ABSTRACT
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.
Subject(s)
Intelligence Tests , Intelligence/genetics , Phenylalanine Hydroxylase/genetics , Phenylketonurias/diet therapy , Phenylketonurias/genetics , Adolescent , Age Factors , Child , Female , Genotype , Humans , Male , Mutation , Phenylalanine Hydroxylase/analysis , Phenylketonurias/enzymology , Predictive Value of TestsABSTRACT
Parent or self-reported history of fractures in a group of patients aged from 0.3 to 33.6 years on dietary treatment for phenylketonuria was studied by means of a questionnaire. Twenty-one of 85 patients had a history of fracture compared with 18/98 sibling controls. There was no significant difference in the lifetime risk of fracture between patients and controls (chi 2 = 1.43, df = 1, p = 0.23), but a significantly higher risk of fracture was reported over the age of 8 y (chi 2 = 5.11, df = 1, p = 0.024), with a relative risk of 2.6 (95% confidence interval 1.1.6.1). We suggest this may be related either to deterioration in dietary control in this age group or to a cumulative disease-related or diet-related reduction in bone mass.
Subject(s)
Fractures, Bone/complications , Phenylketonurias/complications , Adolescent , Adult , Age Factors , Bone Density , Child , Child, Preschool , Diet Therapy/adverse effects , Fractures, Bone/etiology , Humans , Infant , Phenylketonurias/therapy , Risk FactorsABSTRACT
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.
Subject(s)
Hand/diagnostic imaging , Phenylalanine/blood , Phenylketonurias/diagnostic imaging , Wrist Joint/diagnostic imaging , Adolescent , Adult , Age Determination by Skeleton , Bone Density , Bone Development , Bone and Bones/diagnostic imaging , Child , Child, Preschool , Female , Humans , Infant , Male , Phenylketonurias/blood , Phenylketonurias/diet therapy , Phenylketonurias/physiopathologySubject(s)
Heart/physiology , Phenylketonurias/physiopathology , Selenium/blood , Adolescent , Adult , Age Factors , Child , Child, Preschool , Electrocardiography , Humans , Phenylketonurias/bloodABSTRACT
Selenium deficiency is a frequent finding in children with phenylketonuria (PKU) receiving dietary treatment. We report the occurrence of episodic ventricular tachycardia in a 9-month-old infant with PKU. Serum selenium (Se), 0.13 mumol/l (normal range 0.28-1.12 mumol/l, mean +/- 2 SD), and whole blood glutathione peroxidase (GSHPX), 16 U/g Hb (normal range 19.5-34.3 U/g Hb, mean +/- 2 SD), were low. Auscultation of cardiac rhythm is recommended during the routine follow-up of young children with PKU. Se deficiency should be considered in the aetiology of a dysrhythmia and corrected with Se supplementation.
Subject(s)
Phenylketonurias/diet therapy , Selenium/deficiency , Tachycardia/etiology , Diet Therapy/adverse effects , Humans , Infant , Male , Phenylketonurias/complications , Tachycardia/complicationsABSTRACT
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.
Subject(s)
Adrenal Gland Neoplasms/complications , Neuroblastoma/complications , Phenylketonurias , Adrenal Gland Neoplasms/metabolism , Biopterins/analogs & derivatives , Biopterins/biosynthesis , Catecholamines/biosynthesis , Child , Coenzymes/biosynthesis , Female , Humans , Neuroblastoma/metabolism , Phenylalanine/metabolism , Serotonin/metabolismABSTRACT
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.
Subject(s)
Bone Density , Bone Diseases, Metabolic/etiology , Phenylketonurias/diagnostic imaging , Adult , Bone Diseases, Metabolic/diagnostic imaging , Bone Diseases, Metabolic/pathology , Diet/adverse effects , Female , Humans , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/pathology , Male , Phenylketonurias/diet therapy , Phenylketonurias/pathology , Tomography, X-Ray ComputedABSTRACT
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.
