Week 1: Inborn Errors of Metabolism (IEMs) Flashcards
Based on the metabolic pathway below; What is the most likely enzyme deficiency in a 3-day-old male
elevated serum ammonia, citrulline, glutamine, and abnormal plasma amino acids
low arginine and ASA (argininosuccinic acid)
acid is measured in the blood and the actual metabolites end in -ate
Argininosuccinic acid (ASA) synthetase deficiency
Why is the serum ammonia level elevated in the infant with argininosuccinic acid synthetase deficiency?
The urea cycle isn’t working, preventing detoxification of ammonia produced by amino acid catabolism.
Why are glutamine levels elevated in an infant with argininosuccinic acid synthetase deficiency or with many other urea cycle disorders (UCD)?
Ammonia is attached to alpha-ketoglutarate to form glutamate and then glutamine as a secondary detoxification method with urea capture and release
What do patients with a Urea Cycle disorder (UCD) or any condition with a buildup of ammonia have neurological symptoms?
ammonia is a neurotoxin
What enzyme deficiency is indicated by massive elevations of leucine, isoleucine, and valine. In addition, the 5-day-old boy urine organic acids reveals elevated 2-keto-3-methyvaleric acid, 2-ketoisocaproic acid, 2-ketoisovaleric acid, 2-OH-isovaleric acid, 2-OH-3-methylvaleric acid, 2-OH-isocaproic acid.
Branched chain ketoacid dehydrogenase deficiency (maple syrup urine disease)
What vitamin does Branched Chain Ketoacid Dehydrogenase (BCKAD) deficiency require
B1
Why is the ammonia level normal in a 5-day-old boy with branched chain ketoacid dehydrogenase deficiency?
This patient’s urea cycle is functioning normally.
What enzyme deficiency is most likely in an 8-month-old girl Plasma acyl carnitine analysis revealed low free carnitine and elevated levels of C12, C14, C14.1, C16, and C18 acyl-carnitines?
Very long-chain acyl-CoA dehydrogenase deficiency (VLCAD)
Other possible deficiencies include CPT2 or translocase (CACT) deficiency.
What length is considered a short-chain, medium-chain, long-chain, and very-long chain fatty acid?
Very Long-chain fatty acid is >16, but sometimes grouped with long-chain.
Why does someone with a fatty acid oxidation metabolic error have low blood glucose?
Inability to oxidize fatty acids increases reliance on glucose and hampers gluconeogenesis due to lack of ATP.
Why does someone with a fatty acid oxidation metabolic error have low or absent ketones?
Ineffective fatty acid oxidation prevents ketone production in the liver from acetyl CoA.
What lab test should be ordered for an infant with hypoketonic hypoglycemia?
Plasma acyl-carnitines
Insulin and C-peptide levels can also be tested for hyperinsulinemia.
What enzyme deficiency is suspected in a 1-day-old girl with elevated methylmalonic acid as well as elevated 3-OH-propionic acid, lactic acid and severe metabolic acidosis?
Methylmalonyl CoA mutase deficiency
From which vitamin is the cofactor for methylmalonyl CoA mutase derived?
Vitamin B12
In addition to the gene encoding the enzyme methylmalonyl CoA mutase, this disorder can also be caused by the inability to convert a vitamin into the enzyme cofactor. Why might it be important to determine which gene causes this disorder?
A deficiency in one of the enzymes required to convert B12 into the cofactor can be quite easily treated by providing the upstream metabolite so the cofactor can be synthesized
What enzyme deficiency is indicated in a 2½-year-old boy with a distended abdomen (hepatomegaly on US) and lab values of
Blood glucose: 39 mg/dL (after an overnight fast)
Elevated serum AST, ALT and CK
Ketones in urine
Liver shows accumulation of a dextrin like substance
Glycogen debranching enzyme deficiency
