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24 Cards in this Set
- Front
- Back
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UOA findings in a *well* patient with IVA
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isovalerylglycine (even when well)
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Management for IVA
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No diet (?reduced leu?)
?glycine supplementation? Carnitine supplementation Observe for acidosis when unwell |
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Major presentations of VLCAD (3)
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Infant: with hypertrophic cardiomyopathy
Child: with hypoglycemia Late: with rhabdomyolysis |
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Features of 27 OH-ase deficiency
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Cerebral tendinous xanthomatosis
Cataracts Leg xanthomas Deficient bile acids: Rx Chenodeoxycholate and ADEK PRN Highly increased cholestanol |
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Metachromatic leukodsytrophy
(Testing and Management) |
Need mutations: Pseudodeficiency does occur
ERT available (trial basis) |
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Testing for molybdenum cofactor deficiency
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urine sulfite screen
(for S-sulphocysteine) |
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Increased Leu:Ala ratio
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MSUD (typically ~9)
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Other disorder to be considered if screen positive for MCAD
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GA2
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Enzyme deficiencies in GA2
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GA2 = MADD
(Multiple acylcoA dehydrogenase deficiency) with defects in: SCAD MCAD LCHAD VLCAD |
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Increased alpha-ketoglutarate in 3 week-old on UOA
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Normal
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Increased alpha-ketoglutarate in 3 <i>month</i>-old on UOA
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Needs investigation
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4-OHphenylacetic
4-OHphenylpyruvic 4-OHphenyllactic |
Tyrosinemia or liver disease
Request urine succinylacetone |
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Clinical features of GA1
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Macrocephaly from birth
Micrencephaly, atrophy Very wide sylvian fissures Present with encephalopathic crisis 6-24months (when ill) MRI: T2 increase basal ganglia, restricted diffusion Rigidity, dystonia -> CP Feeding / swallowing -> G-tube |
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Catabolic defects in GA1
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Lysine
OHlysine Tryptophan Enzyme: glutarylcoA dehydrogenase (mitochonrial matrix) glutaryl--->crotonylcoA |
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Accumulating metabolites in GA1
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GA
3-OHglutaric acid glutaconic acid glutarylcarnitine |
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Enzymes affected by molybdenum cofactor deficiency
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oxidases
sulphite oxidase xanthine dehydrogenase aldehyde oxidase |
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What are clinical features of pyridoxine-responsive epilepsy?
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Seizures from before / shortly after birth
Rapid response to pyridoxine Refractory to other anticonvulsants Dependence on a maintenance dose Absence of B6 deficiency |
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Seizure type in B6-responsive epilepsy
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Any
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Gene, enzyme, activity in pyridoxine-responsive epilepsy
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ALDH7A1 (Antiquitin) (Dominant)
alpa-aminoadipic semialdehyde / P6C dehydrogenase |
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Testing for pyridoxine (B6)-responsive seizures
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trial of B6 (IV) under EEG monitoring
urine alpha-aminoadipic semialdehyde |
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Organic acidemias presenting exclusively with: epilepsy/myoclonus, ataxia,
metabolic stroke, macrocephaly (5) |
Cerebral OA disorders:
GA1 D-2-hydroxyglutaric aciduria L-2-hydroxyglutaric aciduria 4-OHbutyric aciduria (GHBuria) N-acetylaspartic aciduria |
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Possible structural basis for CNS symptoms in cerebral OA disorders
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Accumulating compounds are similar to glutamate (excitatory) and/or are neurotransmitters (eg. GHB)
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UOAs in GA1
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<i>May</i> show glutaric acid
Low-excretor group: may be normal |
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Mechanism of neurotransmitter disorder in B6-responsive seizure
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alpha-aminoadipic semialdehyde (AASA) accumulates due to defective catabolism
AASA is in equilibrium with piperidine-6-carboxylate (its cyclic form) P6C condenses with, depletes B6 glutamic acid decarboxylase cannot function without its B6 cofactor Glutamate ---x--> GABA |
