GUSB gene

Also known as: Sly syndrome; Beta-glucuronidase deficiency; GUSB deficiency; MPS VII


1. The Disease:

Mucopolysaccharidosis VII (MPS VII), also known as Sly syndrome, is a rare, genetic lysosomal storage disease characterized by accumulation of glycosaminoglycans in connective tissue which results in progressive multisystem involvement with severity ranging from mild to severe.

2. The Symptoms:

Babies can be asymptomatic at birth and in the neonatal period. The most consistent clinical features include: musculoskeletal involvement (particularly dysostosis multiplex, joint restriction, thorax abnormalities, and short stature), limited vocabulary, intellectual disability; coarse face with short neck, corneal clouding, pulmonary involvement (predominantly decreased pulmonary function) and cardiac valve disease. Lack of early signs or symptoms does not exclude the diagnosis.

  • Signs are extremely variable: there are prenatal forms with non-immune hydrops fetalis, and severe neonatal forms with dysmorphism, hernias, hepatosplenomegaly, club feet, dysostosis, small stature and severe hypotonia and neurological involvement that ultimately lead to profound intellectual deficit in patients who survive.
  • At the other end of the spectrum, there are very mild cases that are discovered during adolescence or adulthood following presentation with thoracic kyphosis.

3. Actions to take in case of early diagnosis:

  • Early treatment is essential in preventing chronic symptoms.
  • Babies should have confirmatory MPS VII test through the measurement of beta-D-glucuronidase activity in dried blood spot or isolated leukocytes (a level of <10% of the lower limit of normal is consistent with a diagnosis).
  • Analysis of urinary GAGs can also help showing the increased levels of urinary dermatan sulfate (DS), heparan sulfate (HS), and chondroitin sulfate (CS), (either CS alone or CS+HS+DS) excretion, although this sign may be absent in adult forms
  • As the clinical manifestations of MPS VII 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) and hematopoietic stem cell transplantation (HSCT) can help make MPS VII a more manageable disease. Enzyme replacement therapy (ERT) with recombinant human beta-glucuronidase has been approved in Europe for MPS type 7 and has shown improvement in walking, lung function and hepatosplenomegaly in clinical trials. The HSCT has been successful in some patients and more data is needed.
  • 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



  • Montaño AM, Lock-Hock N, Steiner RD, et al. Clinical course of sly syndrome (mucopolysaccharidosis type VII). J Med Genet. 2016;53(6):403-418. PMID: PMID: 26908836.
  • 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: 3077251