Neurological Presentation in Pediatric Patients with Congenital Disorders of Glycosylation Type Ia[*]

Abstract

Objective

Congenital disorders of glycosylation (CDG), formerly called carbohydrate-deficient glycoprotein syndromes, constitute a newly identified group of multisystem disorders characterized by defective glycosylation of N-glycosylated proteins. The objective of this work was to describe precisely neurological findings in patients with type Ia CDG (CDG-Ia) and to compare our results with the literature.

Study Design

We retrospectively reviewed neurological and neurodevelopmental, neuroimaging, and genetic features in ten patients with CDG-Ia who mainly presented with neurological abnormalities during childhood and therefore were referred to a neuropediatrician or a neurogeneticist.

Results

Neurological manifestations had a static clinical course, dominated by mental retardation and cerebellar dysfunction, and acute episodes: stroke-like episodes and seizures. However, microcephaly, retinopathy, and polyneuropathy were progressive. All patients had severe global neurodevelopmental delay: only one was able to walk alone at ten years of age and only one could read. Marked heterogeneity in manifestations and delay of diagnosis was noted across the patients. Cerebellar hypoplasia was found by magnetic resonance imaging in all ten patients and olivopontocerebellar hypoplasia in four patients. As in the literature, there was no clear phenotype-mutation correlation.

Conclusion

Our findings confirm the importance of a precise and complete description of the neurological and neuroradiological phenotype delineating the phenotype of CDG-Ia to increase the likelihood of diagnosing the disease.

Key words

Congenital disorders of glycosylation Type Ia - mental retardation - ataxia - cerebellar atrophy - olivopontocerebellar atrophy

1 E. M.C. and Y. M. contributed equally to this paper.

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1 E. M.C. and Y. M. contributed equally to this paper.