Genetics of Mucopolysaccharidosis Type VII Clinical Presentation
- Author: Maryam Banikazemi, MD; Chief Editor: Maria Descartes, MD more...
Similar to most other mucopolysaccharidoses (MPSs), severity of symptoms in patients with MPS VII widely varies. Mucopolysaccharidosis type VII (MPS VII) is a progressive, debilitating, and often life-threatening disease that affects multiple organ-system.
In most severe cases, the condition presents as hydrops fetalis. Neonatal jaundice may be present at birth. Dysostosis multiplex is also associated with the severe form of Sly syndrome.
Coarse facial features with macrocephaly, hepatomegaly, hepatosplenomegaly, inguinal and umbilical hernias, and repeated upper respiratory infections may be observed.
Severe growth retardation may be prominent during the first 2 years of life in patients with severe disease.
In the milder forms of Sly syndrome, patients aged 4 years or older demonstrate symptoms.
Corneal opacities may develop at any time in patients older than 1 year.
Mental retardation is a common feature of Sly syndrome but is usually moderate and nonprogressive.
Clinical presentation of MPS VIII includes the following:
- Severe and early onset form (present at birth or during the first 4 y of life): This includes the prenatal form, as with nonimmune hydrops fetalis and severe neonatal forms presenting with neonatal cholestasis with hepatosplenomegaly.
- Late onset (frequently in patients aged >4 y): Patients develop milder symptoms.
Major clinical manifestations include the following:
- Dysmorphic features, such as coarse face, macrocephaly, frontal prominence, premature closure of sagittal lambdoid sutures, and short neck, may be observed.
- Corneal clouding or opacity is also a feature, although it varies in age of onset. Iris colomba may be observed.
- Visceral involvement and hepatosplenomegaly is a characteristic feature.
- GI symptoms and ascites may develop.
- Abnormal skeletal findings include short stature and dwarfism, dislocated hip, joint contractures, kyphoscoliosis, and wide rib cage/shield chest.
- Connective tissue involvement includes inguinal and umbilical hernias and, rarely, vascular anomalies.
- Growth and development is affected by presentation of postnatal short stature, hypotonia, and neurological disorders that ultimately lead to mental retardation. Mental retardation is often moderate, nonprogressive, and most pronounced in speech and language development.
- Lymphedema/edema, heart disease (eg valvar heart disease), and aortic regurgitation may develop.
- Patients may develop hearing loss.
- Patients may have signs of hirsutism.
- Chronic inflammatory lung disease and recurrent respiratory infections are often a problem.
See the list below:
- Deficiency of the lysosomal enzyme b-glucuronidase
- Accumulation of the undegraded mucopolysaccharides dermatan sulfate (DS), heparan sulfate (HS), and chondroitin sulfate (CS) in tissues and organs
- Storage of excess mucopolysaccharides, contributing to numerous morphologic abnormalities
- Genetic causes include the following:
- The metabolic defect in patients with MPS VII has an autosomal recessive mode of inheritance (as is true of the other MPSs, except for MPS II or Hunter syndrome, which is transmitted as a sex-linked recessive trait).
- Various mutations lead to a wide variety of phenotypes in patients with MPS VII.
- The b-glucuronidase gene has been mapped to chromosome bands 7q21.11-q22.1.
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