Just to add to what some others have said, this is in First Aid as well. FA 2020 page 85:
Organic acidemias most commonly present in infancy with poor feeding, vomiting, hypotonia, a high anion gap metabolic acidosis, hepatomegaly, and seizures.
The organic acid accumulation does 2 things:
Organic acids inhibit gluconeogenesis, leading to fasting hypoglycemia which then causes ketoacidosis, causing a high AG metabolic acidosis
Organic acids inhibit the urea cycle, leading to hyperammonemia
Can’t help much on the exact reasoning why, but there are a few UWorld questions on this where if a neonate has hypoglycemia, ketosis and hyperammonemia, a organic acid disorder should be suspected (propionic acid or methylmalonic acid). Less suspicious of an RTA cause hypoglycemia is not characteristic of that.
My reasoning on this questions was simpler - I think they wanted us to pick an autosomal recessive disease based on pattern of kids affected (both females are affected - can't be anything X-linked); boy was healthy - rule out mitochondrial. With rest - rule out because of increased ammonia and infantile presentation. Only organic acid metabolism disorder left
Ornithine transcarbamylase deficiency. Most common urea cycle disorder. X-linked recessive (vs other urea cycle enzyme deficiencies, which are autosomal recessive).
Interferes with the body’s ability to eliminate ammonia.
Often evident in the first few days of life, but may present later. Excess carbamoyl phosphate is converted to orotic acid (part of the pyrimidine synthesis pathway).
Findings: Increased orotic acid in blood and urine, Decreased BUN, symptoms of hyperammonemia. No megaloblastic anemia (vs orotic aciduria).
submitted by ∗lsmarshall(465)
Urea Cycle Disorders > Isolated severe hyperammonemia (> 1000; i.e., no other severe metabolic disturbances
Ornithine transcarbamylase deficiency > (most common urea cycle dis.) orotic acidemia/aciduria, hyperammonemia
Organic Acidemias > Hyperammonemia, anion-gap acidosis, ketosis (from hypoglycemia)
Medium-chain acyl-CoA dehydrogenase deficiency > Hyperammonemia, hypoketotic hypoglycemia (seen in β-oxidation disorders, EXCEPT adrenoleukodystrophy)
Liver dysfunction > Hyperammonemia, LFTs messed up, older pt.