title: CDG-IL: an infant with a novel mutation in the ALG9 gene and additional phenotypic features.
abstract: We describe the second case of congenital disorder of glycosylation type IL (CDG-IL) caused by deficiency of the ALG9 a1,2 mannosyltransferase enzyme. The female infant's features included psychomotor retardation, seizures, hypotonia, diffuse brain atrophy with delayed myelination, failure to thrive, pericardial effusion, cystic renal disease, hepatosplenomegaly, esotropia, and inverted nipples. Lipodystrophy and dysmorphic facial features were absent. Magnetic resonance imaging of the brain showed volume loss in the cerebral hemispheres and cerebellum and delayed myelination. Laboratory investigations revealed low levels of multiple serum proteins including antithrombin III, factor XI, and cholesterol. Hypoglycosylation was confirmed by the typical CDG type 1 pattern of serum transferrin analyzed by isoelectric focusing. A defect in the ALG9 enzyme was suggested by the accumulation of the DolPP-GlcNAc2Man6 and DolPP-GlcNAc2Man8 in the patient's fibroblasts and confirmed by mutation analysis: the patient is homozygous for the ALG9 mutation p.Y286C. The causal effect of the mutation was shown by complementation assays in alg9 deficient yeast cells. The child described here further delineates the clinical spectrum of CDG-IL and confirms the significant clinical overlap amongst CDG subtypes.
authors.affiliation: Hospital for Sick Children, Pediatrics, Toronto, Ontario, Canada. michael.weinstein@sickkids.ca
authors.forename: Michael
authors.initials: M
authors.lastname: Weinstein
authors.forename: Els
authors.initials: E
authors.lastname: Schollen
authors.forename: Gert
authors.initials: G
authors.lastname: Matthijs
authors.forename: Christine
authors.initials: C
authors.lastname: Neupert
authors.forename: Thierry
authors.initials: T
authors.lastname: Hennet
authors.forename: Claudia E
authors.initials: CE
authors.lastname: Grubenmann
authors.forename: Christian G
authors.initials: CG
authors.lastname: Frank
authors.forename: Markus
authors.initials: M
authors.lastname: Aebi
authors.forename: Joe T R
authors.initials: JT
authors.lastname: Clarke
authors.forename: Anne
authors.initials: A
authors.lastname: Griffiths
authors.forename: Lorne
authors.initials: L
authors.lastname: Seargeant
authors.forename: Nicola
authors.initials: N
authors.lastname: Poplawski
mesh_terms: D043402:Cathepsin A / Q000378:metabolism; D018981:Congenital Disorders of Glycosylation / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D005260:Female; D005816:Genetic Complementation Test; D006031:Glycosylation; D006801:Humans; D007223:Infant; D008364:Mannosyltransferases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D009123:Muscle Hypotonia / Q000473:pathology; D009154:Mutation; D010641:Phenotype; D011596:Psychomotor Disorders / Q000473:pathology; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development; D012640:Seizures / Q000473:pathology
chemical_list: D008364:Mannosyltransferases; D043402:Cathepsin A