Effect on intelligence of relaxing the low phenylalanine diet in phenylketonuria.

Abstract

A total of 599 children with phenyketonuria, who had been treated early, were followed up prospectively in order to examine the association between intellectual progress from 4 to 14 years of age and control of phenylalanine concentrations. The phenylalanine rose from around 400 imol/l during the first four years to above 900 ,mol/l by 12 years. The Subjects and methods SUBJECTSThe subjects in the study were followed up prospectively by the staff of the Phenylketonuria Register using the protocol described previously.' 2 7 8 This included serial blood phenylalanine concentrations, a record of the dietary intake of phenylalanine and phenylalanine-low protein substitute at each birthday, and standardised psychological assessments at 4, 8, 10, 12, and 14 years. Subjects were selected for the present study if they had been treated before 4 months of age, were over 10 years of age (born 1964 to 1978), and had completed the follow up protocol to 8 years of age. At the time of the study data for those aged 9 years and over was still being collected in cohort II. Children treated for less than 1 year because they proved to have mild phenylketonuria were excluded, as were those with tetrahydrobiopterin deficiency or whose mothers had phenylketonuria.Altogether 599 subjects fulfilled the study criteria and were divided into two cohorts: those born 1964-71 (cohort I, 224 subjects) before reorganisation of the national screening programme,' and those born 1972-78 (cohort II, 375 patients). Eighty nine children previously studied at 4 years2 were excluded from the present study because they had no valid IQ at 8 years (39 in cohort I, 50 in cohort II), usually because testing was incomplete, outside the age limits, or the test used was other than that specified. Subjects included in the study represent 53% (cohort I) and 80% (cohort II) of all known early treated subjects in the United Kingdom compared with 63% and 89% studied at 4 years. The loss of subjects between 4 and 8 years may have exerted a slight upward bias in overall IQ as children assessed at 4 but not at 8 had a lower mean IQ than those assessed on both occasions. However, the size of the bias 311 on 11 May 2018 by guest. Protected by copyright.

Management of Phenylketonuria for Optimal Outcome: A Review of Guidelines for Phenylketonuria Management and a Report of Surveys of Parents, Patients, and Clinic Directors

“…Many reports have shown that optimum outcome occurs when dietary therapy is started early and continued indefinitely. 22,[25][26][27][28][29][30][31][32][33][34][35][36] As with other chronic illnesses, decreased compliance and poor dietary control increase with age, especially after 6 years of age. 17,25,37,38 Older individuals who have discontinued dietary therapy are at risk for developing loss of intelligence, magnetic resonance imaging findings consistent with white matter dysfunction, and occasionally acute demyelinating neuropathies.…”

Randomised controlled trial of essential fatty acid supplementation in phenylketonuria

“…However, even in patients who are well controlled during childhood, neurological deterioration has been observed (Villasana et al, 1989;Thompson et al, 1990;Cleary et al, 1994;Weglage et al, 1995) and children with PKU have, on average, an IQ score that is 0.5 s.d. less than the general population (Smith et al, 1991). The reason for this may be the effects of raised phe on brain myelination but the relative deficiency of DHA supply may also contribute to a poorer intellectual outcome (Cockburn et al, 1996).…”

Fenilquetonuria de diagnóstico neonatal y lactancia materna

“…Sin embargo, para prevenir el retardo mental a largo plazo, es necesario realizar el seguimiento médico, nutricional, bioquímico, neurológico y psicológico perió-dicos y permanentes 15,16 .…”

“…Iniciar el tratamiento precozmente y mantener el nivel de FA en sangre bajo 10 mg/dl (600 µmol/ l) permite un desarrollo mental normal [15][16][17] . Los resultados de este estudio, demuestran que a los 4 y 6 meses de edad, 13 de los 16 pacientes evaluados (81%) tenían MDI y PDI normal.…”