Increased excretion of coproporphyrin I in a patient with hereditary tyrosinaemia type I: Relevant changes with NTBC treatment

Hereditary tyrosinaemia type I (HTT-I ; McKusick 27670) is an autosomal recessive disorder caused by a deficiency of the enzyme fumarylacetoacetate hydrolase (EC 3.7.1.2). The main symptoms include hepatic and renal dysfunction and sometimes neurological crisis. It is characterized by increased plasma levels of tyrosine and methionine, and excessive urinary excretion of p-hydroxyphenylacids, tyrosine, succinylacetone and δ-aminolevulinic acid. The presence of succinylacetone in biological samples is diagnostic for this condition (Mitchell et al 1995). Most patients show a partial response to dietary restriction of phenylalanine and tyrosine. Further improvement might be obtained by liver transplantation, although production of toxic metabolites may persist (Laine et al 1995). Inhibition of 4-hydroxyphenylpyruvate dioxygenase by 2-(2-nitro-4-trifluoromethylbenzoyl) cyclohexane-1,3-dione (NTBC) prevents the formation of the potentially toxic products. Treatment with NTBC has been shown to be superior to dietary treatment and liver transplantation (Lindstedt et al 1992). The disturbance of porphyrin metabolism in HTT-I is ascribed to the role of succinylacetone as an inhibitor of the δ-aminolevulinic acid dehydratase, the activity of which is greatly reduced in liver and erythrocytes. Coproporphyrin (CP) is by far the most common porphyrin excreted in secondary alteration in the haem biosynthetic pathway. CP has four isomers, but only CP I and CP III isomers are detected in urine. The aim of the present study was to determine whether other places along the haem pathway than δ-aminolevulinic acid dehydratase might be affected in HTT-I and to assess the influence of treatment with NTBC on porphyrin synthesis. We studied the coproporphyrinuria of a female patient who is undergoing NTBC treatment.