HEREDITARY TYROSINEMIA TYPE-I - A LONG-TERM STUDY OF THE RELATIONSHIPBETWEEN THE URINARY EXCRETIONS OF SUCCINYLACETONE AND DELTA-AMINOLEVULINIC-ACID

Patients with hereditary tyrosinaemia type I(HT) excrete large amounts of succinylacetone (SA) in urine. Owing to structural resemblance of SA to delta-aminolevulinic acid (ALA), SA inhibits the second enzyme i n the pathway for haeme biosynthesis, porphobilinogen synthase, result ing in increased urinary ALA excretion. We investigated the relationsh ip between urinary SA and ALA excretions of two patients with differen t forms of HT (late-infantile and juvenile). In both patients the urin ary SA and ALA excretions showed a more or less inverse correlation. T he patient with the early-infantile form of HT had a relatively greate r increase in urinary SA and ALA excretions in comparison to the patie nt with the juvenile form of HT. A possible explanation for this unexp ected inverse correlation between the urinary excretion of SA and ALA might be a lack of intramitochondrial glycine, a substrate for delta-a minolevulinic acid synthesis. It has been reported previously that hig h concentrations of SA reversibly and competitively inhibit the transp ort of glycine through membranes.