Trabecular bone mineral content was assessed by quantitative computed tomography in eleven young adults with phenylketonuria who had been treated from early childhood with a diet restricted in natural protein and supplemented with amino acids, minerals and vitamins. There was a significant reduction in the bone mineral content of patients compared with the normal population. Prospective studies are indicated in younger patients to ensure optimum bone mineralisation is achieved by adulthood.

Background-Associations between genotype and intellectual outcome in patients with phenylketonuria are complicated because intelligence is influenced by many variables, including environmental factors and other genetic determinants. Intellectual changes with age, both on and after relaxation of diet, vary within the patient population. This study aims to determine whether a significant association exists between genotype and change in intelligence after relaxation of diet. Methods-125 patients with hyperphenylalaninaemia and phenylketonuria whose diet was relaxed after 8 years of age. Verbal, performance, and full scale intelligence quotients at 8, 14, and 18 years were expressed as standard deviation scores (IQ-SDS), and genotype as predicted residual enzyme activity (PRA) of phenylalanine hydroxylase. Results-IQ-SDS at 8, 14, and 18 years were significantly below normal; no association was found between PRA and IQ-SDS. Significant reductions in verbal and full scale IQ-SDS occurred between 8 and 14 years and 8 and 18 years. There was a significant association between PRA and the reduction in verbal, performance, and full scale IQ between these years. Multiple regression analysis of 18 year results, using 8 year results as covariates, supported the association between PRA and IQ-SDS; after adjustment for phenylalanine control, both up to and after the age of 8 years, the full scale IQ-SDS at 14 and 18 years was 0.15 higher for each 10% increase in PRA. Conclusions-Genotype might be useful in predicting the likelihood of intellectual change in patients with hyperphenylalaninaemia and phenylketonuria whose diet is relaxed after the age of 8 years. (Arch Dis Child 2000;82:216-221)

A radiograph of the left hand and wrist was taken in 141 children and young adults with phenylketonuria and hyperphenylalaninaemia. Ten (7.1%) had a bony abnormality and, of these, six (4.3%) showed evidence of reduced bone density. Only one patient had evidence of spiculation of the lower ulnar metaphysis previously described in phenylketonuria. Bone maturity was also assessed in 130 patients by the Tanner-Whitehouse (TW2) method. In 28 patients (21.5%) bone age was less than chronological age by 1 year or more. Bone age delay was greater in younger children on a more restricted diet with a lower intake of natural protein.

Tetrahydrobiopterin (BH4) deficiency is a rare cause of hyperphenylalaninaemia (HPA) and usually leads to progressive neurological deterioration despite early dietary control of plasma phenylalanine concentrations. Dihydropteridine reductase (DHPR) deficiency is the most severe cause with respect to a fatal outcome. We report a 7-year-old girl with HPA diagnosed on neonatal Guthrie screening who at the age of 6 months had cytotoxic therapy for an adrenal neuroblastoma which secreted catecholamines. When 4 years old she was found to have DHPR deficiency. Although developmentally retarded and microcephalic she has failed to develop the florid neurological features often associated with the condition.

We report five cases of peptic ulceration in patients with classical phenylketonuria and suggest that there may be a causal relationship between the two conditions. Peptic ulceration is a relatively uncommon disorder of children and young adults.' Of the 180 patients with phenylketonuria (PKU) in Northern Ireland who have been diagnosed since 1954, five are known to have developed peptic ulceration which presented between 11 and 25 years of age. Two presented with haematemesis, one with perforation, one with melaena and one with abdominal pain and vomiting. None was on a strict diet at the time of presentation and plasma phenylalanine concentrations were high. Four were not receiving supplements of amino acids. Case histories PATIENT 1 This mentally retarded woman lives at home and attends a day centre. Phenylketonuria was diagnosed when she was 10 months old. At the age of 21 years she was admitted to hospital with haematemesis requiring blood transfusion. There was a history of epigastric pain at night for 12 months and vomiting for six months. At the time of her admission she was on a protein restricted diet and an amino acid supplement as treatment for her PKU. On barium meal there was considerable increase in the amount of resting juice, with deformity, spasm and a small ulcer crater in the duodenal cap.