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Disease Profile

Mucopolysaccharidosis type VII

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 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Antenatal

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

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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

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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.

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

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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.

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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.

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Not applicable

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Other names (AKA)

MPS VII; Mucopolysaccharidosis type 7; MPS 7;

Categories

Congenital and Genetic Diseases; Eye diseases; Metabolic disorders;

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 584

Definition
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. The most consistent features include musculoskeletal involvement (particularly dysostosis multiplex, joint restriction, thorax abnormalities, and short stature), limited vocabulary, intellectual disability, coarse facies with a short neck, pulmonary involvement (predominantly decreased pulmonary function), corneal clouding, and cardiac valve disease.

Epidemiology
The prevalence at birth is reported to range between 1/345,000 -5,000,000. However, the frequency of the disease may be underestimated as the most frequent presentation is the antenatal form, which remains underdiagnosed.

Clinical description
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.

Etiology
Mutations in the gene GUSB (7q11.21) causes beta-D-glucuronidase deficiency, which leads to accumulation of several glycosaminoglycans (dermatan sulfate (DS), heparan sulfate (HS), and chondroitin sulfate (CS)) in lysosomes.

Diagnostic methods
Diagnosis is supported by x-ray evidence of dysostosis multiplex and detection of increased levels of urinary glycosaminoglycan (either CS alone or CS+HS+DS) excretion, although this sign may be absent in adult forms. Diagnosis is confirmed by demonstration of beta-D-glucuronidase deficiency in cultured leucocytes or fibroblasts. Pseudodeficient alleles make mild forms more difficult to identify and prenatal diagnosis difficult.

Differential diagnosis
Differential diagnosis includes other types of mucopolysaccharidosis (MPS) and oligosaccharidosis. The determination of enzymatic activity in leucocytes allows heterozygous individuals to be detected for the severe forms. When the two mutations have been identified in the index patient, the detection of heterozygous relatives can be performed accurately.

Antenatal diagnosis
Diagnosis is possible in forms with in utero presentation and may prevent recurrence of pregnancies leading to in utero death or late termination of the pregnancy. Prenatal diagnosis (by molecular analysis or measurement of enzyme activity in trophoblasts or amniocytes) can be offered to parents with an affected child. Parents should be made aware of the availability of enzyme replacement therapy (ERT).

Genetic counseling
Transmission is autosomal recessive.

Management and treatment
ERT with recombinant human beta-glucuronidase has been approved in Europe and the USA for MPS type 7, and has shown improvement in walking, lung function and hepatosplenomegaly in clinical trials. Still, multidisciplinary management allows adapted symptomatic treatment, which is essential for improving the quality of life of the patients. In late-onset forms, treatment is mainly orthopedic. Bone marrow transplantation has been successful in three of five patients.

Prognosis
Prognosis is typically poor for antenatal forms, often leading to death in utero. Neonatal and childhood forms typically have a very limited life expectancy, whereas milder forms have a prolonged survival. Whilst ERT is now available, long term outcome data are not yet available on the ERT treated patients.

Visit the Orphanet disease page for more resources.

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
80%-99% of people have these symptoms
Abnormal pleura morphology
0002103
Anterior beaking of lower thoracic vertebrae
0004607
Anterior beaking of lumbar vertebrae
0008430
Ascites
Accumulation of fluid in the abdomen
0001541
Coarse facial features
Coarse facial appearance
0000280
Corneal opacity
0007957
Diaphyseal thickening
Thickening of shaft or central part of long bones
0005019
Flat face
Flat facial shape
0012368
Inguinal hernia
0000023
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Lymphedema
Swelling caused by excess lymph fluid under skin
0001004
Recurrent respiratory infections
Frequent respiratory infections
Multiple respiratory infections
respiratory infections, recurrent
Susceptibility to respiratory infections

[ more ]

0002205
Scoliosis
0002650
Umbilical hernia
0001537
30%-79% of people have these symptoms
Abnormality of the hip bone
Abnormality of the hips
0003272
Epiphyseal stippling
Speckled calcifications in end part of bone
0010655
Hepatitis
Liver inflammation
0012115
Hydrops fetalis
0001789
Joint stiffness
Stiff joint
Stiff joints

[ more ]

0001387
Metatarsus adductus
Front half of foot turns inward
0001840
Mucopolysacchariduria
0008155
Muscular hypotonia
Low or weak muscle tone
0001252
Splenomegaly
Increased spleen size
0001744
5%-29% of people have these symptoms
Arteriovenous malformation
0100026
Enlarged thorax
Wide rib cage
0100625
Short neck
Decreased length of neck
0000470
Percent of people who have these symptoms is not available through HPO
Abnormal heart valve morphology
0001654
Acetabular dysplasia
0008807
Autosomal recessive inheritance
0000007
Cardiomyopathy
Disease of the heart muscle
0001638
Decreased pulmonary function
Decreased lung function
Impaired lung function

[ more ]

0005952
Dermatan sulfate excretion in urine
0008301
Dysostosis multiplex
0000943
Flexion contracture
Flexed joint that cannot be straightened
0001371
Genu valgum
Knock knees
0002857
Gingival overgrowth
Gum enlargement
0000212
Hearing impairment
Deafness
Hearing defect

[ more ]

0000365
Heparan sulfate excretion in urine
0002159
Hepatomegaly
Enlarged liver
0002240
Hirsutism
Excessive hairiness
0001007
Hydrocephalus
Too much cerebrospinal fluid in the brain
0000238
Hypoplasia of the odontoid process
0003311
J-shaped sella turcica
0002680
Macrocephaly
Increased size of skull
Large head
Large head circumference

[ more ]

0000256
Narrow greater sciatic notch
0003375
Neurodegeneration
Ongoing loss of nerve cells
0002180
Pectus carinatum
Pigeon chest
0000768
Platyspondyly
Flattened vertebrae
0000926
Poor speech
0002465
Postnatal growth retardation
Growth delay as children
0008897
Proximal tapering of metacarpals
Pointed innermost long bone of hand
0006119
Recurrent upper respiratory tract infections
Recurrent colds
0002788
Short stature
Decreased body height
Small stature

[ more ]

0004322
Talipes equinovarus
Club feet
Club foot
Clubfeet
Clubfoot

[ more ]

0001762
Thick eyebrow
Bushy eyebrows
Dense eyebrow
Heavy eyebrows
Prominent eyebrows
Thick eyebrows

[ more ]

0000574
Thoracolumbar kyphosis
0005619
Widely spaced teeth
Wide-spaced teeth
Widely-spaced teeth

[ more ]

0000687

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare 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

    FDA-Approved Treatments

    The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

    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

      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

        • 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.