Organic Acid Disorders |
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| Disease Name | Beta-ketothiolase deficiency |
| Alternate name(s) | Alpha-methylacetoacetic aciduria, 2-methyl-3-hydroxybutyric academi, Mitochondrial acetoacetyl-CoA thiolase deficiency, MAT deficiency, T2 deficiency, 3-oxothiolase deficiency, 3-ketothiolase deficiency, 3-KTD deficiency |
| Acronym | BKD |
| Disease Classification | Organic Acid Disorder |
| Variants | No, but there is considerable clinical heterogeneity |
| Variant name | N/A |
| Symptom onset | Late infancy or childhood. Mean age at presentation is 15 months (range 3 days to 48 months). There are documented cases of asymptomatic patients with enzyme deficiency. Frequency of decompensation attacks falls with age and is uncommon after the age of 10. |
| Symptoms | Symptoms include intermittent episodes of severe metabolic acidosis and ketosis accompanied by vomiting (often hematemesis), diarrhea and coma that may progress to death. There is great clinical heterogeneity between patients. Infancy is the period of highest risk for decompensation. Death or neurologic complications can occur. Neurologic damage includes striatal necrosis of the basal ganglia, dystonia and/or mental retardation. Other symptoms include cardiomyopathy, prolonged QT interval, neutropenia, thrombocytopenia, poor weight gain, renal failure and short stature. If neurologically intact, patients are normal between episodes. |
| Natural history without treatment | Clinical outcome varies widely with a few patients suffering severe psychomotor retardation or death as a result of their initial attack and others with normal development and no episodes of acidosis. |
| Natural history with treatment | Despite severe recurrent attacks, appropriate supportive care can result in normal development. |
| Treatment | Avoidance of fasting. Bicarbonate therapy and intravenous glucose in acute crises. Possible protein restriction. Consider carnitine supplementation. |
| Other | N/A |
| Physical phenotype | No dysmorphisms |
| Inheritance | Autosomal recessive |
| General population incidence | unknown |
| Ethnic differences | None known |
| Population | N/A |
| Ethnic incidence | N/A |
| Enzyme location | Converts 2-methylacetoacetyl-CoA to propionyl-CoA and acetyl-CoA. |
| Enzyme Function | Catalyzes the decarboxylation of oxoacids. |
| Missing Enzyme | Mitochondrial acetoacetyl-CoA thiolase enzyme |
| Metabolite changes | Increased urinary excretion of 2-methyl-3-hydroxybutyric acid, 2-methylacetoacetic acid, tiglylglycine, 2-butanone, and ketone bodies (acetoacetic acid, 3-hydroxybutyric acid). |
| Gene | ACAT1 |
| Gene location | 11q22.3-q23.1 |
| DNA testing available | Not in US. Sequencing of gene on a research basis. |
| DNA testing detail | No common mutation known |
| Prenatal testing | Enzyme analysis in amniocytes or CVS tissue. If mutations have been identified, DNA testing is possible. |
| MS/MS Profile | C5:1 tiglycarnitine – elevated |
| OMIM Link | www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=203750 |
| Genetests Link | www.genetests.org |
| Support Group | Organic Acidemia Association Save Babies through Screening Foundation |
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