Zellweger spectrum disorders: clinical manifestations in patients surviving into adulthood.
BACKGROUND
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.
Department of Paediatric Neurology, Emma Children's Hospital, Academic Medical Centre (AMC), University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.|Laboratory Genetic Metabolic Diseases, Emma Children's Hospital, AMC, University of Amsterdam, Amsterdam, The Netherlands.
Kevin
K
Berendse
Department of Paediatric Neurology, Emma Children's Hospital, Academic Medical Centre (AMC), University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
Marc
M
Engelen
Laboratory Genetic Metabolic Diseases, Emma Children's Hospital, AMC, University of Amsterdam, Amsterdam, The Netherlands.
Sacha
S
Ferdinandusse
Department of Radiology, AMC, University of Amsterdam, Amsterdam, The Netherlands.
Charles B L M
CB
Majoie
Laboratory Genetic Metabolic Diseases, Emma Children's Hospital, AMC, University of Amsterdam, Amsterdam, The Netherlands.
Hans R
HR
Waterham
Laboratory Genetic Metabolic Diseases, Emma Children's Hospital, AMC, University of Amsterdam, Amsterdam, The Netherlands.
Frédéric M
FM
Vaz
Department of Neurology and Clinical Neurophysiology, AMC, University of Amsterdam, Amsterdam, The Netherlands.
Johannes H T M
JH
Koelman
Department of Paediatric Neurology, Emma Children's Hospital, Academic Medical Centre (AMC), University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
Peter G
PG
Barth
Laboratory Genetic Metabolic Diseases, Emma Children's Hospital, AMC, University of Amsterdam, Amsterdam, The Netherlands.
Ronald J A
RJ
Wanders
Department of Paediatric Neurology, Emma Children's Hospital, Academic Medical Centre (AMC), University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. B.T.PollThe@amc.uva.nl.
Bwee Tien
BT
Poll-The
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D012189:Retrospective Studies; D066127:White Matter / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult; D015211:Zellweger Syndrome / Q000378:metabolism / Q000473:pathology*
D015415:Biomarkers