Organic Acid Disorders |
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| Disease Name | Propionic acidemia |
| Alternate name(s) | Propionyl-CoA carboxylase deficiency, PCC deficiency, Ketotic hyperglycinemia |
| Acronym | PA |
| Disease Classification | Organic Acid Disorder |
| Variants | Yes |
| Variant name | Late onset (> 6weeks) |
| Symptom onset | Neonatal |
| 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. |
| Other | N/A |
| 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. |
| Inheritance | Autosomal recessive |
| General population incidence | 1:35,000 to 1:75,000 (may be underestimate as infants may die undiagnosed) |
| Ethnic differences | Yes |
| Population | Saudi Arabia |
| Ethnic incidence | 1:2000 to 1:5000 |
| Enzyme location | Mitochondria |
| Enzyme Function | Intermediary in the metabolism of isoleucine, valine, threonine and methionine. |
| 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 research basis. |
| 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. |
| MS/MS Profile | N/A |
| OMIM Link | www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=232000 |
| Genetests Link | www.genetests.org |
| Support Group | Organic Acidemia Association Save Babies through Screening Foundation |
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