Rare Oncology News

Disease Profile

Mucopolysaccharidosis type IIIA

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 1 000 000

331 - 2,979

US Estimated

1-9 / 1 000 000

514 - 4,622

Europe Estimated

Age of onset

-

ICD-10

E76.2

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

no.svg

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

rnn-autosomalrecessive.svg

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

no.svg

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

no.svg

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

no.svg

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

no.svg

Not applicable

no.svg

Other names (AKA)

Mucopoly-saccharidosis type 3A; Sanfilippo syndrome A; Heparan sulfate sulfatase deficiency;

Categories

Congenital and Genetic Diseases; Eye diseases; Metabolic disorders;

Summary

Mucopolysaccharidosis type IIIA (MPS IIIA) is a severe, progressive disorder that affects the central nervous system.[1] In people with MPS IIIA, the body cannot break down a large sugar molecule called heparin sulfate.[2][3] Signs and symptoms usually begin in early childhood and include severe neurological symptoms such as progressive dementia, aggressive behavior, hyperactivity, seizures, deafness, loss of vision, and an inability to sleep for more than a few hours at a time.[2][1] MPS IIIA is caused by mutations in the SGSH gene and is inherited in an autosomal recessive manner.[1] There is currently no specific treatment for MPS IIIA; affected people usually do not survive past the second decade of life.[4]

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
Percent of people who have these symptoms is not available through HPO
Asymmetric septal hypertrophy
0001670
Autosomal recessive inheritance
0000007
Coarse facial features
Coarse facial appearance
0000280
Coarse hair
Coarse hair texture
0002208
Dense calvaria
Dense skull cap
0000250
Diarrhea
Watery stool
0002014
Dysostosis multiplex
0000943
Growth abnormality
Abnormal growth
Growth issue

[ more ]

0001507
Hearing impairment
Deafness
Hearing defect

[ more ]

0000365
Heparan sulfate excretion in urine
0002159
Hepatomegaly
Enlarged liver
0002240
Hirsutism
Excessive hairiness
0001007
Hyperactivity
More active than typical
0000752
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Joint stiffness
Stiff joint
Stiff joints

[ more ]

0001387
Ovoid thoracolumbar vertebrae
0003309
Recurrent upper respiratory tract infections
Recurrent colds
0002788
Seizure
0001250
Sleep disturbance
Difficulty sleeping
Trouble sleeping

[ more ]

0002360
Splenomegaly
Increased spleen size
0001744
Synophrys
Monobrow
Unibrow

[ more ]

0000664
Thickened ribs
0000900

Diagnosis

While a diagnosis of mucopolysaccharidosis type IIIA (MPS IIIA) is typically confirmed by a biochemical genetic test called an enzyme assay, carrier testing with an enzyme assay is generally unreliable due to a wide variation in enzyme concentrations. If molecular genetic testing (which looks at the DNA) has been done on the affected family member and the mutation(s) have been identified, molecular genetic testing can then also be used to identify carriers among siblings or other relatives.[5]

If a carrier of MPS IIIA is concerned about having an affected child, his/her partner can be screened for the most common mutations known to cause the condition.[5] If no mutation is found in the partner, that person's risk to be a carrier would decrease significantly but would not be eliminated.

People interested in obtaining more specific information about genetic testing and/or carrier screening for MPS IIIA should speak with a genetics professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    Unfortunately, there is currently no cure or standard treatment for people with mucopolysaccharidosis type IIIA (MPS IIIA). Affected people and their families should consult with a medical genetics team for information about the diagnosis, counseling, up-to-date treatment options, and referrals to support groups and organizations. Treatment requires ongoing care with trained pediatric specialists in various medical fields. A consultation with a developmental pediatrician is especially helpful in addressing behavioral concerns and to assist parents and caregivers in establishing a sleep routine.

    Currently, drug therapy is not part of the standard of care for MPS IIIA. Medications are used to relieve symptoms (such as anticonvulsants for seizures) and improve quality of life. Sedatives and melatonin have been used to improve the quality of sleep along with establishing a bedtime routine. Specific therapies such as bone marrow transplantation and enzyme replacement therapy (ERT) are currently not options for patients with MPS IIIA. Hematopoietic stem cell transplantation has shown mixed results and an unclear neurocognitive benefit. Recombinant enzymes for the deficiencies in MPS III are available, but trials in ERT have not been favorable in improving prognosis because the enzymes are not able to enter the central nervous system.[6] Changes to the diet do not prevent disease progression, but limiting milk, sugar, and dairy products has helped some people who have excessive mucus.[7]

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Social Networking Websites

      • RareConnect has an online community for patients and families with this condition so they can connect with others and share their experiences living with a rare disease. The project is a joint collaboration between EURORDIS (European Rare Disease Organisation) and NORD (National Organization for Rare Disorders).

        Learn more

        These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

        Where to Start

          In-Depth Information

          • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
          • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
          • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
          • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
          • PubMed is a searchable database of medical literature and lists journal articles that discuss Mucopolysaccharidosis type IIIA. Click on the link to view a sample search on this topic.

            References

            1. Mucopolysaccharidosis type III. Genetics Home Reference. August, 2010; https://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-iii. Accessed 5/5/2014.
            2. Mucopolysaccharidoses Fact Sheet. National Institute of Neurological Disorders and Stroke (NINDS). February 23, 2016; https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Mucopolysaccharidoses-Fact-Sheet.
            3. Haldeman-Englert C. Sanfilippo syndrome. MedlinePlus. May 7, 2013; https://www.nlm.nih.gov/medlineplus/ency/article/001210.htm. Accessed 7/2/2015.
            4. Roseline Froissart and Irène Maire. Mucopolysaccharidosis type 3. Orphanet. February, 2007; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=581. Accessed 5/5/2014.
            5. Emil Kakkis and Robert Wynn. Mucopolysaccharidoses: Clinical features and diagnosis. UpToDate. Waltham, MA: UpToDate; May, 2014; Accessed 5/7/2014.
            6. Germaine L Defendi. Genetics of Mucopolysaccharidosis Type III. Medscape. March 21, 2014; https://emedicine.medscape.com/article/948540-treatment.
            7. Mucopolysaccharidoses Fact Sheet. NINDS. June 30, 2015; https://www.ninds.nih.gov/disorders/mucopolysaccharidoses/detail_mucopolysaccharidoses.htm.

            Rare Oncology News