A novel mutation and first report of dilated cardiomyopathy in ALG6-CDG (CDG-Ic): a case report.
Congenital disorders of glycosylation (CDG) are an expanding group of inherited metabolic diseases with multisystem involvement. ALG6-CDG (CDGIc) is an endoplasmatic reticulum defect in N-glycan assembly. It is usually milder than PMM2-CDG (CDG-Ia) and so is its natural course. It is characterized by psychomotor retardation, seizures, ataxia, and hypotonia. In contrast to PMM2-CDG (CDGIa), there is no cerebellar hypoplasia. Cardiomyopathy has been reported in a few CDG types and in a number of patients with unexplained CDG. We report an 11 year old Saudi boy with severe psychomotor retardation, seizures, strabismus, inverted nipples, dilated cardiomyopathy, and a type 1 pattern of serum transferrin isoelectrofocusing. Phosphomannomutase and phosphomannose isomerase activities were normal in fibroblasts. Full gene sequencing of the ALG6 gene revealed a novel mutation namely c.482A>G (p.Y161C) and heterozygosity in the parents. This report highlights the importance to consider CDG in the differential diagnosis of unexplained cardiomyopathy.
Al-Owain
Mohammed
M
Department of Medical Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. alowain@kfshrc.edu.sa
Mohamed
Sarar
S
Kaya
Namik
N
Zagal
Ahmad
A
Matthijs
Gert
G
Jaeken
Jaak
J
D002311:Cardiomyopathy, Dilated / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics*; D002648:Child; D018981:Congenital Disorders of Glycosylation / Q000235:genetics*; D005964:Glucosyltransferases / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation
D008565:Membrane Proteins; C498467:ALG6 protein, human; D005964:Glucosyltransferases
Hum Mol Genet. 2001 Mar 15;10(6):591-7
11230178
J Inherit Metab Dis. 2008 Dec;31(6):669-72
18949576
Ultrastruct Pathol. 2007 May-Jun;31(3):189-97
17613998
Fetal Diagn Ther. 2009;25(1):54-7
19176971
Pediatr Res. 2002 Nov;52(5):618-24
12409504
Prog Pediatr Cardiol. 2007;24(1):15-25
19030119
J Inherit Metab Dis. 2009 Dec;32 Suppl 1:S313-9
19757145
Neuropediatrics. 2000 Apr;31(2):60-2
10832578
Hum Genet. 2000 May;106(5):538-45
10914684
Cardiol Young. 2003 Aug;13(4):345-51
14694955
J Inherit Metab Dis. 2008 Apr;31(2):267-9
18392739
Curr Opin Neurol. 2001 Dec;14(6):811-5
11723393
Am J Hum Genet. 2007 Mar;80(3):433-40
17273964
Genome Res. 2003 Sep;13(9):2129-41
12952881
Nat Med. 2004 May;10(5):518-23
15107842
Am J Med Genet A. 2007 Jun 15;143A(12):1371-8
17506107
Hum Pathol. 2007 Nov;38(11):1714-9
17954208
Biochim Biophys Acta. 2009 Sep;1792(9):825-6
19765534
Nucleic Acids Res. 2003 Jul 1;31(13):3812-4
12824425
Am J Med Genet A. 2005 Aug 15;137(1):22-6
16007612
Acta Neuropathol. 2005 Apr;109(4):433-42
15714316
Arch Dis Child. 1995 May;72(5):445-6
7618917
Ann Neurol. 2000 Jun;47(6):776-81
10852543
J Inherit Metab Dis. 2000 Jun;23(4):391-5
10896302
Mol Genet Metab. 2000 Jul;70(3):219-23
10924277
Arch Dis Child. 1991 Sep;66(9):1027-32
1929507
J Inherit Metab Dis. 2003;26(2-3):99-118
12889654
Clin Chim Acta. 1984 Dec 29;144(2-3):245-7
6543331
J Inherit Metab Dis. 1996;19(2):257-9
8739980
Br J Ophthalmol. 2006 Jan;90(1):115-6
16361681
J Inherit Metab Dis. 2000 Mar;23(2):162-74
10801058
J Inherit Metab Dis. 1992;15(6):857-61
1293380