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Tyrosinemia type 3
Disease definition
A rare inborn error of tyrosine metabolism characterized by mild hypertyrosinemia and increased urinary excretion of 4-hydroxyphenylpyruvate, 4-hydroxyphenyllactate and 4-hydroxyphenylacetate.
ORPHA:69723
Classification level: Disorder- Synonym(s):
- Tyrosinemia due to 4-hydroxyphenylpyruvate dioxygenase deficiency
- Tyrosinemia due to 4-hydroxyphenylpyruvic acid oxidase deficiency
- Tyrosinemia due to HPD deficiency
- Tyrosinemia type III
- Prevalence: <1 / 1 000 000
- Inheritance: Autosomal recessive
- Age of onset: Infancy, Neonatal
- ICD-10: E70.2
- ICD-11: 5C50.1Y
- OMIM: 276710
- UMLS: C0268623
- MeSH: -
- GARD: 10332
- MedDRA: 10069461
Summary
Epidemiology
It is the least frequent form of tyrosinemia with less than 20 cases reported in the literature so far.
Clinical description
The clinical picture is highly variable ranging from asymptomatic in some patients identified through neonatal screening program studies to patients with neurologic manifestations including intellectual deficit, ataxia, tremors and seizures.
Etiology
Tyrosinemia type 3 is caused by mutations in the HPD gene (12q24.31) encoding 4-hydroxyphenylpyruvate dioxygenase.
Diagnostic methods
Detection of elevated tyrosine in the blood and detection of tyrosine derivatives in the urine is suggestive of the disease. The diagnosis is confirmed by enzyme assay, revealing accumulation of 4-hydroxyphenylpyruvate dioxygenase in the liver or kidney, or by mutation testing.
Differential diagnosis
The differential diagnosis broadly includes neurological disorders with psychomotor and/or intellectual disability of other etiology.
Antenatal diagnosis
Antenatal diagnosis is possible when a disease-causing mutation has been identified in the family.
Genetic counseling
Tyrosinemia type 3 is an autosomal recessive disorder. Genetic counseling should be offered to at-risk couples (both individuals are carriers of a disease-causing mutation) informing them there is a 25% chance of having an affected child at each pregnancy.
Management and treatment
Although it has not been clearly established that treatment prevents the onset of symptoms, it is currently recommended that, patients with tyrosinemia type 3 follow a phenylalanine- and tyrosine-restricted diet.
Prognosis
Tyrosinemia type 3 has no impact on life expectancy. Intellectual disability, usually mild to moderate, may require adaptations to daily life.
A summary on this disease is available in Deutsch (2010) Español (2010) Français (2010) Italiano (2010) Nederlands (2010) Português (2010) Greek (2010, pdf) Polski (2010, pdf) Polski (2010)
Additional information