CDG-IL: an infant with a novel mutation in the ALG9 gene and additional phenotypic features.
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.
Weinstein
Michael
M
Hospital for Sick Children, Pediatrics, Toronto, Ontario, Canada. michael.weinstein@sickkids.ca
Schollen
Els
E
Matthijs
Gert
G
Neupert
Christine
C
Hennet
Thierry
T
Grubenmann
Claudia E
CE
Frank
Christian G
CG
Aebi
Markus
M
Clarke
Joe T R
JT
Griffiths
Anne
A
Seargeant
Lorne
L
Poplawski
Nicola
N
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
D008364:Mannosyltransferases; D043402:Cathepsin A