Tyrosinaemia type I (McKusick 276700) (Kvittingen 1991) is an autosomal recessively inherited metabolic disorder due to two enzymatic deficiencies: fumarylacetoacetase (FAH) (type Ia) and maleylacetoacetate isomerase (type Ib) (Berger et al 1988). Elevation of urinary succinylacetone (SA) is usually deemed to be specific for tyrosinaemia type I. Diagnosis is made by assessing plasma tyrosine levels and urinary SA and by determining the activity of FAH in fibroblasts or lymphocytes. We report the case of a 3-year-old female child affected by tyrosinaemia type Ia, with persistent low levels of plasma tyrosine and no excess of urinary SA. Maria M. was born to first-degree cousins; the postnatal period is reported as uneventful. At 7 months of age hepatomegaly was noted and the child was hospitalized. At that time plasma tyrosine was slightly elevated (425 #mol/L by ion exchange chromatography), with moderate tyrosinuria. No excess of SA was detectable in urine by GC-MS. c~-Fetoprotein serum level was > 300 IU/ml. Liver ultrasound and CT scans showed hepatomegaly and multifocal micronodular structural abnormalities. Tyrosinaemia type I was then suspected despite the absence of SA and a dietary regimen with low phenylalanine and tyrosine intake (25mg/kg per day) wasintroduced. One month later, plasma tyrosine level was in the normal range (100/~mol/L). The clinical picture has always been good, including adequate psychomotor development, except for a marked hepatomegaly (4 cm below the costal arch); plasma tyrosine was steadily below l l0/tmol/L with only a slight elevation of plasma methionine; a major biochemical abnormality was c~-fetoprotein 4232 IU/ml (normal 0.01-7.00). On the basis of the good metabolic control, diet was then progressively relaxed in order to assess her dietary tyrosine tolerance (up to 100mg/kg per day). Plasma tyrosine levels remained constantly below 160 #mol/L, even 3 h after a meal. Urinary SA was still absent. Tyrosinaemia was then monitored for 1 year on a relaxed diet, being ...