ALG1-CDG: A new case with early fatal outcome

•A new patient with congenital disorder of glycosylation type Ik (ALG1-CDG).•The boy had a severe multiorgan involvement with death in early infancy.•Compound heterozygosity was found for c.1145 T > C (M382T) and c.1312C > T (R438W).•Previously reported speculation on R438W as a frequent polymorphism can be disproved.•We confirmed both of the mutations as disease-causing for ALG1-CDG (CDG-Ik).

Congenital disorders of glycosylation (CDG) are a growing group of inherited metabolic disorders where enzymatic defects in the formation or processing of glycolipids and/or glycoproteins lead to variety of different diseases.The deficiency of GDP-Man:GlcNAc2-PP-dolichol mannosyltransferase, encoded by the human ortholog of ALG1 from yeast, is known as ALG1-CDG (CDG-Ik). The phenotypical, molecular and biochemical analysis of a severely affected ALG1-CDG patient is the focus of this paper. The patient's main symptoms were feeding problems and diarrhea, profound hypoproteinemia with massive ascites, muscular hypertonia, seizures refractory to treatment, recurrent episodes of apnoea, cardiac and hepatic involvement and coagulation anomalies.Compound heterozygosity for the mutations c.1145 T > C (M382T) and c.1312C > T (R438W) was detected in the patient's ALG1-coding sequence. In contrast to a previously reported speculation on R438W we confirmed both mutations as disease-causing in ALG1-CDG.