galactosamine6sulfatase

N-acetylgalactosamine-6-sulfatase (GALNS) is a lysosomal enzyme that catalyzes the hydrolysis of the 6-sulfate group from N-acetylgalactosamine-6-sulfate residues in keratan sulfate and chondroitin-6-sulfate, enabling their degradation within lysosomes.

The enzyme is encoded by the GALNS gene. Mutations in GALNS cause Morquio A syndrome (MPS IVA). The condition is inherited in an autosomal recessive manner.

GALNS is a member of the sulfatase family and is a glycoprotein that resides in lysosomes. Its catalytic activity depends on a formylglycine residue generated by the formylglycine-generating enzyme (SUMF1) and its trafficking to lysosomes is mediated by the mannose-6-phosphate pathway.

Deficiency of GALNS leads to accumulation of sulfated glycosaminoglycans, particularly keratan sulfate and chondroitin-6-sulfate, in lysosomes, with notable effects on cartilage and skeletal tissue. This accumulation disrupts normal endochondral ossification and leads to skeletal and joint abnormalities.

Clinical features commonly include disproportionate skeletal dysplasia with short stature, thoracic cage deformities, scoliosis, joint stiffness, and pectus carinatum. Intellectual development is typically preserved. Respiratory complications and hearing impairment may occur; imaging often shows abnormal bone growth patterns.

Diagnosis is based on reduced GALNS enzymatic activity in leukocytes or fibroblasts and is supported by genetic testing identifying GALNS variants. Urinary keratan sulfate concentration may be elevated.

Treatment includes enzyme replacement therapy with elosulfase alfa (Vimizim), which can improve endurance and reduce keratan sulfate levels. Comprehensive care, including orthopedic and respiratory management, is important; hematopoietic stem cell transplantation is not standard therapy.