
  • usually achieve motor sckills, may have decreased muscle bulk
130
Q

Arginine Glycine Amidinotransferase Deficiency

A

Rarest Creatine synthesis disorder

  • Arginine + glycine -> Ornithine (negative feedback) + GAA
  • Static encephalopathy
  • Seizures rare, no regression
131
Q

AGAT vs GAMT vs CT

A

AGAT tends to be static with no regression, also less seizures; may have FTT

GAMT tends to have progression, intractable epilepsy, and movement d/o, no FTT

Creatine transporter (XL) usually delay + autism (may have FTT)

132
Q

Low GAA, Low/nl Creatine

A

Arginine Glycine Amidinotransferase deficiency

  • static encephalopathy, no regression, rare seizures
133
Q

high GAA, low/nl creatine

A

Guanidinoacetate methyltransferase deficiency

  • Epilepsy, regression, movement disorder
134
Q

Normal GAA and Creatine.

Urine Creatine/Creatinine ratio > 1600

A

XL Creatine Transporder Deficiency

ID/Autism

  • Creatine cannot get into musclae cells were it gets converted into createnine
135
Q

Treatment for creatine synthesis defects

A

AGAT/GAMT -> Creatine monophosphate supplement

GAMT -> Arginine restriction, ornithine supplement to decrease production of GAA (Ornithine is inhibitor of AGAT)

Creatine Transport - no therapy

136
Q

High Hypoxanthine, Xanthine, and Uric Acid

A

Lesch Nyhan (HGPRT)

Hypoxanthine Guanine Phosphoribosyltransferase deficiency

  • Hypoxanthine and Guanine recycline defect
  • Neuro + Gout + nephrolithiasis
137
Q

High succinyladenosine (S-Adenosine) and SAICA Riboside

A

Adenylosuccinase/Adenylosuccinate lyase deficiency

ADSL

Seizure/ID

138
Q

What are the main phenotypes of purine metabolism disorders?

A

Neurological

Immunological

Gout/Renal Failure

139
Q

High inosine and guanosine, low uric acid

A

Purine Nucleoside Phosphorylase Deficiency

PNP

Neuro + immunodeficiency

140
Q

High adenosine + adenine

Immunodeficiency

A

Adenosine Deaminase Deficiency

ADA

  • NBS TRECs
  • SCID
  • Enzyme replacment (PEG-ADA)
141
Q

Name 3 purine disorders that cause primarily nephrolithiasis

A

PRPPS - Phosphoribosyl-pyrophosphate synthetase superactivity (high urine acid)

XO - Xanthine Oxidase (high xanthing, hypoxanthine, low uric acid (high in HGPRT))

APRT - Adenine phosphoribosyltransferase deficiency (high adenine)

142
Q

What is cyclic pyranopterin monophosphate used to treat?

A

Molybdenum cofactor deficiency (cPMP)

143
Q

Which purine disorders present with SCID?

A

ADA - high adenosine, adenine

PNP (PNP = neuro + scid) - high inosine, guanosine

144
Q

High xanthine, hypoxanthine

Low uric acid

A
  • Xanthine Oxidase deficiency - renal stones
  • Molybdenum Cofactor deficiency - neuro, lens dyslocation

(Xanthine/Hypoxanthine high in HGPRT, but urine acid also high)

145
Q

High succinyladenosine

A

ADSL deficiency

  • neuro
146
Q

High adenine, normal adenosine

A

APRT deficiency

  • nephrolithiasis

(if adenosine also high then ADA)

147
Q

High uric acid and hypoxanthine

A

PRP Superactivity

  • gout + stones
148
Q

Main neurological Purine disorders?

A

Molybdenum cofactor (High xanthine, hypoxanthine, low uric acid)

ADSL (Succinyladenosine)

HGPRT (high xanthine, hypoxanthine, uric acid)

149
Q

anemia + orotic aciduria

A

Hereditary orotic aciduria

UMPS

Uridine monophosphate synthease deficiency

  • Anemia unresponsive to B12, folate, iron
150
Q

High uracil and thymine

A

Dihydropyrimidine Dehydrogenase Deficiency

Neuro, FTT, epilepsy

  • may be asymptomatic, 5FU toxicity
151
Q

high dihydrouricil, dihydrothymine, uracil, thymine

A

Dihydrophrimidinase deficiency

Asymptomatic, may be neuro, epilepsy

152
Q

mitochondrial disease with high thymidine levels

A

MNGIE

Thymidine phosphorylase deficiency

153
Q

High dihydrouracil, dihydrothymine, urediopropionic and urediosiobutyric acid

A

Ureidopropionase Deficiency

UPB1

  • asympatomatic vs neuro + seizure + dystonia
154
Q

Low dopamine and VMA, high 3-o-methyldopa

A

AADC deficiency

155
Q

Low Homovanillic acid/5-HIAA ratio

A

Tyrosine hydroxylase deficiency

(Tryptophan hydroxylase is normal)

156
Q

X Linked monoaminemetabolism defect

A

MAOD

  • usually mild ID with aggressive behavior
157
Q

high CSF and plasma GABA

hypomyelination, movement disorder, EIEE

A

GABA transaminase deficiency

ABAT gene

  • 2-pyrrolidinone biomarker
158
Q

High 4-hydroxyisobutyric acid, high GABA

A

Succinic Semialdehyde Dehydrogenase Deficiency

Neurodevelopmental, EIEE

159
Q

Why do SLOS patients have dysmorphology?

A

Cholestrol and 7DHC are activators of SHH

SLOS -> low cholesterol, high 7DHC

160
Q

RCDP + ichthyosis, coarse hair

A

XL CDP -> male lethal

Sterol 7.8 isomerase

161
Q

High Lathosterol

A

Lathosterolosis

SLOS like

Sterol 5 desaturase

162
Q

high desmosterol

A

Desmosterolosis

SLOS like

DHCR24

163
Q

SLOS like cholesterol disorders

A

SLOS - DHCR7

Lathosterolosis - SC5DL (5 desaturase)

Desmosterolosis - DHCR 24

  • squaline synthase deficiency also looks similar (rare) - FDFT1
164
Q

High mevalonic acid

A

Mevalonic Kinase (MVK) deficiency

  • High IgD w/ recurrent fevers
  • Dysmorphic, RP, Ataxia + immune
165
Q

High lanosterol and dihydrolanosterol

A

Antley Bixler

POR/CYP450

166
Q

high sitosterol, campesterol

A

Sitosterolemia- Sterol transporter defect

ACBG5, ACBG8 (AR)

Increased plant sterol absorption

  • Xanthomas (including buttock), artherosclerosis, splenomegaly, arthralgies
167
Q

Cholesterol disorders with primary severe skin manifestations

A

SC4MOL - sterol C4 methyoxidase (MSMO1)

CHILD syndrome - 4-demethylase (NSDHL)

  • high 4 methylsterols
168
Q

Where are NPC1 and NPC2 located?

A

NPC is disorder of cellular cholestrol trafficking -> accumulation of cholesterol esters in lysosomes

NPC1 - late endosomal membrane protein

NPC2 - lysosomal cholesterol binding protein

169
Q

3 presentations of NPC

A

1) Hydrops
2) neonatal liver disease
3) late onset neurological + hepatomegaly

170
Q

“sea blue histiocytes”

Positive Filipin Stain

171
Q

diarrhea, cataracts, DD, hepatitis, xanthomas, neurodegeneration

High Cholestanol

A

CTX

Sterol-27 hydroxylase (CYP27A1)

  • Bile acid metabolism block -> buildup of cholestanol in CNS
  • Treat with chenodeoxycholenic acid
172
Q

Low LDL cholesterol and neurological deterioation

A

Abetalipoproteinemia

MTTP (microsomal triglyceride transfer protein)

173
Q

Sebelipase Alfa

A

ERT for Lysosomal Acid Lipase Deficiency

Wollman or Cholesterol Ester Storage disease

  • LSD with adrenal calcifications, microvesicular steatosis
174
Q

Orange Tonsils

A

Tangier Disease

ABCA1

low HDL

175
Q

acrodermatitis, diarrhea, alopecia, FTT

A

Acrodermatitis enteropathica

Zinc deficiency, Transporter defect (ZIP4 or ZnT2)

ZIP4- Symptom onset when weened from breastmilk

ZnT2 - Symptom onset when baby is on breastmilk

176
Q

ATP7A deficiency

A

Menkes

X-linked

Enterocyte Cu transporter -> deficiency

177
Q

ATP7B deficiency

A

Wilson’s

Liver/CNS Cu secretory protein

  • Liver overloaded with Cu, serum Cu low, urine Cu high
178
Q

Polycythemia, Parkinsonsim, Dystonia

A

Manganese toxity (and transporter defects)

SLC30A10 - + liver disease (cannot leave liver)

SLC39A14 - no liver disease (not absorped by liver)

179
Q

What metabolites tell you about cytoplasmic NADH/NAD ratio?

A

Lactate/pyruvate

180
Q

What does 3-hydroxybutyrate/acetoacetate ratio tell you?

A

Intramitochondrial NADH/NAD+ ratio

181
Q

high deoxyuridine, deoxythymidine levels

A

MNGIE

Thymidine Phosphorylase deficiency

182
Q

high thiosulfate, hydrogen sulfide, ethylmalonic acid, C4/C5 acyl-carnitines

A

Ethylmalonic encephalopathy

ETHE1 persulfide dioxygenase

183
Q

Normal complex 1-4 activity, low combined complex 2-3 and 1-3 activity

A

CoQ10 deficiency

184
Q

What are FGF21 and GDF15 used for?

A

Markers of mitochondrial dysfunction

  • useful for mtDNA maintenance/depletion/translation disorders
  • Not useful for complex subunit disorders
185
Q

SURF1 mutation cause what disease? What mito complex finding?

A

Leigh syndrome

isolated complex IV decrease (Complex IV assembly factor)

186
Q

What mito complex pattern do you see in POLG?

A

Decreased 1, 3, and 4

(complex 2 is nuclear encoded)

187
Q

Treatment for MELAS

A

Arginine, Citrulline, Taurine (Natural Taurio-methyl uridine modification is impaired by 3243 mutation)

188
Q

How do you treat NKH?

A

Sodium Benzoate (conjugates with glycine to form hippurate)

NMDA blockade

189
Q

What is the end product of AA transamination?

A

Ammonia (NH3) and a-ketoacid (R-CO-COOH)

190
Q

Why is lysine high when ammonia is high?

A

2KG used to synthesize glutamate instead of saccharopine

191
Q

What is rate limiting step of urea cycle?

A

NAGS -> senses glutamate levels (protein breakdown product)

192
Q

Carbohydrate induced hyperammonemia

A

Citrin deficiency

  • High protein, low carb diet
193
Q

hyperammonemia, diarrhea, PTT, pneumonitis

PAA: Low arginine, ornithine, lysine

UAA: high arginine, ornithine, lysine

  • high LDH/ferritin
A

LPI

SLC7A7 - dibasic AA transporter

+ macrophage activation syndrome

194
Q

What is the name for organic acids with the following C chain lengths:

2, 3, 4, 5, 6

A

2 - acetic

3 - propionic

4 - butyric

5 - valeric

6 - caproic

195
Q

What is the name for dicarboxylic organic acids with the following C chain lengths:

2, 3, 4, 5, 6

A

2 - oxalic

3 - malonic

4- succinic

5- glutaric

6 - adipic

196
Q

what is the cofactor used by enzyme that causes PA?

A

Biotin

PA = propionyl-CoA carboxylase deficiency

197
Q

C5DC

A

Glutarylcarnitine

  • GA1
198
Q

C5

A

Isovalerocarnitine

IVA

199
Q

Boiled cabbage odor

A

Tyrosinemia type I

FAH deficiency

200
Q

Treatment for ALD7A1 (antiquitin) deficiency

A

Pyrodoxine 5 Phosphate

B6 dependent epilepsy

201
Q

methylcitric acid

202
Q

methylcrotonylglycine

A

3MCC

Also seen in multiple carboxylase deficiency

203
Q

Tiglylglycine

A

PA, HSD10, 3-ketothiolase

204
Q

Most common cause of adipic acid elevation

205
Q

Alanine/lysine > 3.0

A

mitochondrial dysfunction

206
Q

3-hydroxy-3-methylglutaric acid

A

HMG-CoA Lyase deficiency

207
Q

2-keto-isovaleric and 2 hydroxy-isovaleric acid

A

MSUD

  • 2-keto acids = MSUD
208
Q

3-methylglutaconic acid

A

HMG-CoA lyase deficiency

Barth syndrome + other mito membranse disorders

209
Q

methylsuccinic acid

A

Ethylmalonic encephalopathy

210
Q

very high ethylmalonic and adipic acid in urine

A

Ethylmalonic aciduria

211
Q

5-oxoproline

A

Glutathione synthetase deficiency

212
Q

4-OH-butyric acid

A

Succinic semialdehyde dehydrogenase deficiency (SSADH)

213
Q

4-hydroxycyclohexylacetic acid

A

Hawkinsonuria - 4OHphenylpyruvate dioxygenase deficiency

  • metabolic acidosis + tyrosinemia
  • Resolve in first year of life
214
Q

What is C5OH?

A

Hydroxyisovaleryl-CoA

  • B-ketothiolase
  • HMC-CoA Lyase
  • 3MCC
  • Multiple carboxylase deficiency
215
Q

C4DC

A

C4DC = succinyl-CoA

  • SUCLA2 (Succinyl-CoA synthetase) deficiency
216
Q

Postprandial hypoglycemia

A

Hyperinsulinism or HFI

217
Q

Hypoglycemia after 3-12hr fast

A

Glycogen or gluconeogenesis defect

218
Q

Hypoglycemia after 12 hour fast

A

FAO defect (low ketones) or ketotic hypoglycemia

219
Q

GSDs that predominant present as liver disease (without hypoglycemia)

A

Type IV (Branching enzyme)

Type VI (liver phsophorylase/phosphorylase kinase)

220
Q

GALT Q188R

A

Classical galactosemia, caucasians

221
Q

GALT S135L

A

Classic galactosemia, African Americans

222
Q

GALT N314D

A

Duarte variant

223
Q

GALT K285N

A

Variant galactosemia

224
Q

Adolase B deficiency

225
Q

How to tell apart SBCAD from Ethylmalonic encephalopathy?

A

SBCAD: EMA, methylsuccinic acid, C4

ETHE: EMA, adipic acid, C4

226
Q

What does ACAD9 cause?

A

mito complex I deficiency

  • Cardiomyopathy, neuro, muscle
  • May have signs of FAOD and liver failure
227
Q

Bulbar palsy, optic atrophy, SNHL, neuropathy, respiratory failure

A

Brown-Vialetto-Van Laere syndrome

Most common Riboflavin transporter defect

SLC42A3

228
Q

Name 4 glucose transporters

A

SGLT1 - Glu+Galactose malabsorption -> profuse diarrhea

SGLT2 - renal glucosuria

GLUT1 - epilepsy

GLUT2 - fanconi bickel (GSD like)

229
Q

Hyperammonemia, hypoglycemia requiring high GIR

A

Glutamate Dehydrogenase (GDH)

  • Hyperinsulinism + hyperammonemia
230
Q

FAOD with hyperinsulinism

231
Q

What biochemical marker distinguished GSD1 from GSD3?

A

Lactate. GSD1 is also gluconeogenesis defect so lactate elevated when fasting; this is not true in GSD3

232
Q

What metabolites tell you NAPH/NAD+ in mitochondria?

A

3OH-butyrate/Acetoacetate

Lactate/pyruvate = cytoplasmic

233
Q

High lactate/pyruvate

Low 3OH Butryate/acetoacetate

A

Pyruvate carboxylase deficiency

Disconnect between mito and cytoplasmic NADH/NAD+ (redox) state

234
Q

Lactic acidosis with low lactate/pyruvate ratio (<12)

A

Secondary lactic acidemia

Pyruvate dehydrogenase (Pyruvate high)

Pyruvate transporter

Thiamine deficiency (PDH affected)

235
Q

Lactic acidosis during fasting

A

Gluconeogenesis (FBPase or G6Pase - GSD1)

FAOD (secondary gluconeogenesis impariment)

236
Q

Postprantial lactic acidosis

A

Inability to store glucose -> GSD0, GSDIII, GSD VI

Glucose metabolism -> PDH, Pyruvate transporter (normal L/P ratio)

-> PC, ETC disease (high L/P)

237
Q

Postprantial lactic acidosis and ketosis

high L/P ratio

Hyperammonemia with low glutamine

High citrulline, proline, lysine

A

Pyruvate Carboxylase

Postprandial ketosis since TCA cycle slowed and acetoacetate is used to synthesize ketones instead

  • Low spartate production -> Urea cycle block
238
Q

Fasting ketotic hypoglycemia + high postprandial lactate

A

GSD0 or GSD3

239
Q

LSD due to protein associated with autophagolysoomal fusion/pH control

A

Neuronal Ceroid Lipofuscinoses

240
Q

LSD due to cholesterol binding protein

241
Q

sebelipase alfa

A

ERT for Wolman/cholesterol ester storage disease

sebelipase

242
Q

Alglucosidase alfa

A

ERT for pompe

alglucosidase

243
Q

Imiglucerase, Velaglucerase, Taliglucerase

A

ERT for Gaucher (glucocerebrosidase)

  • glucerase
244
Q

agalsidase

A

ERT for fabry (alpha galactosidase)

agalsidase

245
Q

PEX7

A

RCDP type 1 (low plasmalogen)

  • Type 1 also high phytanic acid
246
Q

NBS for C5OH

A

BCAA pathway intermeidates (Leu and Ile)

+ holocarboxylase and HMG-Coa Lyase

247
Q

alpha aminoadipic aciduria

A

COOH-CH(NH2)3-COOH

Lysine/tryptophan breakdown intermediate; metabolized to acetoacetylcoa via glutaryl coa

  • DD/ acidosis vs non-disease
248
Q

treatment for OAT

A

Pyridoxine, arginine restriction

249
Q

low homocysteine, high methionine

A

MAT - benign vs CNS

GNMT (methyltransferase) - hepatomegaly, high LFTs

SAHH, AHCY (Adenosylhomocysteinase) - MR, FTT

250
Q

4-OH Phentyllactic, 4OH-phentylpyruvic, and 4OH phenylacetic acid

A

Tyrosinemia - 4OH phenyl-acids elevated in all three types

TAT, 4HPPD, FAH

251
Q

4OH phenyl acids + 2-L-cystein-S-yl-1,4-dihydroxycyclhex-5-en-1-yl acetic acid

A

2-L-cystein-S-yl-1,4-dihydroxycyclhex-5-en-1-yl acetic acid = Hawkinsin

4-hydroxyphenylpyruvate dioxygenase deficiency

Normal -> metabolic acidosis + FTT

252
Q

BH4 defects with high Phe

A

PTPS, PCD, DHPR

253
Q

BH4 defect wiht high primapterin

254
Q

BH4 defect with high biopterin

255
Q

high 3OMD

256
Q

High HVA

A

Dopamine B Hydroxylase Def

257
Q

PAA profile for SUOX

A

High taurine, low cystine

258
Q

Precursor to sulfur AAs

A

Methionine

259
Q

High a-aminoadipic semialdehyde and pipecolic acid

A

antiquitin

A-aminoadipic semialddehyde dehydrogenase deficinecy

Pyridoxine dependent epilepsy

260
Q

High L-Dopa, 3 methoxytyrosine, Thr, Glycine

Low HVA, 5-hydroxyindoleacetic acid

UOA: vanillactate acid

A

PNPO

Pyridoxal-5-phosphate oxidase deficiency

Pyridocal-phosphate dependent epilepsy + cerebral atrophy

biochem looks like AADC + theronine dehydratase + glycine cleavage sysem)

261
Q

Butyrylcarnitine

Ethylmalonic acid

A

SCAD

ACADS gene

Butyrylcarnitine = C4 (ddx isobutyrylcarnitine in IBDH deficiency)

EMA ddx MADD, EE, mito, litchee, jamaican vomiting sickness

262
Q

Which AAs are NORMAL in urine of Hartnup disease?

A

SLC6A19 - neutral AA transporter

Glycine, Proline, Hydroxyproline are normal

263
Q

Urine AA: Cystine, Lysine, ortnithine, argnine

A

Cystinuria

SLC3A1

-

264
Q

PAA: Low Lys, Arg, Orn

UAA: High Lys, Arg, Orn

A

LPI

  • cationic transporter SLC7A7

Lys, Arg, Orn

265
Q

UOA: Thymine and uracil

A

Dihydropyrimidine dehytogenase deficiency

  • 5FU toxicity, MR, microcephaly, FTT
266
Q

4 OH Butyric acid

A

Succinic Semialdehyde Dehydrogenase deficiency

ALDH5A1

Succinic semialdehyde cannot be tunred into succinic acid, so becomes 4OHB instead

267
Q

high erythritol, arabitol, ribitol

A

Transaldolase

TALDO1

Hydrops vs severe liver disease

268
Q

XL Sideroblastic anemia

A

ALA synthase deficiency

ALAS superactivity = prophyria

269
Q

Stool isocoproporphyrin

A

UROD

Porphyria cutaneous tarda or heptoerythropoetic porphyria

270
Q

Low serum Cu and Ceruloplasmin, abnormal plasma catecholamines

A

Menkes (ATP7A)

271
Q

Low serum Cu and ceruloplasmin, high urinary copper

A

Wilsons (ATP7B)

272
Q

Low serum Cu and absent ceruloplasmin, lower iron, high ferritin

A

Aceruloplasminemia (CP gene)

Brain iron accumulation

273
Q

petechiae, acrocyanosis, diarrhea, epilepsy, movement d/o

A

Ethylmalonic encephalopathy

ETHE1

High EMA and Methylsuccinic acid

High C4 and C5

274
Q

4 enzymes that require biotin

A

Pyruvate carboxylase (Mito)

Propionayl-CoA carboxylase (PA)

B-methylcortonyl CoA Carboxylase (3MCC)

Acetyl-CoA Carboxylase

275
Q

High C5OH, high 3-OH IVA, 3 methylcrotonylglycine, low carnitine

A

3MCC

  • leucine metabolism
276
Q

4 disorders of Leu breakdown

A

MSUD

IVA - 3IVA, C5

3MCC - 3MCG, 3IVA, C5OH

3MGC - 3MCG, 3MGA, 3IVA, C5OH, C6DC

277
Q

C3 + C4DC

A

Think MMA/ SUCLA

278
Q

Lamellar lipoproteins

A

LCAT

low HDL

279
Q

Frederickson Lipid Classification

A

CLIVE

I - Chylo

II - LDL

III - IDL (VLDL remnant/ B- VLDL)

IV - VLDL

V - Everything else

280
Q

How do you tell apart abetalipoproteinemia from familial hypobetalipoproteinemia

A

Carriers for a-beta (MTTP - microsomal TG transfer protein) do NOT have hypobetalipidemia;

hypobetalipoproteinemia (APOB) do have hypobetalipidemia.

281
Q

acanthocytosis + steatorrhea; low LDL and TG; carriers have low betalipoproteins

A

Familial hypobetaliporptoteinemia

APOB gene

  • Mostly truncating variants
  • Unable to form chylomicrons from dietary fats, Vit E absorption
282
Q

acanthocytosis + steatorrhea; Low LDL and TG; carriers have normal betalipoproteins

A

Abetalipoproteinemia

MTTP

  • Microsomaltransfer protein
  • Carriers have no phenotype

Unablte to form chylomicrons from dietary fat - vitE def

283
Q

Low LDL and TG, Apo A1 and ApoB

Lipid laden enterocytes

A

Chylomicron retention disease

SAR1B -> abnormal trafficking of chylomicrons within enterocytes

Fat malabsorption, FTT, Vit deficiency

284
Q

high Chylomicrons, Cholesterol, TG very high

A

Lipoprotein lipase (LPL) deficiency vs ApoC2

AR, carriers have familial combined hyperlipidemia

  • Abd pain/pancreatitis; need low fat diet
  • not associated with CAD (hepatic lipase has arteriopathy)
285
Q

high ACE, tartrate-resistant acid phosphatase (TRAP), and chitotriosidase

A

Gaucher

Glucocerebrosidase def

N370S, L444P

286
Q

high cit, argninine, theronine

High ammonia, galactose, AFP

A

Citrin deficiency

  • supplement argnine/aspartate, high protein diet
287
Q

how do you distinguish hypoglycemia caused by hyperinsulinism from FAOD?

A

Both are non-ketotic

  • Free FA high in FAOD
  • Free FA (lipolysis) low in hyperinsulin
288
Q

Mousy odor

289
Q

High ammonia, normal citrulline, high lactate

A

Pyruvate carboxylase

290
Q

Ways to distinguish GSDI from other GSDs

A

High uric acid and lactic acid in GSD1

Moderate ketosis in GSDI - higher ketones in GSD0, III, IV, and IX

Nephromegaly most prominent in GSD1

Transient LFTs in GSD1 - Cirrhosis in GSD IV

291
Q

GSDs with postprandial hyperglycemia

A

GSD0

Fanconi-Bickel

292
Q

GSDs with normal lactate

A

GSD III

Only elevated postprandially in GSD VI and GSD IX

293
Q

Jaundice, hepatosplenomegaly, lymphadenopathy, anemia

A

Mevalonic Aciduria

MVK deficiency (Pre-squalene)

  • alleleic with hyper IgD

+ DD

294
Q

Male cat urine smell

A

3-OH IVA

3MCC, multiple carboxylase deficiency

295
Q

Rancid butter smell

A

Tyrosinemia type 1

  • Also cabbage
296
Q

Sulfur smell in urine

A

Cystinuria and Tyr type 1 (methionine)

297
Q

high alk phos -> IEMs

A

bile acid synthesis disorders, GPI anchor disorders

298
Q

IEMs with hypothyroidism

A

Mito, CDG, TFP

299
Q

MMA vs PA

A

PA has more cardiomyopathy

MMA has more renal

300
Q

NBS: high C5

A

IVA vs enthylmalonic encephalopathy vs SBCAD (non disease)

301
Q

etheylmalonic acid + butyrylcarnitine, butyrylglycine

302
Q

methylacritic acid

A

hydratase or 2-hydroxyisubtyryl-Coa Hydrolase deficiency

Val/Ile metabolism

Neuro + cardiomyopathy + hepatomegaly

Hydratase (ECHS1) - 2-methyl-2,3-dihydroxybutryate, C4

HIBCH - C4OH (hydrolase deficiency)

303
Q

MMA + 3OH-isobutyric acid

A

MMA semialdehyde dehydrogenase

ALDH6A1

  • Val metabolism
  • non-disease (found on NBS)
304
Q

Hydroxyphntylpyruvate dioxygenase

A

HPD -> Tyr type 3 or Hawkinsonuria (c.722A>G)

  • benign
305
Q

Isolated hypermethionine

A

Mudd’s disease

MAT

  • Cabbage odor
306
Q

which methionine -> hcy disorder does not have ID

A

MAT and GNMT

SAMH and ADK have ID

307
Q

urine uroporphyrin, tool isocoproporphyrin

A

Porphyria Cutanea Tarda

308
Q

disorders treatable with uridine supplement

A

Proximal pyrimidine synthesis

UMPS, DHODH, CAD

309
Q

HEXA R247W (739 C>T), R249W (745 C>T)

A

Tay Sachs peudodeficiency alleles

310
Q

SUMF1

A

Multiple sulfatase defiency

MLD + MPS + ichthyosis

311
Q

C5OH + C6DC

A

HMG-CoA Lyase

312
Q

C5OH and C5:1

A

Beta Keto Thiolase

313
Q

Hydrops with MPS

A

MPS 7 -> sly

314
Q

What metabolite do you need HPLC to see

A

Homocitrulline

315
Q

LSD with interstitial lung disease

A

NP - B (acid sphingomyelinase)

316
Q

HSM + HLH

A

LPI

High Orn, Arg, Lys

317
Q

HSM + hemolytic anemia

A

Transaldolase

318
Q

HSM + recurrent inflammation

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