clinical features of all organic aciduria
vomitting, enurological decompensation, failure to thrive (don't eat as much because it makes them sick) and unusual odors
laboratory features of organic acidurias
amino aciduria, organic aciduria
How are these diagnosed?
urine organic acid analysis by gas chromatography/mass spectrometry
What are the branched chain amino acids that are affected in Maple syrup urine disease
leucine, isoleucine and valine
what enzyme is affected in MSUD and what does it normally do?
decarboxylation by branched chain alpha ketoacid dehydrogenase (with TPP cofactor)
how is MSUD treated?
with dietary restriction of branched chain amino acids
What builds up in MSUD?
The alpha keto acids after the deamination step of the amino acid is what builds up. But because this reaction is reversible, the build up causes it to go backwards and the corresponding amino acid builds up
what form of heterogeity does MSUD present?
genetic heterogeneity, different mutations on different genes all give you MSUD
which form of MSUD is the most common/severe?
the classical form -- E1 alpha subunit
What compound can be looked for to detect MSUD in amino acid profile?
alloisoleucine which is a different isoform that shouldn't be there
What accumulates in isovaleric acidemia
isovaleryl coA, isovaleric acid, isovaleryl glycine
clinical presentation of isovaleric acidemia
acute -- emesis, acidosis, sweaty feet smell
chronic -- developmental delay
what feeds into the pathway of propinoyl coa to succinyl coa
Odd chain fatty acids
isolated or part of multiple carboxylase deficiency
primary due to methylmalonyl coA mutase deficiency or secondary if cofactor deficiency B12
all 4 carboxylases are deficient
what are the 2 mutants of methlymalonyl coA deficiency
Mut 0 - no activity even with cofactor, CRM - '
Mut - = decreased activity, due to decreased affinity for cofactor, and reduced stability CRM +
what is the cofactor for methylmalonyl coA
what are the 2 enzymes that use cobalamin and what types of cobalamin do they each use
methylmalonyl coA --> adenosylcobalamin
and methlycobalamin ---> methylcobalamin
a problem with adenosylcobalamin causes what?
a problem with methylcaobalamin causes what?
homocysteinuria with low methionine
what does CblA and CblB abormality cause?
abnormalities in Adenosyl Cbl syntehsis only = clinical and biochemical picture identical to mut defects, isolated MMA
CblC and CblD and CblF abnormality cause?
impaired synthesis of both adenosyl and methylcobalamin, so both MMA and homocystinuria
what are secondary findings of methylmalonyl coA mutase deficiency?
hypoglycemia, mild hyperlacticacidemia, hyperammonemia, hyperglycinemia,
what is the primary finding of methylmalonyl coA mutase deficiency
what 4 enzymes is biotin required for?
what enzyme puts biotin on the apoenzyme?
what enzyme recycles biotin from enzymes
what are symptoms of biotinidase deficiency?
neurological (siezures, developmental delay, hypotonia)
dermatological (alopecia, dermatits)
when does the disease present typically?
usually presents later on because the baby is born with the mother's biotin