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.1145T>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.
Keywords: ALG1; ALG1 pseudogenes; ALT; AST; AT-III; Alanine-aminotransferase; Antithrombin-III; Asparagine-linked glycosylation 1 homolog (yeast, beta-1,4-mannosyltransferase)=chitobiosyldiphosphodolichol beta-mannosyltransferase; Aspartate aminotransferase; C-reactive protein (reacting with C-polysaccharide of Pneumococcus); CDG; CDT; CEPH; CHE; CK; CK-MB; CPAP; CRP; Carbohydrate deficient transferrin; Centre d'Etude du Polymorphisme Humain; Cholinesterase; Congenital disorder of glycosylation type Ik; Congenital disorders of glycosylation; Continuous positive airway pressure; Creatine kinase; Creatine kinase - muscle-brain, i.e. myocardial subtype of CK; DMEM; DMSO; DNA complementary to RNA; DPAGT1; Demethylsulfoxide; Deoxyribonucleoside triphosphate; Dolichyl-phosphate (UDP-N-acetylglucosamine) N-acetylglucosaminephosphotransferase 1; Dulbecco's Modified Eagle's Medium; EDTA; Ethylenediaminetetraacetic acid; GDP; GLDH; GOT; GPT; Glc; GlcNAc; Glucose; Glutamate dehydrogenase; Glutamic oxaloacetic transaminase; Glutamic-pyruvic transaminase; Guanosine diphosphate; HMT1; HPLC; High performance liquid chromatography; Human mannosyltransferase 1; Hypoglycosylation; Hypoproteinemia; IEF; IGF1; IGFBP3; IMPP; IgG; Immunoglobulin G; Immunoprecipitation; Insulin-like growth factor 1; Insulin-like growth factor-binding protein 3; Isoelectric focusing; Kilodaltons; LLO; Lipid-linked oligosaccharides; MEM; Man; Mannose; Minimum essential medium; N-acetyl-d-glucosamine; PAGE; PBS; PCR; PP; Phosphate buffered saline; Polyacrylamide-gel electrophoresis; Polymerase chain reaction; Pyrophosphate; RER; Rough endoplasmic reticulum; SDS; Seizures; Sodium dodecyl sulfate; cDNA; dNTP; kDa.
© 2013.