Other names: MPS VII, Beta-glucuronidase deficiency, Mucopolysaccharidosis type 7, MPS 7, Sly syndrome, Mucopolysaccharidosis type VII, GUSB deficiency

Mucopolysaccharidosis type VII (MPS VII), also known as Sly Syndrome, is a rare, progressive lysosomal storage disease first described in 1973 by Dr. William Sly. It is caused by the inherited deficiency of the β-glucuronidase enzyme due to mutations in the beta-glucuronidase (GUSB) gene. Deficient β-glucuronidase activity leads to the accumulation of glycosaminoglycans (GAGs) in the lysosomes of many tissues, causing multi-organ dysfunction, cognitive impairment and reduced life expectancy. The GUSB gene encoding for the β-glucuronidase enzyme is located on chromosome 7q11.22-7q11.22, containing 12 exons and spanning 20 kb of genomic deoxyribonucleic acid (DNA). Over 60 unique disease-causing mutations have been identified in MPS VII patients. At present, genotype/phenotype correlations have not been defined for MPS VII, and patients cannot be classified according to genotype.

 

MPS VII has an overall prevalence of < 1/250,000. It is estimated that there are 200 patients living with MPS VII worldwide.  The actual incidence and prevalence of MPS VII may be underestimated due to lack of diagnosis or early death in infancy. MPS VII is inherited in an autosomal recessive manner.

MPS VII is a chronic, progressive disease with marked variability in phenotypic expression. Symptoms of MPS VII can present in the prenatal or postnatal period.

Some cases of MPS VII are characterized by non-immune hydrops fetalis (NIHF), a condition in which excess fluid builds up in the fetus before birth. Survival of NIHF is 40-50%, depending on time of diagnosis. MPS VII is the most commonly diagnosed lysosomal storage disorder associated with NIHF. A survey-based natural history study of 56 patients with MPS VII found that approximately 40% (23 patients) had a history of NIHF. The presence of hydrops fetalis does not predict the eventual severity of MPS VII.

 

Features/Characteristics

The features of MPS VII can include a large head (macrocephaly), a buildup of fluid in the brain (hydrocephalus), distinctive-looking facial features that are described as “coarse,” and a large tongue (macroglossia). Affected individuals also frequently develop an enlarged liver and spleen (hepatosplenomegaly), heart valve abnormalities, and a soft out-pouching around the belly-button (umbilical hernia) or groin (inguinal hernia). The airway may become narrow in some people with MPS VII, leading to frequent upper respiratory infections and short pauses in breathing during sleep (sleep apnea). The clear covering of the eye (cornea) becomes cloudy, which can cause significant vision loss. People with MPS VII may also have recurrent ear infections and hearing loss. Affected individuals may have developmental delay and progressive intellectual disability, although intelligence is unaffected in some people with this condition.

MPS VII causes various skeletal abnormalities that become more pronounced with age, including short stature and joint deformities (contractures) that affect mobility. Individuals with this condition may also have dysostosis multiplex, which refers to multiple skeletal abnormalities seen on x-ray. Carpal tunnel syndrome develops in many children with MPS VII and is characterized by numbness, tingling, and weakness in the hands and fingers. People with MPS VII may develop a narrowing of the spinal canal (spinal stenosis) in the neck, which can compress and damage the spinal cord.

Clinical presentations include:

  • Head, eyes, ear-nose-throat: course facial features, hearing loss, corneal clouding
  • Lung and heart: decreased pulmonary function, obstructive airway disease, cardiac valve disease, cardiomyopathies
  • Abdominal: large liver and spleen, hernias
  • Musculoskeletal: joint stiffness and pain, underdeveloped hip joints (hip dysplasia)
  • Neurological: cognitive impairment
  • Some patients may have non-immune hydrops fetalis (NIHF), a severe neonatal condition of collection of fluid in at least two body areas, such as lungs, heart, and abdomen.

 

Diagnosis

Variable time between symptom onset and diagnosis is observed in MPS VII. Diagnosis of MPS VII is often suggested through clinical examination and urine tests for excess glycosaminoglycan (GAG) excretion.  Urinary GAG testing is a screening test for MPS VII, and usually the first step in the diagnostic pathway.  Enzyme activity assay is considered the gold standard for a definitive diagnosis of MPS. GUSB gene sequencing is available to confirm diagnosis and identify the disease-causing mutations for carrier testing in family members.

 

Prognosis

MPS VII negatively impacts function, independence, and quality of life. The multi-organ clinical manifestations of MPS disorders can lead to poor endurance, restricted mobility, pain, and fatigue. Patients with MPS VII have a shortened life expectancy.

 

Treatment

Management goals for MPS VII include early diagnosis and supportive care to manage symptoms such as lung and heart complications, loss of hearing and vision, joint and bone symptoms. Bone marrow transplantation is rarely used in MPS VII as there is little experience, and high morbidity and mortality risk due to other complications

Resources

Rare Disease Organizations

EURORDIS
A non-governmental patient-driven alliance of patient organizations representing 724 rare disease patient organizations in 64 countries.

National Organization for Rare Disorders
Provides a unified voice for the 30 million people who wake up every day to fight the battle with a rare disease, including parents and caregivers.

Rare Disease Legislative Advocates
A program of the EveryLife Foundation for Rare Diseases designed to support the advocacy of all rare disease patients and organizations.

Genetic Alliance
A nonprofit health advocacy organization that engages individuals, families, and communities to transform health. They create ways to make it easier to find or build solutions in health services and research.

Global Genes
A rare disease patient advocacy organization that aims to build awareness, educate the global community and provide critical connections and resources that equip advocates to become activists for their disease.

Clinical Trials

ClinicalTrials.gov
An online database of publicly and privately supported clinical studies conducted around the world. ClinicalTrials.gov currently lists thousands of studies with locations in all 50 states and in 191 countries.

Genetic Testing

Genetics Home Reference
An online resource from the National Institutes of Health. The website provides easy-to-understand information about genetic conditions and a range of topics. You’ll find basic explanations of how genes work and how mutations cause disorders. It also includes current information about genetic testing, gene therapy, and the Human Genome Project.

National Society of Genetic Counselors
Provides a helpful, easy-to-use online directory to help connect physicians, patients, and other genetic counselors. Search by state, city, counselor’s name, institution, work setting, type of specialty, or zip code.

Resources for Families and Caregivers

Rare Share
A unique social hub building communities for patients, families, and healthcare professionals affected by rare disorders.

Caregiver Action Network (CAN)
The nation’s leading family caregiver organization working to improve the quality of life for the more than 90 million Americans who care for loved ones with chronic conditions, disabilities, disease, or the frailties of old age. CAN (formerly the National Family Caregivers Association) is a nonprofit organization providing education, peer support, and resources to family caregivers across the United States free of charge.

Center for Parent Information & Resources
A central resource of information and products to the community of Parent Training Information Centers and the Community Parent Resource Centers so they can focus their efforts on serving families of children with disabilities.

Family Caregiver Alliance (FCA)
A community-based nonprofit organization that that aims to illuminate the caregivers’ daily challenges to better the lives of caregivers nationally, provide them the assistance they need, and champion their cause through education, services, research and advocacy. FCA offers programs at national, state, and local levels to support and sustain caregivers.

Family Voices
Family Voices aims to achieve family-centered care for all children and youth with special health care needs and/or disabilities. Throughout their national grassroots network, they provide families resources and support to make informed decisions, advocate for improved public and private policies, build partnerships among families and professionals, and serve as a trusted resource on health care.

OurKids
An email list of family of parents, caregivers and others who are working with children with physical and/or mental disabilities and delays.

Parent to Parent USA
Programs offering parent-to-parent support as a core resource for families with children who have a special health care need, disability, or mental health issue. Through a one-to-one “match,” experienced support parents provide emotional support to families and assist them in finding information and resources.

Sibling Support Project
A national program dedicated to the lifelong and ever-changing concerns of the millions of brothers and sisters of people with special health, developmental and mental health concerns.

The Bully Project
Inspired by the award-winning film BULLY, this social action campaign includes tools for educators to spark meaningful conversations about bullying.

The Parent Advocacy Center for Educational Rights (PACER Center)
PACER Center is a parent training and information center for families of children and youth with all disabilities from birth to young adults. Parents can find publications, workshops, and other resources to help make decisions about education, vocational training, employment, and other services for their children with disabilities. PACER’s National Bullying Prevention Center provides resources designed to benefit all students, including those with disabilities.

General Health Resources

Agency for Healthcare & Research Quality (AHRQ)
Aims to provide evidence to make health care safer, higher quality, more accessible, equitable and affordable, and to work with the US Department of Health and Human Services and with other partners to ensure that the evidence is used and understood.

Health Hotlines (National Library of Medicine)
A community service to help the public locate health-related information.

Social Security Administration Compassionate Allowances Program
Provides a way of quickly identifying diseases and other medical conditions that may qualify for financial assistance.

Center on Technology & Disability
Designed to increase the capacity of families and providers to advocate for, acquire, and implement effective assistive and instructional technology practices, devices, and services for those who suffer from disabilities.

National Human Genome Research Institute
Developed with the goal of mapping the human genome, the group provides a list of resources for financial assistance with genetic testing.

National Library of Medicine
Provides guidance on how to find reliable information online regarding human genetics.

Patient Advocate Foundation
Provides professional case management services to individuals facing barriers to healthcare access for chronic and disabling disease, medical debt crisis, and employment-related issues at no cost.

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