ABSTRACT
Even early-treated phenylketonurics may suffer from phenylalanine-related deficits. Elevated phenylalanine concentrations can interfere with the development and function of the CNS. Outcome beyond childhood has not been extensively investigated. This long-term study was performed to determine whether adolescents and young adults with PKU show frontal lobe-dependent deficits when compared to diabetic patients. The comparative study covered 35 PKU patients, 13-21 years of age (mean 17.8 years), and 35 diabetic patients matched for sex, age and socioeconomic status. Patients were assessed for IQ (Culture Fair Intelligence Test), information processing (Trail Making Test), and selective and sustained attention (Stroop Task, Test d-2). Assessments were repeated within a 3-year follow-up. PKU patients showed no increase in blood phenylalanine concentrations at follow-up. They had significantly poorer test results than the diabetic patients at both assessment times. Within the tests, however, this was due to reduced performance speed but not to deficits in specific frontal lobe-dependent functions. Elevated phenylalanine concentrations seem to exert a global effect slowing performance speed. This effect is enduring in adolescence and early adulthood.
Subject(s)
Frontal Lobe/pathology , Phenylalanine/blood , Phenylketonurias/diagnosis , Adolescent , Adult , Amino Acid Metabolism, Inborn Errors/blood , Amino Acid Metabolism, Inborn Errors/diagnosis , Amino Acid Metabolism, Inborn Errors/physiopathology , Analysis of Variance , Central Nervous System/pathology , Diabetes Mellitus/blood , Female , Humans , Intelligence , Intelligence Tests , Male , Neuropsychological Tests , Phenylketonurias/blood , Phenylketonurias/physiopathology , Social Class , Time FactorsABSTRACT
BACKGROUND: Cognitive impairment and fine motor deficits are frequent manifestations in patients with neurofibromatosis type 1 (NF1). More than 50% of patients with NF1 show focal areas of high signal intensity (T2H) on T2-weighted MRI of the brain. It has been hypothesized that T2H may be associated with the cognitive and motor problems. METHODS: The authors investigated 100 patients with NF1 and 100 healthy control subjects matched for age, sex, and socioeconomic status for their IQ (Wechsler Intelligence Scale for Children-Revised [WISC-R] and Wechsler Adult Intelligence Scale-Revised [WAIS-R]), fine motor abilities (Motorische Leistungs-Serie [motor performance task]), and T2H (MRI). RESULTS: As a group, the 100 patients performed within normal limits of WISC-R and WAIS-R scores. However, the scores for the NF1 patients with normal MRI were at the mean, whereas those for the patients who had T2H (n = 58) were significantly depressed. On measures of fine motor skills, patients with T2H performed poorer than patients with normal MRI. CONCLUSION: Hyperintensities on T2-weighted MRI represent a biological marker for impaired cognitive and fine motor performance in patients with NF1.
Subject(s)
Cognition Disorders/diagnosis , Motor Skills , Neurofibromatosis 1/diagnosis , Adolescent , Adult , Biomarkers , Brain/pathology , Child , Cognition Disorders/complications , Female , Follow-Up Studies , Humans , Magnetic Resonance Imaging , Male , Neurofibromatosis 1/complications , Neuropsychological Tests , Predictive Value of Tests , Reference Values , Social Class , Wechsler ScalesABSTRACT
In a group of 87 consecutive patients with hyperphenylalaninaemia born since 1990, only 3 patients showed a (temporary) decrease of serum phenylalanine levels after tetrahydrobiopterin (BH4) loading in usual doses (20 mg/kg body weight).
Subject(s)
Biopterins/analogs & derivatives , Biopterins/therapeutic use , Phenylketonurias/drug therapy , Female , Humans , Infant, Newborn , Male , Neonatal Screening , Phenylalanine/blood , Phenylalanine Hydroxylase/blood , Phenylalanine Hydroxylase/deficiency , Retrospective StudiesABSTRACT
Even early-treated patients with phenylketonuria (PKU) have a higher risk of psychosocial maladjustment. This study was performed to determine whether emotional and behavioural problems are specific in phenylketonurics and whether they depend on the quality of biochemical control. This comparative study covered 42 PKU patients aged 10-18 years (mean 14.7 years) and 42 diabetic patients matched for sex, age and socioeconomic status. Patients' groups were compared with a control sample of healthy controls (n = 2900) from an epidemiological study. We used the Child Behavior Check List (CBCL) according to Achenbach, intelligence quotient (IQ) test according to Weiss, and monitoring of blood phenylalanine concentrations and HBA1 concentrations. Internalizing problems such as depressive mood, anxiety, physical complaints or social isolation were significantly elevated in both phenylketonuric and diabetic patients, whereas externalizing problems were not. The two patient groups did not differ significantly either in the degree or in the pattern of their psychological profile. In both groups no significant correlations could be computed between the psychological characteristics and the biochemical control, the IQ, and the socioeconomic status. No patient was undergoing psychiatric treatment or psychotherapy. Our results strongly support a psychological perspective for the development of behavioural and emotional problems in both phenylketonuric and diabetic patients. Thus, medical treatment should be accompanied by psychological support for the families.
Subject(s)
Phenylketonurias/psychology , Adolescent , Adolescent Behavior , Affective Symptoms/etiology , Case-Control Studies , Child , Diabetes Mellitus, Type 1/psychology , Female , Humans , Male , Mental Disorders/etiology , Phenylalanine/blood , Phenylketonurias/complications , Phenylketonurias/diet therapyABSTRACT
Even early-treated phenylketonuric patients suffer from phenylalanine-associated (mild) neuropsychological impairment. To date it is still unclear whether patients' deficits show a progression on ageing. This unsolved question seems to be an important aspect in the still ongoing debate about how long and how strictly the patients should be maintained on diet. Twenty early-treated (20 +/- 10, 9-30 days) adolescent phenylketonurics (10 boys, 10 girls) and 20 healthy controls, matched for age, sex and IQ, were investigated twice at a mean ages of 11 and 14 years for their IQ (Culture Fair Intelligence Test-Scale 2; CFT-20), fine motor abilities (Motor Performance Task), sustained (Test d2) and selective attention (Stroop-Task). At the first test, examinations revealed significant blood phenylalanine-correlated neuropsychological deficits in PKU patients. In spite of raised blood phenylalanine concentrations during the following 3 years and significantly elevated concurrent blood phenylalanine concentrations, the repeated measurements revealed a significant decrease of patients' deficits compared to controls. Clinical-neurological status of patients and controls was normal at both test times. The results indicate a decreased vulnerability of PKU-patients with respect to their neuropsychological functioning against elevated blood phenylalanine levels on ageing.
