Nacetylgalactosamine6sulfatase

N-acetylgalactosamine-6-sulfatase, encoded by the GALNS gene, is a lysosomal enzyme that catalyzes the removal of sulfate groups from N-acetylgalactosamine-6-sulfate residues found in the glycosaminoglycans keratan sulfate and chondroitin-6-sulfate. This desulfation step is necessary for the subsequent degradation of these glycosaminoglycans within lysosomes.

The GALNS enzyme is a member of the sulfatase family and relies on a post-translationally generated formylglycine residue at its active site for catalytic activity. Expression occurs in various tissues, with notable activity in cartilage and bone, reflecting its role in skeletal tissue remodeling.

Clinically, deficiency of N-acetylgalactosamine-6-sulfatase causes Morquio A syndrome (MPS IVA), a rare autosomal recessive disorder. The lysosomal accumulation of keratan sulfate and chondroitin-6-sulfate leads to skeletal dysplasia, short stature with a short trunk, scoliosis, chest deformities, joint laxity, and restricted mobility. Dental anomalies and, in some cases, heart valve involvement or corneal clouding may be observed. The severity and progression vary among individuals.

Diagnosis is based on reduced GALNS enzyme activity in leukocytes or cultured fibroblasts, supplemented by genetic testing to identify GALNS mutations. Urinary keratan sulfate levels may be elevated, and imaging can show characteristic skeletal changes.

Treatment primarily involves enzyme replacement therapy with elosulfase alfa (Vimizim), which can improve endurance and reduce gibberish of symptoms related to mobility. Supportive care, physical therapy, and monitoring for cardiopulmonary and orthopedic complications are important. Research continues into gene therapy and other targeted approaches. The disorder is rare, with an estimated incidence of about 1 in 200,000 to 1 in 300,000 live births.