Congenital disorder of glycosylation Ic in patients of Indian origin

ALG6-CDG in South Africa: Genotype-Phenotype Description of Five Novel Patients

“…The p.A333V mutation is associated with a mild to moderate phenotype which indicates that the novel frameshift mutation (c.1338dupA), which results in the formation of a truncated ALG6 protein, probably explains the severe phenotype and early death of the patient as well as the unusually low serum tetrasialotransferrin. The phenotypic variation from the typical ALG6 deficiency concurs with previous literature of rare ALG6-CDG cases with multiple organ involvement and intestinal abnormality, e.g., PLE (Westphal et al 2000b;Newell et al 2003;Al-Owain et al 2010). Patients 2, 3, 4, and 5 presented with the classical ALG6-CDG phenotype comprising of a variable degree of neurological involvement, including hypotonia and resistant epilepsy.…”

“…Patient 1 showed a severe, earlyonset, neuro-gastrointestinal presentation comparable with previously described case studies (Westphal et al 2000b;Damen et al 2004;Newell et al 2003). The patient was compound heterozygous for the prevalent c.998C>T (p.A333V) missense mutation (originally described by Imbach et al 1999) and a novel c.1338dupA (p.V447SfsX44) frameshift mutation in the ALG6 gene.…”

“…It was first reported in 1998 (Burda et al 1998;K€ orner et al 1998) and about 37 patients have been described (Imbach et al 1999Gr€ unewald et al 2000;Hanefeld et al 2000;Westphal et al 2000aWestphal et al , b, 2003de Lonlay et al 2001;Schollen et al 2002;Newell et al 2003;Sun et al 2005;Vuillaumier-Barrot 2005;Eklund et al 2006;Haeuptle and Hennet 2009;Al-Owain et al 2010). The clinical presentation is mainly characterized by feeding problems and a moderately pronounced neurological disorder with psychomotor retardation, hypotonia, epilepsy, and internal strabismus Newell et al 2003). A minority of patients show other symptoms, particularly intestinal (such as protein-losing enteropathy (PLE)) and liver involvement (Damen et al 2004).…”

“…A minority of patients show other symptoms, particularly intestinal (such as protein-losing enteropathy (PLE)) and liver involvement (Damen et al 2004). Striking biochemical features are unusually low serum cholesterol; blood coagulation factor XI and anticoagulation factors antithrombin, protein C, and protein S; as well as variable hypoalbuminemia; low serum LDL-cholesterol; and endocrinological abnormalities (K€ orner et al 1998;Gr€ unewald et al 2000;Hanefield et al 2000;Newell et al 2003;Sun et al 2005;Westphal et al 2000a, b). Table 1 summarizes clinical and molecular findings in ten ALG6-CDG patients reported since 1998.…”

“…Table 1 summarizes clinical and molecular findings in ten ALG6-CDG patients reported since 1998. Twenty-one different mutations have been described but the majority of patients have the c.998C>T (p.A333V) mutation, either in a compound heterozygous or homozygous state (Imbach et al 1999Gr€ unewald et al 2000;Hanefeld et al 2000;Westphal et al 2000aWestphal et al , b, 2003de Lonlay et al 2001;Schollen et al 2002;Newell et al 2003;Sun et al 2005;Vuillaumier-Barrot 2005;Eklund et al 2006;Haeuptle and Hennet 2009;Al-Owain et al 2010). Haeuptle and Hennet (2009) reported that most of the mutations affect amino acids positioned within the 11 TM domains, which compromise the integrity of the protein structure and alter the properties responsible for the binding of dolichol-linked glycans.…”