A novel mutation and first report of dilated cardiomyopathy in ALG6-CDG (CDG-Ic): a case report

Inborn errors of metabolism (IEM) account for only 5% of all pediatric cardiomyopathy and 15% of patients with known causes. More than 40 different IEM involving cardiomyopathy exist, including energetic diseases with fatty acid oxidation defects and mitochondrial respiratory chain defects, organic acidurias, glycogen storage diseases, lysosomal storage disorders and congenital disorders of glycosylation [1]. Cardiomyopathy has been reported in PMM2-CDG (The novel CDG nomenclature is used ie the non-italicized gene symbol followed by: -CDG [2,3]), ALG12-CDG (CDG-Ig), DK1-CDG (CDG-Im) and COG7-CDG (CDG-IIe), as well as in patients with an unexplained CDG. Both hypertrophic and dilated cardiomyopathies have been described in CDG, with no common pattern observed in a particular CDG [4].Congenital disorders of glycosylation (CDG) are a rapidly growing group of inherited metabolic disorders due to defects in the synthesis of glycans and their attachment to proteins and lipids [5]. They show a broad range of clinical manifestations and may be highly variable within the same subtype and even among affected siblings [6,7]. The method of choice for screening of these disorders is still isoelectrofocusing of serum transferrins (IEF) [8]. The N-glycosylation defects can be divided in two groups: CDG-I caused by dysfunction of glycan assembly, and CDG-II, caused by abnormal glycan processing [9,10]. CDG-I patients usually show a type 1 serum transferrin IEF pattern, and CDG-II patients a type 2 pattern.ALG6-CDG (MIM #603147) is caused by defects in the ALG6 gene coding for Dol-P-Glc:Man9-GlcNAc2-P-P-Dol 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 [11-14]. Other reported features include retinal degeneration [10], deep vein thrombosis, and pseudotumor cerebri [15]