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Exam > Metabolics > Flashcards

Metabolics Flashcards

1
Q

Aminoacidopathies

A

Unable to metabolise amnio acids
Does not cause sig acidosis and hypoglycaemia
Amino acids toxic to organs
Ix: serum/urine/CSF amino acids

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2
Q

PKU

A

Aminoacidopathy- normal bloods
Defect in phenylalanine hydroxylase - cannot break down phenylalanine to tyrosine
Excess phenylalanine causes neurotoxicity
AR
Presents 6-8 months with developmental delay, seizures, vomiting, eczema
“Musty” smell, light colouring
Rx: low phenylalanine diet

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3
Q

MSUD

A

Aminoacidopathy- normal bloods
Inability to break down branch chain amino acids- leucine, isoleucine, valine
(BCAAs make up 20% of dietary protein)
Leucine toxic to brain- presents ~10 days with encephalopathy/coma

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4
Q

Tyrosinaemia I

A

Aminoacidopathy- normal bloods
Enzyme block causes high levels of succetylacetone - toxic to liver
Presents ~ 6 months with liver disease
Treatment blocks the enzyme above the block
Hypoglycaemia

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5
Q

Tyrosinaemia II

A

Aminoacidopathy- normal bloods

Tyrosine toxic to skin and cornea- keratitis and keratosis

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6
Q

Organic acidopathies

A

Organic acid- a carbon-containing compound containing an acidic group- breakdown products of amino acids

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7
Q

Organic acidopathies

  • What are organic acids
  • Ix
  • Clinical features
  • Organs affected
A

Organic acid- a carbon-containing compound containing an acidic group- breakdown products of amino acids
Transaminases remove the amino group from amino acids, making organic acids
Ix: Urine organic acids or acylcarnitine profile
Tend to cause severe acidosis, ketosis, hypoglycaemia, hyperammonaemia, elevated lactate
Particularly affect brain (comatose, hypertonic, seizures), liver (hepatitis)
Mx:
Cease protein intake, commence carnitine (buffers Acyl-CoA metabolites), 10% dextrose or SMOF, ammonia scavengers, renal replacement therapy

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8
Q

Methylmalonic acidaemia

A

Organic acidopathy

Bad outcome

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9
Q

Proprionic acidaemia

A

Organic acidopathy
Bad outcome- proprionic acid very neurotoxic
Metabolic stroke, esp bilateral basal ganglia

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10
Q

Isovaleic acidaemia

A

Organic acidopathy
Sweaty feet smell
Better outcome than other organic acidaemias

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11
Q

Lysosomal storage disease

  • What are lysosomes
  • Clinical features
  • Ix
A

Cell organelle- break down cellular waste production
Initially normal children who over months-years develop symptoms- developmental regression, seizures (no acute crises)
Ix: urinary GAGs (glycosaminoglycans), measure lyosomal enzymes in blood (white cell enzymes)/ liver/muscle/skin biopsy

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12
Q

Mucopolysaccharidoses

A

Lysosomal storage disease
Type 1- Hurler
Type 2- Hunter (X linked- rest are AR)
Type - Sanfilippo
Type 4- Morquio (non-neurological, hyper-extensible)
Coarse facial features, short stature, developmental delay/cognitive impairment
Respond early to BMT

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13
Q

Tay-Saches, Sandhoff

A

Lysosomal storage disease
- Sphingolipidosis
May have very early normal development, but usually severe developmental regression by a few months of age, hypotonic and cherry-red spot on retina but otherwise normal examination
Late onset Tay Sachs- teenager with psychosis

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14
Q

Leukodystrophy

A

Lysosomal storage disease - Sphingolipidosis
Eg. Metachromatic leukodystrophy, Krabbe disease
Impaired motor function (white matter disease) similar to CP, later cognitive decline and dementia
BMT

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15
Q

Gaucher disease

A

Lysosomal storage disease - Sphingolipidosis
Symptoms due to bone marrow and organ infiltration
Splenomegaly, hepatomegaly, bone marrow supression- more chronic presentation than leukaemia, pathological fractures
10x greater risk of Parkinsons disease
Good response to enzyme replacement therapy

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16
Q

Neimann Pick

A

Lysosomal storage disease - Sphingolipidosis
Liver and brain
Variable presentation- isolated hepatomegaly, developmental regression
FBC with histiocytes

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17
Q

Fabry disease

A

Lysosomal storage disease - Sphingolipidosis
MC in total, but more common in adults
Renal failure, cardiomyopathy, pain (esp in children), strokes

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18
Q

Urea cycle disorders

- What does the urea cycle do

A

Urea cycle converts nitrogen waste products (ammonia) in to urea
Ix: very high ammonia, can then measure specific chemicals involved in urea cycle
Rx: restrict protein to minimum needed to grow
Ammonium scavengers0 sodium benzoate, sodium phenylbutyrate, L-arginine, Carbaglu (NAGS)
Provide deficient metabolites eg. arginine, citrullinine
In a crisis- haemofiltration/ haemodialysis

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19
Q

Ornithine transcarbamylase

A

Urea cycle disorder- MC
X linked- severe in boys, mild in girls
Classical- encephalopathy/coma in the first week of life
50% mortality with neonatal presentation, 75% of survivors die in childhood

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20
Q

Fatty acid oxidation disorders

A

Production of ketones (and reducing substances) once glycogen stores run out
Hypoketotic hypoglycaemia, hyperammonaemia, lactic acidosis
Cardiomyopathy
Rhabdomyolysis with significant exercise
Acute hepatomegaly/liver injury
Ix: acylcarnitine profile
Rx: glucose 10% acutely, carnitine supplementation (mops up acyl-coA), avoidance of fasting

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21
Q

MCAD

A

Fatty acid oxidation defect- MC
1/40 carriers in Aus
AR- ACADM gene missense mutation
Hypoketotic hypoglycaemia during periods of fasting
Less unwell after age 3-4 -better glycogen stores
Well otherwise

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22
Q

VLCAD

A

Fatty acid oxidation defect

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23
Q

Carnitine palmitoyl transferase (CPT)

A

Fatty acid oxidation defect

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24
Q

LCHAD

A

Fatty acid oxidation defect

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25
Q

Mitochondrial disorders

A

Respiratory chain- oxidative phosphorylation
Elevated lactate
Any Sx in any organ at any age
Affects high energy organs- brain, heart, muscles, eyes, liver, pancreas, renal tubules
Adult combinations of rhabdomyolysis with minor exercise, IDDM, renal disease, ophthalmoplegia and ptosis, deafness
Ix: lactic acid, organic acids, moelcular mtDNA

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26
Q

Leigh

A

Infant with strokes in the basal ganglia- dsytonia, spasm, variable consciousness level
MRI- T2 hyperintensity in basal ganglia

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27
Q

MELAS

A

Metabolic encephalopathy, lactic acidosis, stokes

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28
Q

Peroxisomal disorder

A

Peroxisome breaks down, and makes things eg. cell membranes

Ix: elevated VLCFA

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29
Q

Adrenoleukodystrophy

A

Peroxisomal disorder
X-linked
Younger child- behaviour eg. ADHD, Addison’s disease, vision changes,
50% Addison’s disease in males = ALD
Ix: VLCFA
MRI: T2 hyperintensity in white matter bilaterally

BMT

30
Q

Zellwegger syndrome

A

Peroxisomal biogenesis disorder
Neonate with poor tone, large anterior fontanelle, tall forehead with bitemporal narrowing, poor feeding, dysmorphic
Abnormal brain MRI
Screen with VLCFAs

31
Q

Refsums disease

A

Peroxisomal disorder
Progressive disorder- rash, abnormal movements, retinitis pigmentosa, anosmia
Elevated phytanic acid

32
Q

Glycogen storage disorders

A

Hepatomegaly (develops), hypoglycaemia with ketosis after a shorter period of fasting
FTT, short stature, hepatitis, liver adenoma/HCC, cherubic face, renal disease
Type 1-9- all AR except 9 (XL)
Lower the number, the more severe, the more intensive feeding required
Elevated lactate, elevated ketones

33
Q

Pompe disease

A

Glycogen storage disease II
Neonate with hypotonia and cardiomyopathy- significant cardiomyopathy
Weakness, areflexia

34
Q

McArdle

A

Glycogen storage disease V

Muscle phenotype- sore muscles with minor exertion

35
Q

Metabolic differentials for an unwell neonate (5)

A 
Organic aciopathies- MMA, PA
Aminoaciopathies- MSUD
Urea cycle disorders
Galactoasaemia
Mitochondrial
36
Q

Metabolic differentials for hypoglycaemia in an older child (not a neonate) (3)

A

Fatty acid oxidation disorder
Glycogen storage disorder
Mitochondrial

37
Q

Metabolic differentials for developmental regression

A 
Lysosomal storage disease
Mitochondrial
Peroxisomal- ALD
Urea cycle disorders (not OTC)
MSUD (mild), PKU
Organic acidamia
Other genetic- CDG, Retts, Alexander, VWM
38
Q

Galactosaemia

A

Calactose-1-phosphate uridyl transferase deficiency- inability to break down galactose
GALT gene
Unwell neonate- day 7-8
Jaundice, hepatomegaly, vomiting, hypoglycaemia, seizures, FTT
E. coli sepsis
Classic galactosaemia assoc with hypergonadrotrophic hypogonadism and learning difficulties

39
Q

Metabolic differentials hepatomegaly/hepatitis

A 
Tyrosinaemia
Galactosaemia
GCS
Lysosomal storage disease
Neimann-Pick C
Mitochondrial
40
Q

Metabolic differentials seizures/microcephaly in a neonate

A 
Non ketotic hyperglycinaemia- Maori
Pyridoxine responsive seizures
GLUT-1 transporter
Creatine synthesis/transporter
Sulfite oxidase
Menkes
Folate disorders
41
Q

Main disorders detected on NNST

A 
CF- IRT
Congenital hypothyroidism - TSH
MCAD- octanoyl carnitine
PKU- phenylalanine levels
Galactosaemia- galactose levels
42
Q

Reasons for false negative on NNST- CF

A

NNST only detects ~50% of cases

IRT only elevated in 95% infants with CF
Only top 10% IRTs of each batch sent for genetic testing
Uncommon mutations missed
No pancreatic involvement
Mec ileus
43
Q

Reasons for false NNST tests- hypothyroidism

A 
Patients with a small amount of functioning thyroid tissue which later fails
Pituitary disease (will not have high TSH)
Monozygotic twins- transfusion of euthyroid blood
TSH transiently elevated in LBW and prem neonates, or falsely low due to immaturity of HPT axis
TSH surge first 24-48 hours of life- if test is done too early
44
Q

False negative for PKU on NNST

A

If testing done <48 hours (not enough exposure to phenylalanine in diet)

45
Q

False result for galactosaemia on NNST

A

<24 hours milk feeds- false neg

Immediately post feed- false pos

46
Q

Babies who need repeat NNST

A

LBW <1500g and prem
- Repeat after 2/52 if >1000g, after 4/52 if <1000g
Sick infants not on enteral feeds- repeat after 24 hours on enteral feeds
Same sex twins- repeat 2/52 after birth
Transfusion- collect just prior to transfusion, and again after 2/52

47
Q

Counter-regulatory hormones used in glycogenolysis

A

Adrenaline, glucagon (insulin suppresses)

48
Q

Counter-reguatory hormones used in proteolysis

A

Cortisol (insulin suppresses)

49
Q

Counter-regulatory hormones used in lipolysis

A

GH, cortisol, adrenaline (insulin suppresses)

50
Q

Lipolysis

A

Triglyerides = glycerol + fatty acids
Glycerol –> gluconeongeneis
Fatty acids –> fatty acid oxidation

51
Q

Hyperinsulinism

A

= >10mg/kg/min glucose requirement

Hypoglycaemia should be assoc with decreased insulin, increased glucagon/cortisol/GH/adrenaline

Hyperinsulinism suppresses all counter-regulatory hormones, therefore suppresses mechanisms of fuel generation = low glucose, low fatty acids, low ketones

Any detectable insulin in the presence of BGL<2.6 is abnormal

52
Q

Congenital disorders of glycosylation

  • Genetics
  • Ix
  • Clinical features
A

AR
Ix: Transferrin isoforms
Wide variety of symptoms: Hyperinsulinism, coagulation disorder, hypotonia, big ears, abnormal fat pads

53
Q

Glutamate dehydrogenase hyperinsulinaemia

A

2nd MC HI
Children become hypoglycaemic after eating protein (leucine)
Hyperinsulinism and hyperammonaemia

54
Q

Glycogen storage disease type 1

A

AKA glucose-6-phosphatase deficiency
High lactate and hypoglycaemia (late block in glycogenolysis- shunts to lactate)
Most severe GSD- may need cont PEG feeds
Type 1b- assoc with neutropenia, impaired wound healing
Present in the first weeks of life

55
Q

Dumping syndrome

A

In children with GI pathology eg short gut syndrome, rapid uptake of nutrient from the GI triggers a rebound hyperinsulinism

56
Q

How does ammonia caise encephalopathy

A

Ammonia binds glutamate in the brain to form glutamine- has an osmotic effect causing cerebral oedema
Also direct effects on neurotransmitters

57
Q

DDx rhabdo

A

FAOD (not MCAD)
GSD- McArdle, Pompe
Mitochondrial

58
Q

LIPN1 deficiency

A

Intercurrent febrile illness - cell membranes become ‘leaky’
CK >100 000
K very high
33% die due to cardiac arrhythmia

59
Q

Malignant hyperthermia

A

AD
RYR1 gene mutation in >50%
Provoked by volatile anaesthetics + depolarising muscle relaxants = muscle contractions, tachycardia, metabolic acidosis, hyperthermia
Central core myopathy is allelic with MH

60
Q

Lactate:pyruvate ratio- normal

A

Glycogen storage disorders
Disorders of gluconeogenesis
Pyruvate dehydrogenase deficiency

61
Q

Lactate:pyruvate: high

A

Mitochondrial disorders

Shock/sepsis

62
Q

Energy utilisation for hours fasting, and disorders assoc with hypoglycaemia during this time

  • 0-2 hrs
  • 2-6 hrs
  • 6-12 hrs
  • 12-24 hrs
A

0-2: glucose = hyperinsulinism
2-6: Glycogen = GSD
6-12: Gluconeogenesis = GSD 0, disorders of gluconeogenesis
12-24: b-oxidation of fatty acids = FOAD, GH/cortisol deficiency

63
Q

How to calculate glucose requirement (in mg/kg/min)

A

% glucose x mL/kg/day / 144

64
Q

Where is glycogen stored

A

Liver (main source of that is used to maintain BGL) and kidney (minor stores for BGL)
Muscles- most glycogen stored here, but only used to supply muscles with glucose

65
Q

Fructose-1,6-bisphosphatase deficiency

A

Disorder of gluconeongenesis
Hypoglycaemia, hepatomegaly +/- liver disease, ketoacidosis, FTT
Triggered by fructose

66
Q

Hereditary fructose intolerance

A

Disorder of gluconeogenesis
Aldose B deficiency
Hypoglycaemia, hepatomegaly +/- liver disease, ketoacidosis, FTT
Triggered by fructose

67
Q

What does carnitine do

A

Cotransporter- helps LCFA and VLCFA in to mitochondria for b-oxidation
(MCFA can pass through without help)

68
Q

Reye syndrome

A

Rapidly progressive encephalopathy + liver toxicity
Often shortly after viral infection eg. influenza, varicella
90% cases assoc with aspirin use
Can also be due to IEM
Hypoglycaemia, hyperammonaemia

69
Q

Glycolysis

A

Process of converting glucose to pyruvate

70
Q

Menkes

A

X linked
Serum copper and ceruloplasma
Seizures, developmental delay, hypotonia
Kinky hair

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