Organic Acid Disorders
|Disease Name||Propionic acidemia|
|Alternate name(s)||Propionyl-CoA carboxylase deficiency, PCC deficiency, Ketotic hyperglycinemia|
|Disease Classification||Organic Acid Disorder|
|Variant name||Late onset (> 6weeks)|
|Symptoms||Episodic crises leading to neurologic damage, coma and death.|
|Natural history without treatment||Metabolic crises may lead to neurologic damage including mental retardation, movement disorders, seizures. coma and sudden death are also possible.|
|Natural history with treatment|| If treatment instituted before metabolic crisis, normal
IQ and development may be seen. Treatment may improve some
symptoms of affected individuals.
|Treatment|| Protein restricted diet with supplementary medical formula,
carnitine supplementation, ketone monitoring, avoidance of
fasting, cornstarch supplementation, biotin supplementation.
Antibiotic (metronidazole and neomycin) treatment. Human
growth hormone therapy.
|Physical phenotype||Characteristic facies including frontal bossing, widened
depressed nasal bridge, epicanthal folds, long philtrum, upturned curvature of the lips and possible hypoplastic/inverted nipples.
|General population incidence||1:35,000 to 1:75,000 (may be underestimate as infants may die undiagnosed)|
|Ethnic incidence||1:2000 to 1:5000|
|Enzyme Function|| Intermediary in the metabolism of isoleucine, valine, threonine
|Missing Enzyme||Propionyl-CoA carboxylyase|
|Metabolite changes||Increased glycine in blood and urine, 3-hydroxypropionic acid in
blood and urine, methylcitrate, tiglic acid, tiglyglycine butanone
and propionyl glycine in urine.
|Gene||Enzyme is made up of alpha and beta subunits coded for by
different genes - PCCA and PCCB.
|Gene location||PCCA = 13q32
PCCB = 3q13.3-22
|DNA testing available||Not available on a routine basis, but may be available on a
|DNA testing detail||No common mutations known.|
|Prenatal testing|| Enzyme activity in amniocytes. GCMS assay in amniotic fluid. If
DNA mutations known, DNA testing is possible.
Organic Acidemia Association