Congenital Disorder of Glycosylation, Type Ia (PMM2)
Congenital disorder of glycosylation, type Ia is an autosomal recessive syndrome caused by pathogenic variants in the gene PMM2. While patients have been reported from multiple ethnicities, this disease is more common in the Ashkenazi Jewish and Caucasian populations. This disease may present in infancy, childhood or adolescence, and the clinical manifestations are highly variable. In infants, the disease may present as failure to thrive as a result of feeding problems; later, the disease may manifest as encephalopathy, hypotonia, delayed language and motor development, intellectual disability, stroke-like episodes, and retinitis pigmentosa. Severely affected individuals may die in early childhood, but more mildly affected individuals may survive into adulthood with variable intellectual disability, spinal abnormalities, endocrine dysfunction and coagulopathy. Several specific variants have been associated with milder or more severe disease, and therefore the disease severity may be predicted in some patients.
For information about carrier frequency and residual risk, please see the residual risk table.