36 HEREDITARY TYROSINEMIA WITH UNUSUAL PHENOTYPIC EXPRESSION

Abstract

In the chronic form of tyrosinemia renal tubular dysfunction with secondary hypophosphatemic rickets usually is a major finding. Three patients, two brothers and one girl, had at the age of 5,12 and 15 years no generalized hyperaminoaciduria, nor clinical signs of rickets. Untreated the elder brother had only slightly elevated serum tyrosine, 141 μmol (normal <80), and low excretion of p-OH-phenyllactate. He had pronounced trorribocytopenia (8×109/l). The brother presented 21 months old with large liver. Serum tyrosine was 318 μmol/l, the trombocyte count 48×109/l. Succinylacetone was elevated in urine in both. The third patient was investigated for hepatomegaly in infancy, but developed normally without treatment until she contracted hepatoma at the age of 15 years. Her plasma tyrosine level was 600 - 700 μmol/l, she excreted large amounts of p-OH-phenyllactate and succinylacetone in urine was low but elevated, 8 mol creatinine. The fumarylacetoacetase activity in fibroblasts from both brothers and in lymphocytes from the girl was less than 5 % of normal level. Lack of renal tubular dysfunction in patients with the chronic form of tyrosinemia, is unusual. However, absence of this finding should not preclude the search for this diagnosis in patients otherwise suspected for hereditary tyrosinemia.