Screening for CDG type Ia in Joubert syndrome.
BACKGROUND
The features of Joubert syndrome include hypotonia, ataxia, characteristic neuro-imaging findings, episodic hypoventilation, psychomotor retardation, and abnormal eye movements. Common symptoms in congenital disorders of glycosylation (CDG) type Ia are muscle hypotonia, cerebellar hypoplasia, ataxia, mental retardation, ophthalmologic involvement, failure to thrive, abnormal fat distribution, and hepatopathy. It has been postulated that some Joubert syndrome patients might have an underlying disorder of protein glycosylation.


METHODS
Screening for disorders of glycosylation was performed in five children diagnosed with Joubert syndrome. Data were retrospectively collected from clinical charts, the patients were reexamined by clinical geneticists, and available neuro-imaging data were also reanalyzed. Diagnoses were established based on results of serum transferrin isoelectric focusing, phosphomannomutase enzyme activity measurements, and DNA mutation analysis.


RESULTS
We confirmed the diagnoses of CDG type Ia in two of the five children originally diagnosed with Joubert syndrome. The symptoms of the two syndromes were clearly distinguishable.


CONCLUSIONS
Syndromic patients with congenital vermis malformations should be screened for congenital disorders of glycosylation.
Department of Pediatrics, University Medical Center Nijmegen, Nijmegen, The Netherlands. e.morava@cukz.umcn.nl
Eva
E
Morava
Beatrix
B
Cser
Judit
J
Kárteszi
Karin
K
Huijben
Laszlo
L
Szonyi
Gyorgy
G
Kosztolanyi
Ron
R
Wevers
D000015:Abnormalities, Multiple / Q000209:etiology; D002524:Cerebellar Ataxia / Q000209:etiology; D002531:Cerebellum / Q000002:abnormalities* / Q000000981:diagnostic imaging; D002648:Child; D002675:Child, Preschool; D018981:Congenital Disorders of Glycosylation / Q000150:complications* / Q000175:diagnosis; D006031:Glycosylation; D006801:Humans; D008099:Liver / Q000473:pathology*; D008359:Mannose-6-Phosphate Isomerase / Q000032:analysis / Q000097:blood; D009123:Muscle Hypotonia / Q000209:etiology; D009154:Mutation / Q000235:genetics*; D015835:Ocular Motility Disorders / Q000209:etiology; D017875:Phosphotransferases (Phosphomutases) / Q000032:analysis / Q000097:blood; D011859:Radiography
D008359:Mannose-6-Phosphate Isomerase; D017875:Phosphotransferases (Phosphomutases); C052799:phosphomannomutase