Enzyme affected: propionyl-CoA carboxylase (a mitochondrial enzyme)
Genes affected: PCCA or PCCB
Chemicals that accumulate: propionyl CoA, propionic acid, 3-hydroxypropionic acid, propionylcarnitine, propionylglycine, 2-methylcitrate
Onset: usually during early childhood due to a metabolic decompensation
Triggers for a metabolic decompensation:
(1) acute trauma
(2) infection or fever
(3) excessive exercise
(4) any physiologic stress
(5) fasting
(6) vomiting
(7) relatively high protein intake
(8) medication
An episode of metabolic decompensation may involve:
(1) vomiting
(2) anorexia
(3) dehydration
(4) lethargy
(5) hypotonia
(6) convulsions
(7) coma
(8) multi-organ failure
Clinical manifestations may include:
(1) hepatomegaly and/or hyperechoic liver
(2) cognitive deficits
(3) anemia, neutropenia, thrombocytopenia and/or pancytopenia
(4) psychomotor retardation
(5) muscular hypotonia and/or movement disorders
(6) CNS lesions (white matter, basal ganglia)
(7) epilepsy
Less common findings may include:
(1) stroke-like episodes
(2) attention-deficit hyperactivity or autism
(3) cardiomyopathy
(4) decreased bone mineral density
(5) constipation
(6) growth retardation and short stature
(7) pancreatitis
(8) optic atrophy
(9) sensorineural hearing loss
Laboratory findings during an acute exacerbation:
(1) metabolic acidosis
(2) lactic acidosis
(3) hyperammonemia
