J Med Genet 2001;38:14-19 ( January )

A broad spectrum of clinical presentations in congenital disorders of glycosylation I: a series of 26 cases

P de Lonlay^a, N Seta^b, S Barrot^b, B Chabrol^c, V Drouin^d, B M Gabriel^e, H Journel^f, M Kretz^g, J Laurent^a, M Le Merrer^h, A Leroyⁱ, D Pedespan^j, P Sarda^k, N Villeneuve^l, J Schmitz^a, E van Schaftingen^m, G Matthijs^m, J Jaeken^m, C Kornerⁿ, A Munnich^h, J M Saudubray^a, V Cormier-Daire^h

^a Département de Pédiatrie, Hôpital des Enfants-Malades, Paris, France, ^b Service de Biochimie, Hôpital Bichat, France, ^c Département de Pédiatrie, Marseille, ^d Département de Génétique, Rouen, ^e Service de Néonatologie, Avignon, ^f Département de Génétique, Vannes, France, ^g Service de Pédiatrie, Colmar, France, ^h Département de Génétique, Hôpital Necker-Enfants- Malades, 149 rue de Sèvres, 75743 Paris Cedex 15, France, ⁱ Service de Pédiatrie, Compiègne, France, ^j Service de Pédiatrie, Bordeaux, France, ^k Département de Génétique, Montpellier, France, ^l Service de Neurologie, Hôpital Saint-Vincent de Paul, Paris, France, ^m University Hospital Gasthuisberg, Leuven, Belgium, ⁿ Georg-August University, Göttingen, Germany

Correspondence to: Dr Cormier-Daire, cormier{at}necker.fr

Revised version received 3 August 2000; Accepted for publication 13 October 2000

INTRODUCTIONCongenital disorders of glycosylation (CDG), or carbohydrate deficient glycoprotein syndromes, form a new group of multisystem disorders characterised by defective glycoprotein biosynthesis, ascribed to various biochemical mechanisms.
METHODSWe report the clinical, biological, and molecular analysis of 26 CDG I patients, including 20 CDG Ia, two CDG Ib, one CDG Ic, and three CDG Ix, detected by western blotting and isoelectric focusing of serum transferrin.
RESULTSBased on the clinical features, CDG Ia could be split into two subtypes: a neurological form with psychomotor retardation, strabismus, cerebellar hypoplasia, and retinitis pigmentosa (n=11), and a multivisceral form with neurological and extraneurological manifestations including liver, cardiac, renal, or gastrointestinal involvement (n=9). Interestingly, dysmorphic features, inverted nipples, cerebellar hypoplasia, and abnormal subcutaneous fat distribution were not consistently observed in CDG Ia. By contrast, the two CDG Ib patients had severe liver disease, enteropathy, and hyperinsulinaemic hypoglycaemia but no neurological involvement. Finally, the CDG Ic patient and one of the CDG Ix patients had psychomotor retardation and seizures. The other CDG Ix patients had severe proximal tubulopathy, bilateral cataract, and white matter abnormalities (one patient), or multiorgan failure and multiple birth defects (one patient).
CONCLUSIONSOwing to the remarkable clinical variability of CDG, this novel disease probably remains largely underdiagnosed. The successful treatment of CDG Ib patients with oral mannose emphasises the paramount importance of early diagnosis of PMI deficiency.


Keywords: CDG; phosphomannomutase; phosphomannose isomerase; dolichyl-phosphate glucose:mannose 9 N-acetylglycosamine 2 glucosyltransferase

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© 2001 by J Med Genet
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