Neurological manifestations in adults with phenylketonuria: new cases and review of the literature

• Published in: Journal of neurology Vol. 267; no. 2; pp. 531 - 542
• Main Authors: Jaulent, Paul, Charriere, Sybil, Feillet, François, Douillard, Claire, Fouilhoux, Alain, Thobois, Stéphane
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.02.2020; Springer Nature B.V; Springer Verlag
• Subjects: Adults; Cerebellar ataxia; Cerebellum; Diagnosis; Diet; Headache; Inborn errors of metabolism; Life Sciences; Literature reviews; Magnetic resonance imaging; Medicine; Medicine & Public Health; Neuroimaging; Neurological complications; Neurology; Neuroradiology; Neurosciences; Nutrient deficiency; Original Communication; Phenylalanine; Phenylketonuria; Reflexes; Tremor; Neurological symptoms; Brain MRI; Leucopathy; Adult phenylketonuria
• ISSN: 0340-5354; 1432-1459
• DOI: 10.1007/s00415-019-09608-2

Objective Phenylketonuria (PKU) is a rare autosomal recessive disease characterised by high plasma phenylalanine levels inducing, if untreated, serious neurological manifestations in children but also, rarely, in adults who stopped their diet. The objective of the study was to describe the neurological manifestations observed in adults with PKU. Methods We analysed cases reported in French reference centres for inborn errors of metabolism and cases already reported in the literature. Results We report 8 new cases of neurological manifestations and 22 cases in the literature, which occurred in adult PKU patients, associated with chronic or rapid increase of phenylalanine levels, mostly when strict low-phenylalanine diet was stopped early in life. Neurological symptoms consisted in cerebellar ataxia, tremor, brisk reflexes, visual loss, sensory manifestations, and/or headaches. Visual loss was more frequent in the new cases (4/8) of the present series than in the literature (4/22). These neurological complications were associated with leucopathy on brain magnetic resonance imaging (27/29). The start of a low-phenylalanine diet improved or fully reversed neurological manifestations, even in patients with late diagnosis during adulthood. Conclusion Neurological manifestations can complicate PKU in adult patients with elevated phenylalanine levels, after long or short period of diet discontinuation. Neurologists should be aware of this diagnosis, and measure phenylalaninemia in case of neurological symptoms associated with non-specific leucopathy on brain MRI. PKU patients should be systematically encouraged to continue their diet and their medical follow-up to avoid neurological complications.