Neurocognitive outcome in patients with hypertyrosinemia type I after long-term treatment with NTBC.

OBJECTIVE: The implementation of NTBC into treatment of hypertyrosinemia type I (HT I) greatly improved survival by prevention of acute liver failure and hepatocellular carcinoma. However, there are first reports of cognitive impairment in patients with elevated plasma tyrosine concentrations. METHODS: We here assess the neurocognitive development using standardized psychometric test batteries with respect to cognition, motor abilities and speech in nine early-treated patients with HT I under long-term NTBC treatment. RESULTS: High plasma tyrosine concentrations were frequently documented resulting in elevated 12-month median plasma tyrosine concentrations in seven out of nine patients. Plasma NTBC concentrations were generally in the lower therapeutic range. Five out of seven patients (71%) above 3 years of age had a total IQ score below the average. In addition, five out of seven patients above 3 years showed an inhomogenous test profile with significant differences between the different testing scales. Motor abilities were subnormal in four out of seven patients(57%). Cerebral MRI revealed no abnormalities. Logopedic evaluation in children at school age documented dysfunction or retardation in language development in all but one of the tested patients (80%), however, all but one patients had a migration background. CONCLUSIONS: A high number of patients performed below normal in the assessment of development, motor function and speech. We propose intellectual impairment as long-term complication in HT type I with elevated plasma tyrosine under NTBC treatment as observed in other hypertyrosinemias. These findings remain to be reproduced in greater patient numbers.

Longitudinal assessment of intellectual achievement in patients with classical galactosemia.

OBJECTIVE: To conduct a longitudinal assessment of long-term cognitive outcome in patients with classical galactosemia. METHODS: Inclusion criteria were (1) previous assessment of IQ dating back >10 years with tests being comparable with the recent German tests HAWIK-III and HAWIE-R, (2) absence of illnesses other than galactosemia, (3) absence of foreign language problems, (4) enzymatic-metabolic proof of classical galactosemia, (5) compliance with dietary therapy, and (6) written informed consent. Twenty-three patients who fulfilled these criteria were found. They underwent the first IQ test at a mean age of 11 +/- 5 years and the second 13.6 to 15.5 years later at a mean age of 26 +/- 5 years. Results were corrected for the obsolescence of test norms (Flynn effect). RESULTS: Mean total IQ scores on the first and second tests were 78 +/- 14 and 73 +/- 15, respectively, and not significantly different. IQ scores in the average range were observed for 7 patients on the first test and for 5 patients on the second test. For 17 patients, the intraindividual IQ scores remained essentially unchanged. Five patients showed a decrease and 1 an increase of the IQ score over time. No consistent pattern of change was found with respect to performance or verbal IQ subscores or in achievements in the individual subtest. CONCLUSIONS: The results confirm the presence of reduced cognitive ability in classical galactosemia and present evidence for an absence of substantial galactosemia-induced aggravation of this impairment with increasing age, at least in patients from 4 to 40 years of age. It remains to be clarified whether a reduction of cognitive function in galactosemia may be initiated by an in utero toxicity of endogenously formed galactose and which role such a process may play in the development of intellectual deficiencies that are later maintained throughout life.

Evaluation of quality of life and description of the sociodemographic state in adolescent and young adult patients with phenylketonuria (PKU).

BACKGROUND: Normal intellectual and personal development can be expected in early-diagnosed and treated PKU patients. Aim of the study was to analyse quality of life and social status, which are important parameters for an overall estimation of success of treatment apart from intellectual outcome in adult PKU patients. METHODS: 67 patients completed a questionnaire on quality of life and social status. Data was compared to the German census on an age matched control collective. RESULTS: Quality of life measured with the Profile of Quality of Life in the Chronically Ill (PLC) revealed mean values for capacity of performance in the patient group in the same range as in the control collective. The analysis of the social state of PKU patients revealed a tendency towards lower or delayed autonomy, and a low rate of forming normal adult relationships in which to have children. Schooling and professional career corresponded approximately to the control collective. CONCLUSION: Though every chronic disorder must be regarded as restraining, it shows that PKU does not preclude healthy emotional adjustment when the disease is diagnosed early and treated well.