Congenital Disorder of Glycosylation Type Ia (Jaeken Syndrome): A Case Report

Background. Congenital disorder of glycosylation type Ia (Jaeken syndrome; congenital disorder of glycosylation, type Ia; CDG-Ia) is a hereditary progressive disorder with a pronounced neurodegenerative component, caused by pathogenic variants in the PMM2 gene (encoding the enzyme phosphomannomutase-2). CDG-Ia accounts for the majority of registered patients with congenital disorders of glycosylation (62% in 2018). At least 1,000 patients with CDG caused by PMM2 gene mutations are known, but due to diagnostic difficulties, the true number of individuals with this condition is undoubtedly much higher.

Case Report. We present a case report of CDG-Ia in a child with progressive ataxia, nystagmus, and delayed psycho-speech and motor development. The patient was a female infant, born from the third pregnancy, which was complicated by acute enteritis at 15 weeks of gestation and an acute respiratory viral infection at 20 weeks of gestation. Delivery was at term (42 weeks) and was the second childbirth. The child was born into a family with no history of hereditary disorders; the parents were 37 and 38 years old at the time of the girl’s birth. The disease manifested from birth with reduced sucking reflex, breast refusal, and slow weight gain. At 1.5 months of age, horizontal nystagmus was added to these symptoms. The diagnosis was established based on molecular genetic testing of the proband using next-generation sequencing to rule out hereditary ataxias, as well as transferrin isoelectric focusing (revealing an abnormal transferrin spectrum: abnormal diand asialotransferrins — isoforms S2 and S0), and magnetic resonance imaging of the brain (showing progressive cerebellar atrophy at 11 months of age).

Conclusion. We describe a case report of CDG-Ia in a child from a family in which both parents are carriers of mutant alleles and have a healthy child. Despite comprehensive patient management, progressive disease course was observed; the girl has severe psychomotor retardation and clinical signs of multisystem involvement of internal organs. Arresting disease progression is not feasible due to the underlying genetic defect in the synthesis of mannose and glycoproteins, which are essential components of most metabolic pathways in the body.

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