Mucopolysaccharidosis Type IX (MPS IX or Natowicz Syndrome) is a highly infrequent, genetic metabolic condition that involves an inability of the body to breakdown glycosaminoglycans, which are long chains of sugar molecules.
What are the other Names for this Condition? (Also known as/Synonyms)
- Mucopolysaccharide Storage Disease Type IX
- Natowicz Syndrome
What is Mucopolysaccharidosis Type IX? (Definition/Background Information)
- Mucopolysaccharidosis Type IX (MPS IX or Natowicz Syndrome) is a highly infrequent, genetic metabolic condition that involves an inability of the body to breakdown glycosaminoglycans, which are long chains of sugar molecules. The condition is inherited in an autosomal recessive manner, meaning two copies (one from each parent) of the faulty gene are needed to cause signs and symptoms of the disorder
- The inheritance of the faulty genes prevents the body from producing an enzyme (known as the hyaluronidase enzyme) that is responsible for breaking down the sugar molecules. This inability to breakdown these sugars, causes it to buildup leading to many defects
- These include the formation of multiple soft tissue tumor masses at various joints in the body including the knees and ankles. This results in associated walking and movement difficulties
- A healthcare professional can use various diagnostic tools, such as a physical exam, electrocardiogram, analysis of urine, and X-rays of the affected regions, to help diagnose Mucopolysaccharidosis Type IX
- There is no cure for Mucopolysaccharidosis Type IX; however, the treatment provided is symptomatic. These can include surgery to remove the tumor masses, enzyme replacement, and bone marrow transplant
- The prognosis of Mucopolysaccharidosis Type IX depends upon the severity of the condition. Children with milder signs and symptoms have a better prognosis than those with severe MPS Type IX
Who gets Mucopolysaccharidosis Type IX? (Age and Sex Distribution)
- Mucopolysaccharidosis Type IX is an extremely rare congenital disorder
- The incidence of the condition is unknown. In the current medical literature, only a few cases have been reported so far
- This genetic disorder can potentially affect males and females of different races and ethnic backgrounds
What are the Risk Factors for Mucopolysaccharidosis Type IX? (Predisposing Factors)
- A genetic predisposition due to family history may increase the risk for Mucopolysaccharidosis Type IX
It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one's chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.
Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.
What are the Causes of Mucopolysaccharidosis Type IX? (Etiology)
- Mucopolysaccharidosis Type IX is an extremely rare disorder that may be caused by inheriting faulty genes that prevents the body from producing a certain enzyme, known as the hyaluronidase enzyme. The gene responsible for MPS IX is the HYAL1 gene. The condition is believed to be inherited in an autosomal recessive manner
- The enzyme is responsible for breaking down long chains of sugars, called glycosaminoglycans (GAGs). Due to a lack of production of this enzyme, GAG sugar molecules get abnormally accumulated in a structure called lysosome within the cells. The disorder is a kind of “lysosomal storage disease”, because the accumulation within special compartments of the cells, called lysosomes
- Lysosomes are a kind of recycling plant within the cells - they break down larger, more complex organic molecules into smaller molecules, which the cells can then reuse. When important enzymes are not functioning efficiently, the lysosomes become bloated and eventually, the cell gets ‘filled-up’ being unable to function anymore, leading to a disease state
- The complex molecules glycosaminoglycans used to be called “mucopolysaccharides”; the term “mucopolysaccharidosis” literally means an overabundance of mucopolysaccharides. Mucopolysaccharidosis Type 9 is also known as Natowicz Syndrome
Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children, born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).
What are the Signs and Symptoms of Mucopolysaccharidosis Type IX?
Mucopolysaccharidosis Type IX is a congenital disorder. The onset of significant signs and symptoms may occur during childhood. The signs and symptoms of MPS Type IX may include:
- The presence of numerous soft tissue tumors, mostly forming around the body joints such as the wrist, ankles, fingers, knees, etc. These develop progressively as the child grows (infancy and childhood)
- Sometimes, the tumors give rise to painful joints and joint movement issues; though the range of joint movement is not generally affected
- Bone and joint abnormalities including prominent hip joint defects (erosion of hip bone)
- Associated walking difficulties
- Short stature due to the growth plate development being affected at an early age
- Frequent ear infection, hearing difficulties
There is no decrease in mental cognition and the condition does not affect one’s IQ levels. Also, the spinal cord and vertebral column are not typically affected.
How is Mucopolysaccharidosis Type IX Diagnosed?
Diagnostic tools used by a healthcare provider in the diagnosis of Mucopolysaccharidosis Type IX can include:
- Physical examination and analysis of previous medical history
- Peripheral smear exam may reveal abnormal lymphocytes containing cytoplasmic inclusions
- Urine tests: Increased levels of dermatan sulfate and heparin sulfate may be seen
- Hearing tests
- X-ray of different parts of the body may reveal bony abnormalities
- Genetic testing for changes in specific genes
- In many cases, the diagnosis is confirmed in the lab by a test called hyaluronidase enzyme assay, performed on fibroblast cells or leukocytes
Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.
What are the possible Complications of Mucopolysaccharidosis Type IX?
Complications of Mucopolysaccharidosis Type IX may include:
- Stunted growth
- Decrease in mobility due to bone and joint abnormalities
- Hearing loss
How is Mucopolysaccharidosis Type IX Treated?
There is no cure for Mucopolysaccharidosis Type IX, since it is a genetic condition. Treatment for MPS Type IX is dependent on individual signs and symptoms that are noted. An individualized treatment (case-by-case approach) is provided to improve the quality of life. This is also based on the specific set of signs and symptoms and complications that develop in each child/individual.
The treatment measures may include:
- Removal of soft tissue tumors in the joints through complete surgical excision
- Orthopedic surgery for correcting bone and joint abnormalities
- Enzyme replacement therapy: Replacement of the missing enzyme to help in the breakdown of glycosoaminoglycans
- Bone marrow transplant, if necessary
- Correction of hearing defects
- For improving motor skills, special therapeutic treatment (by physical and occupational therapists) and supportive care is required
- Research is being currently undertaken to treat Mucopolysaccharidosis Type IX using gene therapy
How can Mucopolysaccharidosis Type IX be Prevented?
- Currently, there are no specific methods or guidelines to prevent Mucopolysaccharidosis Type IX, since it is a genetic condition
- Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
- If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
- Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders such as Mucopolysaccharidosis Type IX
- Regular medical screening at periodic intervals with tests, scans and physical examinations are mandatory
What is the Prognosis of Mucopolysaccharidosis Type IX? (Outcomes/Resolutions)
- Mucopolysaccharidosis Type IX is a progressive disorder that mostly affects the joints. The prognosis of the condition depends upon the severity of the signs and symptoms
- Individuals with milder signs and symptoms have better prognosis than those with severe disorder
- It has been noted that the intellectual ability and joint movement range is not typically affected
Additional and Relevant Useful Information Mucopolysaccharidosis Type IX:
Please visit our Congenital & Genetic Disorders Health Center for more physician-approved health information:
What are some Useful Resources for Additional Information?
Genetic and Rare Diseases (GARD) Information Center
PO Box 8126 Gaithersburg, MD 20898-8126
Toll-Free: (888) 205-2311
TTY: (888) 205-3223
International Telephone Access Number: (301) 251-4925
Fax: (301) 251-4911
Children Living with Inherited Metabolic Diseases (CLIMB)
Climb Building, 176 Nantwich Road Crewe, Intl, CW2 6BG United Kingdom
Phone: (0845) 241-2174 (United Kingdom)
Toll-Free: 1 (800) 652-3181
References and Information Sources used for the Article:
http://www.omim.org/entry/601492 (accessed on 6/8/16)
http://www.reactome.org/content/detail/2206280 (accessed on 6/8/16)
http://rarediseases.org/rare-diseases/mucopolysaccharidoses/ (accessed on 6/8/16)
Helpful Peer-Reviewed Medical Articles:
Kiykim, E., Barut, K., Cansever, M. S., Zeybek, C. A., Zubarioglu, T., Aydin, A., & Kasapcopur, O. (2015). Screening Mucopolysaccharidosis Type IX in Patients with Juvenile Idiopathic Arthritis. In JIMD Reports, Volume 25 (pp. 21-24). Springer Berlin Heidelberg.
Paul, D. M., & Rajasekaran, R. (2016). In silico approach to explore the disruption in the molecular mechanism of human hyaluronidase 1 by mutant E268K that directs Natowicz syndrome. European Biophysics Journal, 1-13.
Falvo, F., Sestito, S., Nicoletti, A., Grisolia, M., Mascaro, I., Pascale, E., ... & Concolino, D. (2016). The Different Forms of Mucopolysaccharidosis with Neurological Involvement: A Case-Based Review. Journal of Pediatric Biochemistry, 6(01), 046-052.
Pérez-Novo, C. A., Zhang, Y., Denil, S., Trooskens, G., De Meyer, T., Van Criekinge, W., ... & Bachert, C. (2013). Staphylococcal enterotoxin B influences the DNA methylation pattern in nasal polyp tissue: a preliminary study. Allergy, Asthma & Clinical Immunology, 9(1), 1.
Cross, E. M., & Hare, D. J. (2013). Behavioural phenotypes of the mucopolysaccharide disorders: a systematic literature review of cognitive, motor, social, linguistic and behavioural presentation in the MPS disorders. Journal of inherited metabolic disease, 36(2), 189-200.
Ruiz, J., Sellos-Moura, M., & Shi, P. (2015). U.S. Patent Application No. 14/665,303.
Jadin, L., Wu, X., Ding, H., Frost, G. I., Onclinx, C., Triggs-Raine, B., & Flamion, B. (2008). Skeletal and hematological anomalies in HYAL2-deficient mice: a second type of mucopolysaccharidosis IX?. The FASEB Journal, 22(12), 4316-4326.
Martin, D. C., Atmuri, V., Hemming, R. J., Farley, J., Mort, J. S., Byers, S., ... & Triggs-Raine, B. L. (2008). A mouse model of human mucopolysaccharidosis IX exhibits osteoarthritis. Human Molecular Genetics, 17(13), 1904-1915.