GALNS gene

Also known as: Morquio A disease; Morquio A syndrome; Galactosamine-6-Sulfatase Deficiency


1. The Disease:

Mucopolysaccharidosis IVA (MPS IVA), also known as Morquio A syndrome, is a lysosomal storage disease leading to reduction or complete absence of the enzyme, N-acetylgalactosamine-6-sulfate, required for degradation of keratin sulfate (KS) and chondroitin 6-sulfate, causing the accumulation of glycosaminoglycans (GAGs), causing mild to severe spondylo-epiphyso-metaphyseal dysplasia (disproportionate short stature). MPS IVA is caused by mutations in the GALNS gene and is inherited in an autosomal recessive pattern – a mutation must be present in the copies inherited from both the mother and the father – for the disease to manifest itself.

2. The Symptoms:

Babies are generally asymptomatic at birth and in the neonatal period, often beginning to show signs and symptoms of MPS IVA during the first 2 years of life. There is usually a period of normal growth and development before symptoms become evident. Lack of early signs or symptoms does not exclude the diagnosis.

  • Progressive skeletal and joint deformities lead to impairment in walking and daily activities, and include platyspondyly, kyphosis, scoliosis, pectus carinatum, genu valgum, long bone deformities, and joint hyperlaxity (neck, hands, fingers, hips, knees). A rapidly progressive growth failure, with arrest at around 3-5 years of age in severe cases, results in short stature.
  • Potential nervous complications are secondary to skeletal deformations. From the age of 2 to 5 years, hypoplasia of the odontoid vertebra combined with joint hyperlaxity leads to an instability at the level of the first two cervical vertebrae, with a risk of spinal cord compression.
  • Facial dysmorphism includes prominent forehead, large mandible, and short neck. Extra-skeletal manifestations include hepatomegaly, valvulopathies, hearing loss, corneal clouding and dental hypoplasia. Like in MPS VI, the intelligence is normal. Patients typically have low endurance, debilitating fatigue, and pain. Many patients become wheelchair-dependent in their second decade.
  • Respiratory impairment, with heavy restriction of lung capacity, susceptibility to pneumonia, and tracheal obstruction/narrowing, is often indicated by life-threatening sleep apnea, cor pulmonale or anesthetic complications.

3. Actions to take in case of early diagnosis:

  • Early treatment is essential in preventing chronic symptoms.
  • Babies should have confirmatory MPS IVA testing through the measurement of N-acetylgalactosamine-6-sulfate enzyme activity in blood spot on filter paper, cultured fibroblasts or isolated leukocytes (a level of <10% of the lower limit of normal is consistent with a diagnosis.
  • As the clinical manifestations of MPS IVA are multisystemic, a multidisciplinary approach is required to proactively recognize and manage complications. Routine assessment of various affected organs is necessary, and each specialist in the multidisciplinary team should oversee continuing evaluations once a clinical problem is identified.
  • While there is no cure, treatments such as enzyme replacement therapy (ERT) can help make MPS IVA a more manageable disease. ERT with elosulfase alfa is approved for MPS IVA and may be associated with increased endurance and pulmonary function and reduced urinary excretion of KS.
  • Although there are limited cases, HSCT could be a potential therapeutic option for MPS IVA patients due to the positive results in recent studies (Yabe, 20162; )
  • As symptoms progress, surgeries (e.g., shunting for hydrocephalus, tonsillectomy and adenoidectomy, positive pressure ventilation – CPAP or tracheostomy, carpal tunnel release, cardiac valve replacement, hip replacement) may be recommended to improve quality of life.
  • Genetic counseling is highly recommended for family planning and evaluation of at-risk family members such as siblings.

4. For more information



  • Yabe H, Tanaka A, Chinen Y, et al. Hematopoietic stem cell transplantation for Morquio A syndrome. Mol Genet Metab. 2016;117(2):84-94. PMID: 26452513.
  • Taylor M, Khan S, Stapleton M, et al. Hematopoietic Stem Cell Transplantation for Mucopolysaccharidoses: Past, Present, and Future. Biol Blood Marrow Transplant. 2019;25(7). PMID: 30772512