SELECTED JOURNAL ARTICLES ON TYROSINEMIA TYPE III (always updating web addresses-may need to cut/paste URL another page)
Tyrosinemia Type III - Diagnosis And Ten-Year Follow-Up
Cerone R. Holme E. Schiaffino MC. Caruso U. Maritano L. Romano C. Source
Acta Paediatrica. 86(9):1013-1015, 1997 Sep.
Tyrosinemia type III, caused by deficiency of 4-hydroxyphenylpyruvate
dioxygenase, is a rare disorder of tyrosine catabolism. Primary
4-hydroxyphenylpyruvate dioxygenase deficiency has been described in only
three patients. The biochemical phenotype shows hypertyrosinemia and
elevated urinary excretion of 4-hydroxyphenyl derivatives. We report the
clinical and biochemical findings and the results of long-term follow-up
in a new patient with this disorder presenting with severe mental
retardation and neurological abnormalities. The clinical phenotype is
compared with those reported in the three previously described patients.
[References: 14]
Reprint available from:
Cerone R
UNIV GENOA
G GASLINI INST
DEPT PAEDIAT
LARGO G GASLINI 5
I-16148 GENOA
ITALY
GOTHENBURG UNIV
DEPT CLIN CHEM
S-41124 GOTHENBURG
SWEDEN
Identification of Point-mutations in the 4-Hydroxyphenylpyruvate Dioxygenase (4HPPD) Gene in Patients with Tyrosinemia type III. Rüetschi U, Schiaffino M C, Cerone R, Pérez-Cerda C, Ugarte M and Holme E. J. Inher. Metab. Dis. 20 Suppl 1, 14. http://www.sahlgrenska.medfak.gu.se/KKoT/Homepages/Publikationer/RuetAbst/JIEM97.html Hum Genet. 2000 Jun;106(6):654-62
Mutations in the 4-hydroxyphenylpyruvate dioxygenase gene (HPD) in patients with tyrosinemia type III.
Ruetschi U, Cerone R, Perez-Cerda C, Schiaffino MC, Standing S, Ugarte M, Holme E
Department of Clinical Chemistry and Transfusion Medicine, Goteborg University, Sahlgrenska University Hospital, Sweden. Ulla.Ruetschi@clinchem.gu.se
Tyrosinemia type III (OMIM 276710) is an autosomal recessive disorder caused by the deficiency of 4-hydroxyphenylpyruvate dioxygenase (HPD), the second enzyme in the tyrosine catabolic pathway. The enzyme deficiency results in an accumulation and increased excretion of tyrosine and phenolic metabolites. Only a few cases with the disorder have been described, and the clinical spectrum of the disorder is unknown. Reported patients have presented with mental retardation or neurological symptoms or have been picked up by neonatal screening. We have identified four presumed pathogenic mutations (two missense and two nonsense mutations) in the HPD gene in three unrelated families encompassing four homozygous individuals and one compound heterozygous individual with tyrosinemia type III. Furthermore, a number of polymorphic mutations have been identified in the HPD gene. No correlation of the severity of the mutation and enzyme deficiency and mental function has been found; neither do the recorded tyrosine levels correlate with the clinical phenotype. PMID: 10942115, UI: 20395563
Mutations in the 4-hydroxyphenylpyruvic acid dioxygenase gene are responsible for tyrosinemia type III and hawkinsinuria.
Tomoeda K, Awata H, Matsuura T, Matsuda I, Ploechl E, Milovac T, Boneh A, Scott CR, Danks DM, Endo F.
Department of Pediatrics, Kumamoto University School of Medicine, Kumamoto, Japan.
The enzyme 4-hydroxyphenylpyruvic acid dioxygenase (HPD) catalyzes the reaction of 4-hydroxyphenylpyruvic acid to homogentisic acid in the tyrosine catabolism pathway. A deficiency in the catalytic activity of HPD may lead to tyrosinemia type III, an autosomal recessive disorder characterized by elevated levels of blood tyrosine and massive excretion of tyrosine derivatives into urine. It has been postulated that hawkinsinuria, an autosomal dominant disorder characterized by the excretion of 'hawkinsin,' may also be a result of HPD deficiency. Hawkinsin is a sulfur amino acid identified as (2-l-cystein-S-yl, 4-dihydroxycyclohex-5-en-1-yl)acetic acid. Patients with hawkinsinuria excrete this metabolite in their urine throughout their life, although symptoms of metabolic acidosis and tyrosinemia improve in the first year of life. We performed analyses of the HPD gene in a patient with tyrosinemia type III and two unrelated patients with hawkinsinuria. A homozygous missense mutation predicting an Ala to Val change at codon 268 (A268V) in the HPD gene was found in the patient with tyrosinemia type III. A heterozygous missense mutation predicting an Ala to Thr change at codon 33 (A33T) was found in the same HPD gene in the two patients with hawkinsinuria. These findings support the hypothesis that alterations in the structure and activity of HPD are causally related to two different metabolic disorders, tyrosinemia type III and hawkinsinuria. Copyright 2000 Academic Press. PMID: 11073718 [PubMed - indexed for MEDLINE] updated 5/15/2005
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