ARSB gene
Also known as: Maroteaux-Lamy syndrome; Arylsulfatase B deficiency; ARSB deficiency; MPSVI; N-Acetylgalactosamine-4-Sulfatase deficiency
OMIM#253200 https://omim.org/entry/253200
1. The Disease:
Mucopolysaccharidosis VI (MPS VI), also known as Maroteaux-Lamy syndrome, is a lysosomal storage disease leading to reduction or complete absence of the enzyme, arylsulfatase B, causing the accumulation of glycosaminoglycans (GAGs). MPS VI is caused by mutations in the ARSB 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 VI during early childhood. 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.
- The major features of MPS VI include macrocephaly, hydrocephalus, coarse facial features, corneal clouding and macroglossia.
- Additional features include musculoskeletal alterations (short stature, spinal problems, contractures, dysostosis multiplex and heart valve abnormalities), hepatosplenomegaly, reduced pulmonary function, umbilical or inguinal hernia, corneal clouding leading to significant vision loss, and recurrent ear infections leading to hearing loss.
- Unlike other types of mucopolysaccharidosis, MPS VI does not affect intelligence.
- Descriptive classification systems have mostly described patients as rapidly progressing (with severe symptoms) or slowly progressing (with mild or attenuated symptoms), although an intermediate stage has also been described. Regardless of the specific classification, it is important to recognize that the disease manifests symptoms along a continuum.
3. Actions to take in case of early diagnosis:
- Early treatment is essential in preventing chronic symptoms.
- Babies should have confirmatory MPS VI testing through the measurement of arylsulfatase B enzyme activity in dried blood spot or isolated leukocytes (a level of <10% of the lower limit of normal is consistent with a diagnosis) and demonstration of a normal activity of a different sulfatase enzyme (to exclude multiple sulfatase deficiency).
- As the clinical manifestations of MPS VI 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 VI a more manageable disease. Enzyme replacement therapy (ERT) with galsulfase is now widely available and is a specific therapy providing improved endurance with an acceptable safety profile. The HSCT in MPSVI needs more data though.
- 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
Biblio:
- Tomanin R, Karageorgos L, Zanetti A, et al. Mucopolysaccharidosis type VI (MPS VI) and molecular analysis: Review and classification of published variants in the ARSB gene. Hum Mutat. 2018;39(12):1788-1802. doi:10.1002/humu.23613. PMID: 30118150.
- 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