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Zellweger spectrum disorders: clinical manifestations in patients surviving into adulthood
Author(s) -
Berendse Kevin,
Engelen Marc,
Ferdinandusse Sacha,
Majoie Charles B. L. M.,
Waterham Hans R.,
Vaz Frédéric M.,
Koelman Johannes H. T. M.,
Barth Peter G.,
Wanders Ronald J. A.,
PollThe Bwee Tien
Publication year - 2016
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-015-9880-2
Subject(s) - medicine , natural history , young adult , disease , pediatrics , age of onset , cohort , peroxisomal disorder , pathology , peroxisome , receptor
We describe the natural history of patients with a Zellweger spectrum disorder (ZSD) surviving into adulthood. Methods Retrospective cohort study in patients with a genetically confirmed ZSD. Results All patients ( n = 19; aged 16–35 years) had a follow‐up period of 1–24.4 years (mean 16 years). Seven patients had a progressive disease course, while 12 remained clinically stable during follow‐up. Disease progression usually manifests in adolescence as a gait disorder, caused by central and/or peripheral nervous system involvement. Nine were capable of living a partly independent life with supported employment. Systematic MRI review revealed T2 hyperintense white matter abnormalities in the hilus of the dentate nucleus and/or peridentate region in nine out of 16 patients. Biochemical analyses in blood showed abnormal peroxisomal biomarkers in all patients in infancy and childhood, whereas in adolescence/adulthood we observed normalization of some metabolites. Conclusions The patients described here represent a distinct subgroup within the ZSDs who survive into adulthood. Most remain stable over many years. Disease progression may occur and is mainly due to cerebral and cerebellar white matter abnormalities, and peripheral neuropathy.