Mucolipidosis II / IIIA (GNPTAB)
Mucolipidosis II and mucolipidosis IIIA are pan-ethnic autosomal recessive diseases caused by pathogenic variants in the gene GNPTAB. Mucolipidosis II: Patients are typically affected at birth, with limited postnatal growth, abnormalities of the joints, skeletal malformations, and thickening of cardiac valves and airways. Most will also experience impaired cognitive development, and are never able to walk unassisted or speak sentences. Life expectancy is in early childhood. Mucolipidosis IIIA: This disorder causes progressive stiffening and pain in joints, skeletal malformations, and thickening of cardiac valves and airways. Some patients may have impaired motor development, but typically all mental milestones are met on time. Patients are usually not affected until the age of three and may survive into early/middle adulthood. Individuals with two null alleles are more likely to be diagnosed with mucolipidosis II, whereas patients with missense and splice site variants are more likely to be diagnosed with mucolipidosis IIIA. However, some patients have a clinical phenotype that overlaps both forms of mucolipidosis, and it may be difficult to predict this phenotype based on the inherited variants.
For information about carrier frequency and residual risk, please see the residual risk table.