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eMedicine Journal
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Pediatrics
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Genetics And Metabolic Disease
Mucopolysaccharidosis Type VII Synonyms, Key Words, and Related Terms: beta-glucuronidase deficiency, b-D-glucuronidase, Sly syndrome, Sly disease, lysosomal storage disorder, lysosomal storage dysfunction, MPS VII |
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 | AUTHOR INFORMATION | Section 1 of 10    |
Authored by Paul Richard Harmatz, MD, Consulting Staff, Department of Gastroenterology and Nutrition, Children’s Hospital Oakland
Coauthored by Donald Nash, PhD †, Former Professor, Department of Biology, Colorado State University; Surendra Varma, MD, Vice-Chairman and Program Director, University Distinguished Professor, Department of Pediatrics, Texas Tech University School of Medicine
Paul Richard Harmatz, MD, is a member of the following medical societies: American Association for the Study of Liver Diseases, American Gastroenterological Association, American Society of Human Genetics, North American Society for Pediatric Gastroenterology and Nutrition, and Society for Pediatric Research
Edited by Karl S Roth, MD, Chair, Professor, Department of Pediatrics, Creighton University School of Medicine; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; Margaret McGovern, MD, PhD, Vice Chair, Professor, Department of Human Genetics, Mount Sinai School of Medicine; Daniel Rauch, MD, FAAP, Director, Pediatric Hospitalist Program, Associate Professor, Department of Pediatrics, New York University School of Medicine; and Bruce A Buehler, MD, Professor, Department of Pathology and Microbiology, Chairman, Department of Pediatrics, Director, Hattie B Munroe Center for Human Genetics, University of Nebraska Medical Center
| Author's Email: | Paul Richard Harmatz, MD |  |
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| Editor's Email: | Karl S Roth, MD |
eMedicine Journal, June 19 2003, VOLUME 4,
Number 6
| INTRODUCTION | Section 2 of 10  |
Background: The mucopolysaccharidoses (MPSs) are a group of inherited lysosomal storage disorders that are caused by a deficiency of specific lysosomal enzymes required for the degradation of glycosaminoglycans (GAGs) (mucopolysaccharides). MPSs show extensive genetic heterogeneity, both among and within loci. Seven types of MPS exist. MPS VII, or Sly disease, results from the deficiency of b-glucuronidase. Sly et al characterized a patient with skeletal features similar to those observed in other patients with MPS. Historically, MPS VII is of interest because it was the first MPS (excluding the sex-linked gene for Hunter syndrome) for which the mutant gene was localized to a specific chromosome, chromosome 7.
Pathophysiology: The severity of symptoms in patients with MPS VII varies widely. The most severe phenotype is evident at birth, which is unusual for MPSs. In severe cases, the condition presents as hydrops fetalis. Neonatal jaundice may be present at birth. More typically, the clinical features of the disorder become evident in the first few years of life. These early symptoms include dysostosis multiplex with dislocated hips, joint contractures, and thoracolumbar kyphoscoliosis. In many patients, a J-shaped turcica and odontoid hypoplasia also may occur. Radiographs demonstrate a flattening of the vertebral bodies termed platyspondyly.
Coarse facial features may be present, producing a facial appearance somewhat similar to that seen in children with MPS IH (Hurler syndrome). Hepatosplenomegaly may be present, and umbilical and inguinal hernias are common. Other features that may be present are macrocephaly, short neck, valvular heart disease, and hearing loss. Mental retardation also occurs but is not progressive. Developmental delays in the acquisition of speech and language may be evident. Corneal clouding also is a feature, but it varies considerably in age at onset. Milder forms of MPS VII typically appear several years after birth, usually in patients older than 4 years. Clinical forms have been delineated into 3 subtypes. Subtypes 1 and 2 have early onset, at birth or during the patient’s first 4 years of life. Both produce severe clinical features. Subtype 3 has late onset, frequently in patients older than 4 years, and patients develop milder symptoms.
The underlying defect in the disorder is a molecular defect that leads to a deficiency in the enzyme b-glucuronidase. b-Glucuronidase is required for the breakdown of dermatan sulfate (DS), heparan sulfate (HS), and chondroitin sulfate (CS). Accumulation of DS, HS, and CS takes place in many systems and tissues, including the central nervous system. An increase in the urinary excretion of HS, DS, and/or CS occurs. The exact pattern may vary considerably based on the subtype of MPS VII involved.
Frequency:
Mortality/Morbidity: Only a small sample of cases is available from which to extrapolate mortality figures for MPS VII. Fetal deaths have been noted several times. In mild cases, survival to age 19-20 years has been reported. Upper respiratory tract infections, neurodegenerative complications, and gastrointestinal tract conditions may contribute to reduced survival rates.
Sex: Males and females are affected in equal numbers.
Age: In severe forms, defects may appear prenatally, and in other forms, defects may be present at birth or during the first 2 of years of life. In the milder forms, clinical features may not be evident until age 4 years or later. As a point of emphasis, Sly syndrome is one of the few MPSs and lysosomal storage diseases that may be clinically evident at birth.
| CLINICAL | Section 3 of 10 |
History:
Physical:
Causes:
| DIFFERENTIALS | Section 4 of 10 |
Mucopolysaccharidosis Type IH
Mucopolysaccharidosis Type II
Other Problems to be Considered:
Mucolipidoses
| WORKUP | Section 5 of 10 |
Lab Studies:
Imaging Studies:
| TREATMENT | Section 6 of 10 |
Medical Care: No treatment is available for the underlying disorder, and care must be supportive. As a result of the variety of symptoms, a multidisciplinary approach to care may be appropriate. Possible Consultations are discussed below.
Surgical Care:
Consultations:
| FOLLOW-UP | Section 7 of 10 |
Complications:
Prognosis:
Patient Education:
| MISCELLANEOUS | Section 8 of 10 |
Medical/Legal Pitfalls:
Special Concerns:
| TEST QUESTIONS | Section 9 of 10 |
CME Question 1: Which of the following presentations is seen in patients with severe mucopolysaccharidosis type VII (MPS VII)?
A: Dysostosis multiplex
B: Hepatosplenomegaly
C: Hydrops fetalis
D: Sly syndrome
E: Heparan sulfate excretion
The correct answer is C: Dysostosis multiplex and hepatosplenomegaly are symptoms associated with MPS VII. Sly syndrome is a synonym for MPS VII. Heparan sulfate is one of the components found in the urine of patients with MSP VII.
CME Question 2: Which of the following components appears in the urine of patients with mucopolysaccharidosis type VII (MPS VII)?
A: Heparan sulfate
B: Dermatan sulfate
C: Chondroitin sulfate
D: A and B only
E: A, B, and C
The correct answer is E: Urinary levels of the mucopolysaccharides dermatan sulfate, heparan sulfate, and/or chondroitin sulfate are increased in patients with MPS VII. In addition, levels of the enzyme b-glucuronidase may be assayed in cultured skin fibroblasts and in leukocytes. Prenatal diagnosis for the enzyme deficiency also may be made by enzymatically analyzing amniotic cells and chorionic villi cells.
Pearl Question 1 (T/F): The metabolic defect mucopolysaccharidosis type VII (MPS VII) affects males more often than females.
The correct answer is False: Since MPS VII is inherited as an autosomal recessive trait, it affects males and females with equal frequency.
Pearl Question 2 (T/F): People with mucopolysaccharidosis type VII (MPS VII) often have a normal lifespan.
The correct answer is False: Although MPS VII is rare, of the recorded cases, most patients died in infancy or when younger than 20 years.
Pearl Question 3 (T/F): Treatment is available for mucopolysaccharidosis type VII (MPS VII).
The correct answer is False: Treatment is supportive and involves symptomatic care.
Pearl Question 4 (T/F): Patients with mucopolysaccharidosis type VII are sensitive to anesthesia; therefore, caution must be taken when surgery is required.
The correct answer is True: Patients with mucopolysaccharidosis may have an unusual sensitivity to anesthesia. Take precautions prior to any surgery involving a patient who has even a mild form of mucopolysaccharidosis.
| BIBLIOGRAPHY | Section 10 of 10 |
| NOTE: |
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