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
http://www.nucdf.org

National Coalition for PKU and Allied Disorders
http://www.pku-allieddisorders.org/

Children Living with Inherited Metabolic Diseases
http://www.climb.org.uk/

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