A number sign (#) is used with this entry because of evidence that autosomal recessive congenital disorder of glycosylation type Iw (CDG1WAR) is caused by homozygous mutation in the STT3A gene (601134) on chromosome 11q24.

Shrimal et al. (2013) reported 2 sibs, born of consanguineous Pakistani parents, with autosomal recessive congenital disorder of glycosylation. The patients had delayed psychomotor development with impaired intellectual development, microcephaly, failure to thrive, seizures, hypotonia, and cerebellar atrophy. At age 13 years, 1 was more severely delayed, with inability to sit, poor visual tracking, and intractable seizures. Serum transferrin studies showed abnormal glycosylation consistent with a type I pattern.

Ghosh et al. (2017) reported 5 affected individuals, ranging in age from 6 to 28 years, from a multiply consanguineous Pakistani family segregating congenital disorder of glycosylation type I. All 5 individuals had a homozygous mutation in the STT3A gene and all had developmental delay, impaired intellectual development, and seizures. Two individuals (IV-1 and IV-2), who also had deletions involving the TUSC3 gene in heterozygous (IV-2) or homozygous (IV-1) state, had optic atrophy and episodes of reduced consciousness and hypothermia that was suggestive of hypothalamic dysfunction. Patient IV-1 had a more severe clinical neurodevelopmental course compared to the other affected family members. Feeding problems requiring gastrostomy tube insertion was reported in 3 individuals (IV-1, IV-2, III-7), one of whom (IV-1) also had failure to thrive. Two individuals (III-7 and III-8) had sleep disturbances, 3 (III-7, III-8, and III-9) had stereotypic behaviors, and 1 (III-9) had self-injurious behaviors. A 1-month-old family member (IV-4) with an STT3A mutation was asymptomatic at the time of evaluation.

The transmission pattern of type I congenital disorder of glycosylation in the family reported by Shrimal et al. (2013) was consistent with autosomal recessive inheritance.

In 2 sibs, born of consanguineous Pakistani parents, with autosomal recessive congenital disorder of glycosylation type Iw, Shrimal et al. (2013) identified a homozygous missense mutation in the STT3A gene (V626A; 601134.0001). The mutation was found by homozygosity mapping and candidate gene sequencing. Patient cells showed reduced amounts of the STT3A protein. Patient cells also showed incomplete N-glycosylation of a GFP biomarker that was complemented by wildtype STT3A, as well as lower glycosylation of the STT3A substrates prosaposin (PSAP; 176801) and granulin (GRN; 138945) compared to control cells.

Ghosh et al. (2017) identified homozygosity for the V626A mutation in the STT3A gene in 5 individuals from a multiply consanguineous Pakistani family with CDG1WAR. The mutation was identified by autozygosity mapping and whole-exome sequencing and was confirmed by Sanger sequencing in all affected individuals. Two of those affected were also homozygous (patient IV-1) or heterozygous (patient IV-2) for a partial deletion of the TUSC3 gene (601385); patient IV-1 had a more severe neurodevelopmental clinical course compared to other affected family members, whereas patient IV-2 had a similar phenotype to family members with only the STT3A mutation.