title: Dolichol kinase deficiency (DOLK-CDG) with a purely neurological presentation caused by a novel mutation.
abstract: A 4-month old boy presented with multiple epileptic seizure types including West syndrome. Screening for infectious and structural etiologies showed normal results. A metabolic investigation was undertaken to investigate the cause of his neurological disease. Screening for congenital disorders of glycosylation (CDG) by HPLC analysis of serum carbohydrate-deficient transferrin (CDT) showed a type 1 pattern with 18% disialotransferrin (reference < 2%) and 2% asialotransferrin (reference 0). An undiagnosed 10-year old sister with a similar clinical history with infantile spasms at age 4 months, intellectual disability and an autism spectrum disorder, also showed a type 1 CDT pattern. Both siblings lacked dysmorphic features and extra-cerebral symptoms. The boy had cytotoxic edema of the thalamus and mesencephalon on MRI at age 7 months, whereas the girl had normal MRI at age 8 months. Phosphomannomutase (PMM) and phosphomannose isomerase (MPI) activities in cultured fibroblasts were normal, excluding PMM2-CDG and MPI-CDG. Fibroblast lipid-linked oligosaccharide analysis was also normal, suggesting an early defect in glycan assembly. Sequence analysis of the dolichol kinase gene revealed a homozygous new missense mutation (p.M1?; c.2 T > C) in both siblings. In conclusion, two siblings were demonstrated to suffer from DOLK-CDG (MIM 610768) and to be homozygous for a new mutation. They presented with West syndrome and so far show a purely neurological phenotype.
authors.affiliation: Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; Karolinska University Laboratory, Stockholm, Sweden. Electronic address: anders.helander@ki.se.
authors.forename: Anders
authors.initials: A
authors.lastname: Helander
authors.forename: Tommy
authors.initials: T
authors.lastname: Stödberg
authors.forename: Jaak
authors.initials: J
authors.lastname: Jaeken
authors.forename: Gert
authors.initials: G
authors.lastname: Matthijs
authors.forename: Maud
authors.initials: M
authors.lastname: Eriksson
authors.forename: Gösta
authors.initials: G
authors.lastname: Eggertsen
mesh_terms: D000293:Adolescent; D002648:Child; D018981:Congenital Disorders of Glycosylation / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D005838:Genotype; D006031:Glycosylation; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000172:deficiency* / Q000235:genetics; D035781:Siblings; D014168:Transferrin / Q000378:metabolism
chemical_list: D014168:Transferrin; D017853:Phosphotransferases (Alcohol Group Acceptor); C020087:dolichol kinase
keywords: Carbohydrate-deficient transferrin; Congenital disorder of glycosylation; DOLK-CDG; Dolichol kinase; Transferrin glycosylation