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Neurological outcome in adult patients with early-treated phenylketonuria
J Pietz1, R Dunckelmann, A Rupp
1Department of Paediatric Neurology, University of Heidelberg, Germany.
Insights
Even with early treatment for phenylketonuria (PKU), adults show subtle neurological deficits like tremor and reduced fine motor skills. Lifelong monitoring is recommended for PKU patients due to potential future neurological decline.
Area of Science:
- Neurology
- Metabolic Disorders
- Neurodevelopmental Disorders
Background:
- Phenylketonuria (PKU) is a genetic disorder requiring early dietary intervention.
- Long-term neurological outcomes in treated PKU patients remain a concern.
- Subtle neurological abnormalities may persist despite early treatment.
Purpose of the Study:
- To investigate the neurological status of early-treated adult patients with phenylketonuria.
- To compare neurological outcomes with control subjects.
- To identify factors influencing neurological function in PKU.
Main Methods:
- Clinical-neurological examination
- Fine motor skills assessment
- IQ testing (WAIS-R)
- Neuropsychological attention tasks
- MRI scans (in a subset of patients)
Main Results:
- Increased tremor (28% vs 15%) and reduced fine motor abilities were observed in PKU patients.
- IQ scores were lower in PKU patients (mean 97.6) compared to controls (mean 105.5).
- Attention task performance correlated with current phenylalanine levels, unlike other parameters.
Conclusions:
- Early-initiated treatment for PKU does not entirely prevent subtle neurological deficits in adulthood.
- Neurological deterioration may occur later in life, necessitating lifelong patient monitoring.
- Continuous monitoring is advised for all phenylketonuria patients, regardless of dietary adherence.
Unlabelled:
Due to the observation of severe neurological symptoms in single patients as well as brain imaging, neuropsychological and neurophysiological abnormalities, the long-term prognosis of treated phenylketonuria is still under discussion. We investigated the neurological outcome of 57 (24 male, 33 female) patients with phenylketonuria (diet onset < 3 months) at a mean age of 23.6 (17-33) years in comparison to control subjects. Methods used were a clinical-neurological examination, tests for fine motor abilities, IQ test (WAIS-R), a neuropsychological attention task and MRI (30 patients only). Tremor was increased in the patients (28%) compared to controls (15%). Fine motor abilities were significantly reduced in three areas: hand-wrist steadiness, finger-hand dexterity and hand-wrist speed. Tremor as well as reduced fine motor skills were not associated with treatment-related variables, e.g. diet onset, strictness of biochemical control or amount of MRI white matter change. IQ was lower in patients (mean 97.6) compared to matched control subjects (mean 105.5). IQ at 12 years was correlated with biochemical control from birth up to the age of 12 and remained stable up to adult age, independent of biochemical control after 12 years of age. In contrast to the other outcome parameters, the performance in a neuropsychological attention task was influenced by the concurrent plasma phenylalanine concentration. Specific late-onset neurological impairment was not identified in this sample of early-treated adults with phenylketonuria.
Conclusion:
Careful neurological investigation revealed subtle symptoms of brain damage even after early-initiated treatment in adult patients with phenylketonuria. At present it cannot be excluded that further neurological deterioration could emerge later in life. Thus, patients with phenylketonuria - either on or off diet - should be monitored throughout life.