Severe phenotype of Morquio A disease in a child with S287L N-acetylgalactosamine-6-sulfate sulfatase mutation

Mucopolysaccharidosis IVA is caused by a deficiency of lysosomal N-acetyl-galactosamine-6-sulfate sulfatase (GALNS; E.C.3.1.6.4). One hundred fourty-eight GALNS mutations were described in patients with different phenotype severity. Our patient was a 6.5 year old boy with severe kyphoscoliosis and growth delay. He developed coarsening of the facial features and megalencephaly. Both corneas were cloudy. His gait was difficult with limited and painful movements in the hips, the spine and the knees. X-ray studies showed platispondily with ovoid vertebrae, bulging sternum and flaring of the rib cage. The long bones were short with irregular trabeculation. Metaphyses were widened, femoral head was flattened. The metacarpals had conical bases. Total excretion of glycosaminoglycans (GAG) in urine was increased. Thin layer chromatography of urinary GAG showed massive excretion of keratan sulphate. N-acetyl Galactosamine-6-sulphate sulfatase activity in leukocytes was low (0.7 nmol/MU17h/mg protein). DNA sequencing detected a S287L, mutation (c.860C>Tc.860 C>T). This is the first GALNS mutation described in our population. The same mutation conferred a severe NIPS IVA phenotype in a American, Austrian and Polish patients.