MEN (General Swiss-German Mennonite)

Inheritance: autosomal recessive
Genes: GUSB

MPS VII
Sly syndrome
Beta-glucuronidase deficiency
GUSB deficiency

Hepatomegaly
Hydrops fetalis
Thoracolumbar gibbus
Prominent sternum
Mental retardation
Granulocyte inclusions

Mucopolysaccharidosis Type VII

Clinical Characteristics

General description (for patients): 

This is a metabolic disorder with a highly variable clinical picture.  Some live to adulthood whereas others develop severe disease in utero and may not live beyond birth.  The liver is often enlarged, some have skeletal deformities with short stature, a prominent sternum, abnormal curvature of the back and mental retardation can be present.  The facies appears ‘coarse’, the corneas may be cloudy, and the heart valves can be affected.

Medical description: 

MPS VII is among the more uncommon types of lysosomal storage diseases known as mucopolysaccharidoses.  The clinical picture is highly variable, ranging from lethal hydrops fetalis to mild clinical disease that may not be diagnosed until adolescence.  Granulocyte inclusions, hepatomegaly, variable degrees of mental deficiency, short stature, skeletal deformities (prominent sternum, gibbus), corneal clouding, heart valve defects, and coarse facies are common and result from a deficiency of β-glucuronidase which can be detected in fibroblast cultures.  It can also be detected prenatally in chorionic villus cells. 

Genetics:

A defect in the GUSB gene on chromosome 7 (7q21.11) is responsible for this disease.  Numerous mutations have been identified which may help explain the phenotypic heterogeneity.  Affected sibs of both sexes, parental consanguinity, and homozygosity of mutations suggest that this is an autosomal recessive disorder.  Homozygous GUSB mutations (526 C>T) have been identified in two Midwestern Mennonite sibs.  The parents were both heterozygous.

Treatment:

No effective treatment is available although allogeneic born marrow transplantation has been tried with mixed results.

Prognosis:

Highly variable.  Milder cases may live to adulthood but may die young probably secondary to cardiac arrest.

Ancillary treatments and support:

Depending upon the clinical picture, general supportive care may modify some symptoms.

Specialists and specialty centers:

Pediatrician, orthopedist, nutritionist, neurologist

References:

Wu ,B.M., Tomatsu, S.,  Fukuda, S.,  Sukegawa, K.,  Orii, T., Sly, W.S.:   Overexpression rescues the mutant phenotype of L176F mutation causing beta-glucuronidase deficiency mucopolysaccharidosis in two Mennonite siblings.  J. Biol. Chem. 269: 23681-23688, 1994.  PubMed  ID: 8089138

Vervoort, R., Islam, M.R., Sly, W.S., Zabot, M.-T. Kleijer, W.J., Chabas, A., Fensom, A., Young, E.P., Liebaers, I., and Lissens, W.:  Molecular analysis of patients with beta-glucuronidase deficiency presenting as hydrops fetalis or as early mucopolysaccharidosis VII.  Am. J. Hum. Genet. 58: 457-471, 1996.  PubMed  ID : 8644704

Tomatsu, S., Fukuda, S., Sukegawa, K., Ikedo, Y., Yamada, S., Yamada, Y., Sasaki, T., Okamoto, H., Kuwahara, T., Yamaguchi, S., Kiman, T., Shintaku, H., Isshiki, G., and Orii, T.:  Mucopolysaccharidosis VII: characterization of mutations and molecular heterogeneity.  Am. J. Hum. Genet. 48: 89-96, 1991. PubMed  ID : 1702266

Resources:

The National MPS Society

Associated Graphics