Paul Jaulent1, Sybil Charriere2,3,4,5,6, François Feillet7, Claire Douillard8, Alain Fouilhoux9, Stéphane Thobois1,10,11. 1. Hospices Civils de Lyon, Hôpital Neurologique Pierre Wertheimer, Neurologie C, 69677, Bron Cedex, France. 2. Hospices Civils de Lyon, Hôpital Cardiovasculaire Louis Pradel, Fédération D'endocrinologie, Maladies métaboliques, diabète Et Nutrition, Groupement Hospitalier Est, 28 avenue Doyen Lépine, 69677, Bron Cedex, France. sybil.charriere@chu-lyon.fr. 3. INSERM U1060, Laboratoire Carmen, Université Lyon 1, INRA U1235, INSA de Lyon, 69621, Villeurbanne, France. sybil.charriere@chu-lyon.fr. 4. CENS, Centre de Recherche en Nutrition Humaine Rhône Alpes, 69921, Oullins Cedex, France. sybil.charriere@chu-lyon.fr. 5. Université Lyon 1 Claude Bernard, Faculté de médecine Lyon EST, 69373, Lyon, France. sybil.charriere@chu-lyon.fr. 6. Hospices Civils de Lyon, Centre de référence Des Maladies héréditaires du métabolisme de Lyon, Groupement Hospitalier Est, 69677, Bron Cedex, France. sybil.charriere@chu-lyon.fr. 7. CHU de Nancy, Hôpitaux de Brabois, Centre de référence Des Maladies héréditaires du métabolisme de Nancy, 54511, Vandoeuvre-les Nancy, France. 8. Centre Hospitalier Régional Universitaire de Lille, Hopital Claude Huriez, Service D'Endocrinologie-Diabétologie-Métabolisme, Hopital Huriez, 59037, Lille, France. 9. Hospices Civils de Lyon, Centre de référence Des Maladies héréditaires du métabolisme de Lyon, Groupement Hospitalier Est, 69677, Bron Cedex, France. 10. Université Lyon 1 Claude Bernard, Faculté de médecine Lyon EST, 69373, Lyon, France. 11. CNRS, Institut Des Sciences Cognitives Marc Jeannerod, UMR 5229, 69675, Bron, France.
Abstract
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.
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.
Authors: Nasser A Elhawary; Imad A AlJahdali; Iman S Abumansour; Ezzeldin N Elhawary; Nagwa Gaboon; Mohammed Dandini; Abdulelah Madkhali; Wafaa Alosaimi; Abdulmajeed Alzahrani; Fawzia Aljohani; Ehab M Melibary; Osama A Kensara Journal: Hum Genomics Date: 2022-07-19 Impact factor: 6.481