A new metabolic disorder characterised by the excessive excretion of beta-alanine, 3-hydroxypropionic acid, R- and S-3-amino- and 3-hydroxyisobutyric acids and S-2-(hydroxymethyl)butyric acid is probably due to deficient activities of malonic, methylmalonic and ethylmalonic semialdehyde dehydrogenases. These dehydrogenation reactions could be mediated by one enzyme, or by enzymes with a common subunit, and both R- and S-methylmalonic semialdehydes seem to be equally affected. The patient is now aged 4 years and has developed normally. He has a persistent gross hypermethioninaemia which is probably unrelated to the other biochemical abnormalities.

Tyrosinaemia type I (TT I) (McKusick 276700) is a heterogeneous disorder with a broad spectrum of clinical phenotypes. Although histological abnormalities of the pancreas are well recognized, there are only incidental reports of pancreatic dysfunction manifested as insulin-dependent diabetes mellitus. We report three subjects with TT I and acute liver dysfunction who had hyperinsulinism in early infancy. Hypoglycaemia persisted despite dietary treatment and one patient had inadequate lipolysis at the time of hypoglycaemia. All three patients were successfully treated with diazoxide (10 mg/kg per day) and chlorthiazide (35 mg/kg per day) and treatment was gradually withdrawn after 9, 13 and 34 months, respectively. The mechanism of pancreatic dysfunction in TT I is unknown but may be related to the toxic metabolites that accumulate in this condition. We conclude that hyperinsulinism is not a rare complication in TT I. In patients with persistent hypoglycaemia, C-peptide should always be measured. Treatment with diazoxide and chlorthiazide is highly effective, appears to be safe, and does not need to be continued lifelong.

Tyrosinaemia type III is a rare disorder caused by a deficiency of 4-hydroxyphenylpyruvate dioxygenase, the second enzyme in the catabolic pathway of tyrosine. The majority of the nine previously reported patients have presented with neurological symptoms after the neonatal period, while others detected by neonatal screening have been asymptomatic. All have had normal liver and renal function and none has skin or eye abnormalities. A further four patients with tyrosinaemia type III are described. It is not clear whether a strict low tyrosine diet alters the natural history of tyrosinaemia type III, although there remains a suspicion that treatment may be important, at least in infancy.

A patient presenting with a condition resembling Reye's syndrome was found to have a urinary organic acid excretion pattern similar to those previously described in a single patient with ethylmalonic-adipic aciduria. The present patient responded clinically to riboflavin supplementation and his fibroblasts, when cultured in riboflavin-depleted medium, showed an abnormal reduction in the rate of butyrate oxidation.

Aims-To assess the incidence of tyrosinaemia type I in the West Midlands Region, and the value of current neonatal screening programmes for phenylketonuria (PKU) for its detection.