Congenital disorder of glycosylation, type IIaa is a multisystem condition that primarily affects the liver, musculoskeletal structure, and other organ systems. It is caused by pathogenic variants in the STX5 gene, which is important for proper glycosylation processes in the body. The disorder typically presents in infancy as affected individuals show signs of hepatic dysfunction and other systemic abnormalities, although precise prevalence estimates are not well established. With a complex clinical picture and an autosomal recessive inheritance pattern, the condition requires careful evaluation and ongoing management.

The clinical features of this condition are striking and involve multiple organ systems. Nearly all affected individuals have prominent liver issues, with cholestasis, hepatic failure, elevated levels of liver enzymes, hyperammonemia, and hypercholesterolemia being consistently observed. In addition, there is hypotonia, hepatomegaly, and metabolic disturbances such as hypoglycemia. Skeletal findings, including a narrow chest, shortened long bones, and knee flexion contractures, are also common. Other features that may occur in a subset of patients include cardiac anomalies like ventricular septal defects and patent ductus arteriosus, renal anomalies such as unilateral renal agenesis and hydronephrosis, and musculoskeletal abnormalities like bilateral talipes equinovarus. Not all individuals experience all features, and severity varies considerably.

This disorder results from pathogenic variants in the STX5 gene. STX5 plays a crucial role in the glycosylation process, an essential biochemical pathway for proper cellular function. The condition is inherited in an autosomal recessive pattern, meaning that an affected individual must inherit two copies of the altered gene, one from each parent. Families are encouraged to seek genetic counseling to understand recurrence risks and to discuss options for family planning. Associated genes include STX5.