Mutations in the 4-hydroxyphenylpyruvate dioxygenase gene (HPD) in patients with tyrosinemia type III

Tyrosinemia type III (OMIM 276710) is an autosomal recessive disorder cause d by the deficiency of 4-hydroxyphenylpyruvate dioxygenase (HPD), the secon d enzyme in the tyrosine catabolic pathway. The enzyme deficiency results i n an accumulation and increased excretion of tyrosine and phenolic metaboli tes. Only a few cases with the disorder have been described, and the clinic al spectrum of the disorder is unknown. Reported patients have presented wi th mental retardation or neurological symptoms or have been picked up by ne onatal screening. We have identified four presumed pathogenic mutations (tw o missense and two nonsense mutations) in the HPD gene in three unrelated f amilies encompassing Four homozygous individuals and one compound heterozyg ous individual with tyrosinemia type III. Furthermore, a number of polymorp hic mutations have been identified in the HPD gene. No correlation of the s everity of the mutation and enzyme deficiency and mental function has been found; neither do the recorded tyrosine levels correlate with the clinical phenotype.