Fatty Acid Oxidation Disorders |
|
| Disease Name | Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency |
| Alternate name(s) | N/A |
| Acronym | LCHADD/TFP |
| Disease Classification | Fatty Acid Oxidation Disorder |
| Variants | Yes |
| Variant name | Mitochondrial trifunctional protein deficiency |
| Symptom onset | Neonatal, infancy |
| Symptoms | Hypoketotic hypoglycemia, hypotonia, cardiomyopathy, hepatic disease, peripheral neuropathy and pigmentary retinopathy, rhabdomyolysis, sudden death |
| Natural history without treatment | Possible developmental delay due to damage from hypoglycemic episodes, possible death due to cardiomyopathy or hepatic failure. |
| Natural history with treatment | Intelligence is usually normal if there is no damage due to hypoglycemic crisis. Peripheral neuropathy, if present, may not improve with treatment. |
| Treatment | Avoidance of fasting, use of uncooked starch, MCT treatments, carnitine supplementation, DHA supplementation (may prevent retinopathy, but this has not been proven) |
| Other | Maternal complications in pregnancy include acute fatty liver of pregnancy, HELLP syndrome, and pre-eclampsia |
| Physical phenotype | Hypotonia, cardiomyopathy and possible retinal changes |
| Inheritance | Autosomal recessive |
| General population incidence | Rare |
| Ethnic differences | Yes |
| Population | Finnish |
| Ethnic incidence | 1:240 carrier rate for common mutation G1528C in Finland |
| Enzyme location | Inner mitochondrial membrane, liver, heart, fibroblasts |
| Enzyme Function | Metabolizes long chain fatty acids (C-12 to C-16 in length) |
| Missing Enzyme | Long-chain 3-hydroxyacyl-CoA dehydrogenase or mitochondrial trifunctional protein |
| Metabolite changes | Increased 3-hydroxydicarboxylic acids in urine, increased saturated and unsaturated 3-hydroxy organic acids, possible elevated CPK during acute illness. |
| Gene | HADHA and HADHB (alpha and beta subunits) |
| Gene location | 2p23 |
| DNA testing available | Yes – mutation analysis |
| DNA testing detail | Common mutation, G1528C, accounts for 87% of all mutant alleles in LCHAD deficiency; 70% of affected individuals will be homozygous for this mutation. There is no common mutation in trifunctional protein deficiency. |
| Prenatal testing | Enzyme analysis, protein analysis and direct DNA (when applicable). |
| MS/MS Profile | C18:OH, C16:1OH, C16OH |
| OMIM Link | http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600890 |
| Genetests Link | www.genetests.org |
| Support Group | FOD Family Support Group Save Babies through Screening Foundation |
|
|
