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Royal College Peds 2021 > Metabolic Sid > Flashcards

Metabolic Sid Flashcards

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1
Q

How do you investigate a child with a suspected metabolic disease?

A
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2
Q

What are the metabolic conditions tested for in the USA?

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3
Q

What are the DDX of a newborn with high NH3?

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4
Q

What are the detailed list of DDx for newborns with high NH3?

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5
Q

How do you investigate for the different causes for high NH3?

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6
Q

What non metabolic tests should you do with newborn with suspected defect of the urea cycle enzymes.?

A

Routine laboratory studies show no specific findings:

  • Blood urea nitrogen is usually low
  • serum pH is usually normal or mildly elevated
  • mild increases in ALT, AST
  • r/o sepsis
  • Neuroimaging may reveal cerebral edema.
  • Autopsy is usually unremarkable.
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7
Q

What are the Clinical Indications for Measuring NH3?

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8
Q

What do you look for on history with high NH3?

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9
Q

Exam findings with high NH3?

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10
Q

What investigation approach do you follow with high NH3?

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11
Q

How do you differentiate the DDX for raised NH3 by lab tests?

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12
Q

How do you manage high NH3 from the pathways?

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13
Q

What is the Acute Management of UCDs?

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14
Q

Chronic Management of UCDs?

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15
Q

When to suspect a metabolic condition in a non neonate?

A

Neuro:

mental retardation, developmental delay or regression

motor deficit, convulsions; mental deterioration/coma

Gastro:

unusual odor (esp when unwell),unexplained vomiting, hepatomegaly

Renal:

unexplained acidosis, renal stones

Other:

muscle weak-ness or cardiomyopathy.

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16
Q

What do you know about the following Metabolic Disorders ?

urea cycle disorders

organic acidemias

fatty acid oxygidation

A
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17
Q

What enzymes defects are involved in Galactosemia?

A

Elevated level of galactose in the blood and is found in

3 distinct enzyme defects:

  1. galactose-1-phosphate uridyl transferase (G1PUT)

complete (classic galactosemia) and partial transferase deficiency (more common, but milder, detected by Guthrie)

  1. galactokinase
  2. uridine diphosphate galactose-4-epimerase.

The term galactosemia, generally designates the transferase deficiency.

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18
Q

Diagnosis for Galactosemia?

A

Urine:

  1. Glucose & reducing substance in several specimens -b milk, formula or (Clinitest (has galactose, others) Clinistix -only glucose)
  2. Amino aciduria due to proximal renal tubular syndrome

3. Check for UTI- E Coli

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19
Q

Clincial features of G1PUT Galactosemia?

A

_Toxin is Galactose 1 phosphate..!!**_

1. Neuro:

Brain: seizures, lethargy, mental retardation, Developmental delay, speech problems, abnormal motor functionPseudotumor cerebri -bulging fontanel

Eye: nuclear cataracts, vitreous hemorrhage,

2. Gastro:

-General: , poor feeding/vomiting, FTT

Liver: Jaundice, hepatomegaly/hepatic failure, liver cirrhosis, ascites, splenomegaly,

3. Renal/Metabolic: Renal failure- renal tubular problem (aminoaciduria), hypoglycemia,

  1. MSK- Decreased bone mineral density—

5. Heme: Bleeding and coagulopathy (secondary to liver failure)—

6 Endo: Growth delay, primary ammenorrhea, premature ovarian failure

7. Sepsis (Escherichia coli, Klebsiella, Enterobacter, Staphylococcus, Beta-streptococcus, Streptococcus faecalis- they all use galactose as their substrate, EColi sits in kidney)

N.B. . Death from: liver/kidney failure and sepsis

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20
Q

What is the definitive test for Galactosemia G1PUT?

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21
Q

What is the management of Galactosemia G1PUT?

A

Acute decompensation management principles

  1. ABCs
  2. Provide-iv dextrose
  3. Treat/eliminate inciting factor (galactose)
  4. Monitor for acute complications
    a. Hypoglycemia
    b. Hyperbilirubinemia
    c. Liver failure
    d. Sepsis
    e. Hyperammonemia ( Liver failure, less high than urea cycle)
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22
Q

What are the trigger factors for Disorders of Mitochondrial Fatty Acid β-Oxidation?

A
  1. prolonged periods of starvation
  2. gastrointestinal illness-reduced caloric intake
  3. increased energy consumption in febrile illness
  4. important fuels for skeletal muscle and heart

N.B. body switches from using predominantly carbohydrate to

predominantly fat as its major fuel in the 1st 3 scenarios

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23
Q

How do fatty acid disorders present?

A

Affect tissues with a high β-oxidation flux including liver, skeletal, and heart

Timing:

Normal initially, then present in infancy/early childhood during prolonged fast

Commonest:

  1. Coma, fits (like Reyes Synd) and “non ketotic hypoglycemia” (with fasting)…may get SIDS..
  2. Acute cardiorespiratory collapse, Chronic cardiomyopathy , muscle weakness and hepatomegaly
  3. Exercise induced acute rhabdomyolysis.

4. LCFAOD may present with rhabdomyolysis, cardiomyopathy and liver failure (not SCAD or MCAD)

Rare:

  1. Progressive retinal degeneration, peripheral neuropathy and chronic liver disease in LCHAD and TFP deficiency.
  2. In LCHAD & TFP a homozygous fetus can lead to a heterozygote mother -acute fatty liver of pregnancy or PET + HELLP
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24
Q

What are the common fatty acid disorders?

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25
Q

What is the “EASY” 2 part list for FAOD’s ?

A

1. CHAIN:

Short: SCAD

Medium: MCAD

Long: VLCAD

2. MEMBRANE:

Plasma: Carnitine uptake deficiency

Mitochondrion: CPT1

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26
Q

What are the clincial features of the fatty acid oxidation disorders?

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27
Q

What are the lab features in MCAD and FAODs?

A

1. Blood:

a. Basic: CBC, Gluc (hypoglycemia), lytes, lactate and CPK, bld gas, ketones (low)

b. Liver: raised ALT, AST, PT, PTT & NH3
c. metabolic: plasma carnitine + acylcarnitine levels
d. Guthrie: raised acylcarnitines in filter paper blood spots.
2. Urine:
a. In fasting- elevated levels of mediumchain dicarboxylic acids
b. Ketones
c. MS analysis of Urine organic acids, acylglycine

3. Diagnosis

a. common A985G mutation
b. measurement of specific enzyme activity

c Plasma acylcarnitine and plasma carnitine (free and total)

4. Pathology:

a. Liver biopsy -steatosis The diagnosis of FAODs even
b. postmortem for genetic counselling and evaluation of siblings

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28
Q

How do you manage a child in crisis with FAOD?

A
  1. iv 10% dextrose (12-15 mg/kg/min ) to treat hypoglycemia+ suppress lipolysis as
  2. Avoid fasting >10-12 hr.
  3. Restricting dietary fat or treatment with carnitine is controversial. Long-chain fat, however, needs to be restricted in severe long-chain FAODs and substituted by medium-chain triglycerides
  4. Hospital admission is recommended for procedures that would require the patients to take nothing orally for >8 h, especially if less than 1 year of age.
  5. Carnitine is undisputedly effective in patients with carnitine transporter deficiency
  6. Liver transplantation may be the ultimate consideration if there is NO evidence of neurological disease or other systemic involvement that may impair recovery and return to baseline function
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29
Q

What is the prognosis of children with FAOD?

A

1. DEATH:

a. 25% of unrecognized patients may die during their 1st attack of illness.
b. Often Hx history of sibling death due to unrecognized MCAD deficiency.

2. Brain injury:

a. +/- permanent brain injury 2” to hypoglycemia.

b. The prognosis for survivors without brain damage is excellent because cognitive impairment or cardiomyopathy does not occur in MCAD deficiency.

3. Increasing age:

a. Muscle pain and reduced exercise tolerance may become evident with increasing age.
b. Fasting tolerance improves with age and the risk of illness decreases.

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30
Q

What are the most common types of FAOD?

A
  1. MCAD- most common
  2. Very Long Chain Acyl CoA Dehydrogenase (VLCAD) VLCAD 2nd most common, usually more severely affected than those with MCAD deficiency, presenting earlier in infancy and having more chronic problems with muscle weakness or episodes of muscle pain and rhabdomyolysis
  3. Short-Chain Acyl CoA Dehydrogenase (SCAD) Deficiency - mild
  4. Long-Chain 3-Hydroxyacyl CoA Dehydrogenase
    * *(LCHAD)/Mitochondrial Trifunctional Protein (TFP)** Deficiency- more severe than MCAD
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31
Q

Case summary of child with FAOD

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32
Q

Where do the Glycogen Storage diseases fit on the glycogen pathway?

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33
Q

What is the role of insulin and glucagon on the glycogen pathways?

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34
Q

What is the clinical picture in Von Gierke’s disease?

Hepatic (GSD1a) - Von Gierke disease primarily cause fasting hypoglycemia,

Muscular (GSD V)- Mc Mrdles result in recurrent rhabdomyolysis.

A
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35
Q

What is the clinical picture in Cori disease?

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36
Q

What is the clinical picture in McArdlea and Her’s disease?

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37
Q

What is the clinical picture in Anderson’s disease?

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38
Q

What is the clinical picture in Pompe’s disease?

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39
Q

What are the features and management of Von Gierke Type GSD 1a?

A

Deficiency in the enzyme glucose-6-phosphatase,

Clinical: (> 3 mths..stretch out their feeds)

Growth failure, poor feeding, episodes of ketotic hypoglycemia -fits, lethargy

Exam:

Course facies, cherubic, lethargic, hepatomegaly

Labs:

a. Basic: CBC - may have low ANC’s
b. metabolic: Ketotic hypoglycemia, raised (lactic acid, uric acids, triglycerides)

Treatment:

A. Acute decompensation management principles1.

  1. ABCs
  2. Prevent catabolism - (downstream hypoglycemia is more impt than upstream toxicity)
    a. iv dextrose
    b. Treat inciting factor
    c. Monitor for acute complications/sequelae

B. Long term complications

Neutropenia and frequent infections

malignant transformation of Hepatic adenomas

Hypertension, and renal insufficiency.

IBD

Long term treatment

  1. Frequent doses of cornstarch or continuous NGT
  2. Education of parents for Sick day monitoring
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40
Q

Features of Mc ardles?

Defect, clinical signs, blood and genetic tests and management?

A

Defect in the enzyme myophosphorylase.

Clinical -(Onset -adolescence)

  1. exercise induced muscle pain (followed by a “second wind” phenomenon in which the patient briefly feels better.)

, exercise induced fatigue, and rhabdomyolysis. Myoglobinuria

  1. renal injury can occur.

Blood:

  1. Raised CK concentrations following exercise.
  2. muscle biopsy, which demonstrates deficient enzyme and glycogen within the myocytes.
  3. DNA analysis of the PYGM gene- (no need biopsy).

Management:

  1. Avoidance of strenuous aerobic and isometric exercise
  2. light aerobic activity as tolerated.
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41
Q

Lysosomal disorder case?

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42
Q

What are the common Lysosomal disorders?

A
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43
Q

What are the features of Fabry’s disease?

A
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44
Q

Refrences for Lysosomal storage disorders

A
  1. Lysosomal storage diseases USMLE dirty https://www.youtube.com/watch?v=7udUG8KkN_E
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45
Q

What are more features of Fabry’s diseass?

Clinical males & female, Diagnosis and treatment?

A

Genetics: X Linked recessive

Males: late childhood/early adolescence

Female heterozygotes in adolescence/adulthood.

1. Skin: acroparesthesias (painful hands and feet) , reduced sweating, angiokeratomas

2. Gastro: recurrent abdominal pain.

  1. Renal: proteinuria + renal failure..dialysis & transplant.( if untreated)

(Females-renal failure 10 years)later than males,

  1. early arthrosclerosis and stroke, and cardiac hypertrophy.

Diagnosis:

  1. low agalactosidase enzyme activity in males.
  2. DNA testing esp in females (near-normal

enzyme activity.

Treatment: ERT is available for treatment.

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46
Q

What are the features of Gauchers disease?

A

Pathogenesis: accumulation of glucocerebroside in the liver, spleen, and bone marrow. More common in individuals of

Ashkenazi Jewish decent.

Clinical: M

  1. Marrow obliteration and splenic sequestration/hepatosplenomegaly
    - anemia, thrombocytopenia & bone paindue to , , and . The

brain is not affected, although Parkinsonism has been

recently shown to be associated with Gaucher disease.

2. Neuropathic variants (types 2 and 3)

Type 2 is- rapid, and severe neurodegeneration in childhood

Type 3 ocular + neuromotor dysfunction severe visceral signs

Treatment: ERT and substrate inhibitors are available for treatment.

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47
Q

What are the features of Tay Sachs?

A
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48
Q

What are the features of Nieman Pick disease?

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49
Q

What is the differnce and similarity between Niemann Pick and Tay Sachs ?

A
  1. Niemann Pick has hepatomegaly and Tay Sachs does not
  2. Both have cherry red spots on macula
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50
Q

What are the features of Krabbe’s disease?

A

Has Globoid cells, like the Krabbe is out of this world

Enzyme: galactosylceramidase.

Buildup:

Clinical: (infantile neurodegeneration). Infants present in the 1. 1. Neuro: increasing muscle tone, irritability, fits, vision loss, and developmental regression,2. Recurrent fevers without source can been seen.The infant develops with

Diagnosis:

  1. is by enzyme assay or DNA analysis.
  2. CSF protein elevated

Progx/Management:

  1. Death
  2. HSCT with mixed results.
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51
Q

What are the features of Hunters disease?

A
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52
Q

What are the features of

  1. MPS 1 (Hurler syndrome )

MPS 2 (Hunter syndrome)

A

1. MPS 1 (Hurler syndrome ) - progressive

  • Enzyme: L-Iduronate*
  • Buildup: Dermatan Sulphate*
    a. Corneal clouding, coarse facial features, hepatosplenomegaly, bony deformity, and developmental regression.

Progx:

1. Without treatment - fatal.

  1. ERTand HSCT effective
  2. MPS II (Hunter syndrome) - X marks the sport (Xlinked and no cataract)…rifle against the skin/”derm”
    * Enzyme: Iduronate Sulphatase*
    * Buildup: Dermatan Sulphate*

Clinical: similar to MPS I but no corneal clouding. MPS I and II

Both Hurler and Hurlers have milder forms without developmental regression that are amenable to ERT, which does not cross the blood-brain barrier.

53
Q

What are the HIGH YIELD takeaways with metabolic diseases?

A
54
Q

What are more features of Tay Sachs?

Pathophysiology, Clincial, Diagnosis, Prognosis and management?

A

Pathophysio:

1.deficiency in the enzyme b-hexosaminidase A.

accumulation- sphingolipid GM2 ganglioside

  1. more common in Ashkenazi Jews

Diagnosis:

a. DNA analysis -HEXA gene
b. enzyme assay of b-hexosaminidase A in leukocytes.

Clinical: (early infancy)

  1. Neuro: with weakness, startle reflex ++, Myoclonic jerks and developmental regression , macrocephaly+, seizures, spasticity, unresponsiveness+
  2. Eye: cherry red spots on the maculae, vision loss, Visceromegaly

Progx/Management:

1. no effective treatment , fatal by age 4 years.

  1. Carrier screening reduced the incidence in Ashkenazi Jews.
55
Q

MPS 3-5

A

1. MPS III (Sanfilippo syndrome) (neurodegenerative condition)

a. slow developmental regression, with death < 20 yr
b. visceral and bony manifestations - less prominent
c. behavioral, attention issues before motor and cognitive regression.
2. MPS IV differs by..
- severe bony involvement and short stature.
3. MPS VI is very similar to MPS I (Hurlers) but never has developmental regression.

56
Q

What are PEROXISOMAL DISORDERS?

A

The peroxisome is a cellular organelle with disparate functions,

including oxidation of very long-chain fatty acids (VLCFAs).

57
Q

What is Zellweger syndrome?

A

Cause: near or complete absence of peroxisomes.

Clinical:

  1. Neuro: dysmorphic facial characteristics, seizures,

hypotonia ++, and hearing and vision deficits.

  1. liver disease, characteristic bone involvement,

Diagnosis:

  1. screening by plasma VLCFA analysis

2. Radiology: MRI brain brain - leukodystrophy -Abn myelination

Progx: fatal in infancy.

58
Q

What is Adrenoleukodystrophy?

A

Cause: X-linked condition from deficiency in peroxisomal oxidation of VLCFAs.

  • *Clinical**: (school-age boys)
    1. developmental regression, new-onset spasticity
  1. adrenal failure (acumulation in adrenal glands)

Diagnosis:

  1. screening by plasma VLCFA analysis

2. MRI: white matter disease,

Management: HSCT may halt progression

59
Q

How do mitochondrial disorders present?

A

Cause:

  1. multisystemic conditions from mutations in the mitochondrial genome or nuclear genes required for mitochondrial function
  2. Genetics:
    a. Point mutations in the mitochondrial genome are

transmitted via maternal inheritance,

b. deletions or duplications in the mitochondrial genome are usually sporadic

c. mutations in nuclear genes required for mitochondrial function are inherited in a mendelian pattern, usually

autosomal recessive.

  1. most important functions is the production

of cellular energy in the form of ATP via

the respiratory chain - affect brain, skeletal and cardiac muscles, and the eye.

Diagnosis:

  1. Muscle biopsymay show ragged red fibers on lightmicroscopy.
  2. next-generation DNA sequencing of multigene

panels for nuclear gene mutations, sequencing of the mitochondrial

genome, and specific assays of muscle respiratory

chain activity.

60
Q

What are 3 specific mitochondrial disorders

A

1. MELAS (mitochondrial encephalomyopathy, lactic acid,

and strokelike episodes)

Cause: maternally inherited mutation

in the mitochondrial tRNA for leucine.

Clinical: (adolescence)

1. Neuro: recurrent strokelike episodes (hemiparesis or other focal neurologic signs (posteriortemporal, parietal, and occipital lobes)

  1. At least 2 of the following: seizures (focal or generalized), dementia, recurrent migraine headaches, and vomiting….and headaches
  2. Lactic acidosis, ragged red fibers (RRF), orboth

4. Other: diabetes mellitus

a. Muscle: exercise intolerance, myopathy, ophthalmoplegia, b. b. eyes: pigmentary retinopathy,
c. Cardiac: hypertrophic or dilated cardiomyopathy, cardiac conduction defects,
d. Sensory: deafness, cortical blindness,
f. endocrinopathy(diabetes mellitus), and proximal renal tubular dysfunction,
g. development: delayed motor and cognitive development, short stature.

2. Kearns-Sayre syndrome (

Cause: sporadic, noninherited partial deletions of the mitochondrial genome

Clinical:

Neuro: progressive external ophthalmoplegia

  • *Cardiac:** conduction abnormalities, cardiomyopathy
  • *Metabolic**: Common features include , lactic acidosis, and .
  1. Leigh syndrome (Respiratory chain disorders)

Genetics: autosomal recessive pattern and

are related to mutations in nuclear genes important for

assembly, maintenance, or production of the respiratory

chain (but may also be maternally inherited due to mitochondrial point mutations).

Clinical: (infancy)

Neuro: hypotonia, muscle weakness, global

developmental delays, and seizures.

Metabolic: lactic acidosis,

Diagnosis: Neuroimaging

may show basal ganglia lesions consistent with Leigh syndrome

61
Q

What do the mucopolysacharisoses look like?

A
62
Q

What are lyzozymal disorders, what causes them and which are the common ones?

A

Hereditary, progressive diseases caused by mutations of genes coding for lysosomal enzymes needed to degrade glycosaminoglycans- GAG’s (acid mucopolysaccharides).

The most common subtype is MPS-III, followed by MPS-I and MPS-II.

63
Q

What are essentials between Hunters, Hurlers and Sanfilippo syndromes?

Genetics, Enzyme and build chemicals?

A
64
Q

What are the main Rx goals in MPS diseases?

A

Primary prevention through genetic counseling and

Tertiary prevention to avoid or treat complications:

Respiratory, cardiovascular, hearing loss, carpal

tunnel syndrome, spinal cord compression, hydrocephalus

65
Q

Which MPS types benefits from enzyme replacement?

A

Approved for MPS I, MPS II, and MPS VI.

66
Q

What are the benefits of enzyme replacement therapy in MPS?

A

Reduces organomegally, improves growth, joint mobility, and physical

endurance.

  • reduces sleep apnea and urinary GAG excretion.
  • do not cross BBB, so only for mild CNS problems involvement.
  • start enzymes before BMT for extra CNS problems

How do you manage enzyme and BMT Rx?

  • Enzyme and BMT Rx useful in Hunter disease, MPS VI
67
Q

What are the benefits of enzyme replacement therapy in MPS?

A

Reduces organomegally, improves growth, joint mobility, and physical endurance.

  • reduces sleep apnea and urinary GAG excretion.
  • do not cross BBB, so only for mild CNS problems involvement.
  • start enzymes before BMT for extra CNS problems

How do you manage enzyme and BMT Rx?

  • Enzyme and BMT Rx useful in Hunter disease, MPS VI
68
Q

Which MPS types benefits from enzyme replacement?

A

Works for MPS I, II, and VI (Maroteaux-Lamy disease (MPS VI)

69
Q

What are the benefits and risks of BMT Rx in MPS?

A

General:

  • increased life expectancy, growth better,
  • joint stiffness, facial appearance, hepatosplenomegaly
  • Enzyme activity in serum and urinary GAG excretion normalize.

Resp/heart:heart disease, upper airway obstruction, OSA

Neuro:

  • Prevents CNS degeneration but does NOT correct it
  • improves communicating hydrocephalus, and hearing loss.
  • target young kids, severe MPS I, anticipated CNS probs, BMT < 2 yr,

baseline IQ >70.

Not correct: skeletal and eye problems

Risks:death or 1’ graft failure ≈30% of the patients.

70
Q

What are the essentials of the 3 important MPS syndromes?

A
71
Q

What are the clinical features of MPS 1-3?

A
72
Q

What do I need to know for the RCPSC exam in metabolics?

A
73
Q

WHAT ARE THE TYPES OF SMALL AND LARGE MOLECULE IEM’S?

A
74
Q

What are the pathways for cause of aminoacidemias?

A
75
Q
A
76
Q

What is the pathway problem in UCD?

A
77
Q
A
78
Q

What is the presentation of UCD’s?

A
79
Q

What are the initial tests you request for with high NH3?

A

Basic:

a. CBC - prolonged metabolic stress may lead to pancytopenia

b. Septic work up - b cultures, urine, LP and CXR

Elect:

  • low urea if UCD raised if organic acidemia)
  • N anion gap if UCD (raised if organic acidemia)

maybe hypoglycemia

Blood gas:

If UCD initial alkalosis…later +/- acidosis

Iforganic acidemia acidosis

LFT’s:

NH3 raised in UCD and organic acidemia

Raised transaminases and bilirubin if liver failure

80
Q

What are the What are the diagnostic tests you request for with high NH3?

A

Blood:

a. aminoacids + organic acids + carnitine and acyl carnitine
b. genetics testing - mutation analysis important for future pregancies and siblings

Urine: organic acids + orotic acid

81
Q

Where does N Acetyl synthetase glutamase fit into the UCD?

A
82
Q

Extra bits in mangement of acute UCD crises? v 1

A
83
Q

Extra bits in mangement of acute UCD crises? v 2

A
84
Q

Extra bits in mangement of acute UCD crises? v 3

A
85
Q

What are the most important UCD’s for the exam?

A
86
Q

How is organic acid metabolism related to the urea cycle and why is NAGS comptetively inibited by organic acidemias?

A

This is why organic acidemias result in high NH3 levels

87
Q

How do organic acidemias present?

A
88
Q
A
89
Q

After essentail labs, what diagnostic tests do you order for organic acidemias?

A
90
Q

What are the management principles for organic acidemias?

A
91
Q

How do you Stop protein/aa source and stop catabolism in OAA’s?

A
92
Q

How do you Eliminate toxic metabolites in OAA’s?

A
93
Q

How do you prevent and monitor for sequelae in OAA’s?

A
94
Q

What is the chronic/Long term management of OAA’s?

A
95
Q

Which specific OAA’s do you need to remember for the exam?

A
96
Q
A
97
Q

Why is the clinical presentation of Aminoacidopathies so heterogeneous?

A
98
Q

What causes the clincial problems with Aminoacidopathies?

A
99
Q

For PKU what do you know about the following?

—Basic science:

Clinical presentation—

—Diagnosis—

Treatment

A
100
Q

For Homocysteinuria, what do you know about the following?

—Basic science:

Clinical presentation—

—Diagnosis—

Treatment

A
101
Q

For MSUD what do you know about the following?

—Basic science:

Clinical presentation—

—Diagnosis—

Treatment

A
102
Q

For Tyrosinemia what do you know about the following?

—Basic science:

Clinical presentation—

—Diagnosis—

Treatment

A
103
Q

In glucose metabolism- what the pathways that regulate high and low glucose?

A
104
Q

How do glucose and glycogen link into the Krebs cycle?

A
105
Q

What are the 3 carbohydrate metabolism disorders to learn for the exam,?

A
106
Q

What is the metabolic cause for Pompe’s sidease (GSD 2?

A
107
Q

What is the clinical presentation of Pompe’s diseases?

A

Heart- Short PR interval and high QRS waves

108
Q

What si the management for Pompe’s disase?

A
109
Q

Ho wis galactose metabolism linked to glucose and Krebs cycle?

A
110
Q

What causes Hereditary Fructose Intolerance?

A
111
Q

How does Hereditary Fructose Intolerance present and ho wdo you manage it?

A
112
Q

What is the normal metabolism pathway for lipids?

A
  1. Triglycerides are broken up by lipolysis to the Glycerol back bone and free fatty acids (short, medium and long chain)
  2. Carnitine is essential for metabolism of fatty acids-long chain
  3. B oxidation is needed to break the fatty acids into acetyl CoA and to feed the Krebs cycle
113
Q
A
114
Q

What is the abnormal metabolism pathway for lipids?

A
115
Q

How do complex Molecule/Organelle Disorders generally present? - peroxisomal and lysosomal disorders..

A
116
Q

Which are the Sphingolipidoses?

A
117
Q

What is the work up for mitichondrial diseases?

A
118
Q

What are the differentials for high NH3 presentations?

A
119
Q

What is the approach to high NH3 by using info from acidosis, ketones and liver function?

A
120
Q

What are the metabolic differrentials for Hypoglycemia?

A
121
Q

What labs do you order with a hypglycemic child?

A
122
Q

Ho wdo you interpret the critical sample of low blood sugar?

A
123
Q

What are the differentials for metabolic and non metabolic causes of Conjugated Hyperbilirubinemia?

A
124
Q

What are the causes for Neonatal Seizures?

A
125
Q

What are the DDx for a Floppy infant?

A
126
Q

Ho wdo you apprroach investigation lyzozymal disorders?

A
127
Q

How do you describe GM1 Gangliosidoses?

A

1. Early infantile type: AR trait

Cause: deficient activity of β-galactosidase, a lysosomal enzyme encoded by a gene on

Accumulation of: GM1 gangliosides in the lysosomes

CNS and visceral/liver cells,

Clinical:

Neuro: Developmental delay then GTC seizures, 50% of macular cherry red spot

Liver/skin; hepatosplenomegaly, edema, angiokeratoma

Skeletal:

anterior beaking of the vertebrae,

enlargement of the sella turcica

thickening of the calvarium, are present.

Face: low-set ears, frontal bossing, a depressed nasal bridge, and long philtrum. Up to

Progx:

> 1 yr most -blind and deaf, CNS impairment++

Death by 3-4 yr of age.

  1. Onset of late infantile GM1 -1 and 3 years.(Type II GM1 gangliosidosis )

Neurological symptoms include ataxia, seizures, dementia, and difficulties with speech.

3. The juvenile-onset form of GM1 gangliosidosis (Type II GM1 gangliosidosis )

Neuro: ataxia, dysarthria, Low IQ, and spasticity. Deterioration may survive through the 4th decade of life.

No hepatomegaly, facial abnormalities, norskeletal features seen in type 1 disease.

  1. Onset of adult GM1 is between ages 3 and 30.

muscle atrophy, CNS problems - severe and progress at a slower rate than in other forms of the disorder,

corneal clouding in some patients, and dystonia (sustained muscle contractions that cause twisting and repetitive movements or abnormal postures).

Angiokeratomas lower part of the trunk of the body.

Most patients have a normal size liver and spleen.

Prenatal diagnosis is possible by measurement of Acid Beta Galactosidase in cultured amniotic cells.

128
Q

What are the types of Sphingolipidoses?

A

Royal College Peds 2021 (55 decks)

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