Amino Acid Disorders |
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| Disease Name | Tyrosinemia, type 1 |
| Alternate name(s) | Hereditary infantile tyrosinemia, Hepatorenal tyrosinemia, Fumarylacetoacetase deficiency, Fumarylacetoacetate hydrolase |
| Acronym | FAH deficiency |
| Disease Classification | Amino Acid Disorder |
| Variants | Yes |
| Variant name | Tyrosinemia I chronic-type, Tyrosinemia II, Tyrosinemia III |
| Symptom onset | Infancy |
| Symptoms | Hepatocellular degeneration leading to acute hepatic failure or chronic cirrhosis and hepatocellular carcinoma, renal Fanconi syndrome, peripheral neuropathy, seizures and possible cardiomyopathy. |
| Natural history without treatment | Chronic liver disease leading to cirrhosis and hepatocellular carcinoma. Renal tubular disease (Fanconi syndrome) with phosphaturia, aminoaciduria and often glycosuria. May lead to clinical rickets. Peripheral neuropathy. Self-injurious behavior, seizures and cardiomyopathy have been observed. Coagulation problems. |
| Natural history with treatment | Hepatitic disease may progress despite dietary treatment. NTBC treatment leads to improvements in kidney, liver and neurologic function, but may not affect incidence of liver cancer. |
| Treatment | Dietary restriction of phenylalanine and tyrosine. NTBC (2-(2-nitro-4-trifluoro-methylbenzoyl)-1,3-cyclohexanedione) treatment which improves hepatic and renal function. Liver transplantation when indicated to prevent hepatocellular carcinoma. Vitamin D to heal rickets. |
| Other | Unpleasant odor due to accumulation of methionine. Sometimes described as “cabbage-like” odor. |
| Physical phenotype | No abnormalities present at birth. May develop widely-spaced incisors, pes planus, epicanthus and microcephaly. |
| Inheritance | Autosomal recessive |
| General population incidence | 1:100,000 |
| Ethnic differences | Yes |
| Population | French Canadian (Saquency-Lac Saint Jean region) 1:20 carrier rate |
| Ethnic incidence | 1:1846 |
| Enzyme location | Liver, kidney, lymphocytes, fibroblasts |
| Enzyme Function | Metabolizes fumarylacetoacetic acid into fumaric acid and acetoacetic acid |
| Missing Enzyme | Fumarylacetoacetate hydrolase |
| Metabolite changes | Increased urinary succinylacetone, increased tyrosine and methionine in serum, increased alpha fetoprotein. |
| Gene | FAH |
| Gene location | 15q23-25 |
| DNA testing available | Yes |
| DNA testing detail | DNA for isolated populations |
| Prenatal testing | Enzymatic assay of amniocytes or CVS cells. Direct DNA testing in amniocytes or CVS cells if mutations known. Succinylacetone in amniotic fluid. |
| MS/MS Profile | N/A |
| OMIM Link | http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=276700 |
| Genetests Link | www.genetests.org |
| Support Group | National Urea Cycle Disorders Foundation National Coalition for PKU and Allied Disorders |
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