Abstract
Congenital disorders of glycosylation (CDG) are an expanding group of inherited metabolic diseases with multisystem involvement. ALG6-CDG (CDGIc) is an endoplasmatic reticulum defect in N-glycan assembly. It is usually milder than PMM2-CDG (CDG-Ia) and so is its natural course. It is characterized by psychomotor retardation, seizures, ataxia, and hypotonia. In contrast to PMM2-CDG (CDGIa), there is no cerebellar hypoplasia. Cardiomyopathy has been reported in a few CDG types and in a number of patients with unexplained CDG. We report an 11 year old Saudi boy with severe psychomotor retardation, seizures, strabismus, inverted nipples, dilated cardiomyopathy, and a type 1 pattern of serum transferrin isoelectrofocusing. Phosphomannomutase and phosphomannose isomerase activities were normal in fibroblasts. Full gene sequencing of the ALG6 gene revealed a novel mutation namely c.482A>G (p.Y161C) and heterozygosity in the parents. This report highlights the importance to consider CDG in the differential diagnosis of unexplained cardiomyopathy.
Highlights
Inborn errors of metabolism (IEM) account for only 5% of all pediatric cardiomyopathy and 15% of patients with known causes
Cardiomyopathy has been reported in PMM2-Congenital disorders of glycosylation (CDG) (The novel CDG nomenclature is used ie the non-italicized gene symbol followed by: CDG [2,3]), ALG12-CDG (CDG-Ig), DK1-CDG (CDGIm) and COG7-CDG (CDG-IIe), as well as in patients with an unexplained CDG
The method of choice for screening of these disorders is still isoelectrofocusing of serum transferrins (IEF) [8]
Summary
Inborn errors of metabolism (IEM) account for only 5% of all pediatric cardiomyopathy and 15% of patients with known causes. ALG6-CDG (MIM #603147) is caused by defects in the ALG6 gene coding for Dol-P-Glc:Man9-GlcNAc2-P-PDol glucosyltransferase (glucosyltransferase 1) It is as a rule milder than PMM2-CDG (CDGIa) and is characterized by psychomotor retardation, axial hypotonia, seizures, ataxia, strabismus, feeding difficulties and a very low serum cholesterol and clotting factor XI [11,12,13,14]. On physical examination at the age of 7 years, the child was wheelchair bound with severe mental retardation and no speech His head circumference and weight were on the 50 centile. The family history revealed that the patient was the fourth child born to healthy consanguineous parents, and he had two healthy siblings His elder sister died at 7 years of age with a similar but more severe syndrome comprising microcephaly, deafness, blindness, severe psychomotor retardation and intractable seizures. She was investigated thoroughly for metabolic disorders including mitochondrial disorders and chromosomal abnormalities; no diagnosis was made at that time
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