OOA (Old Order Amish)

Inheritance: autosomal recessive
Genes: SGCB

LGMD2E
Limb girdle muscular dystrophy

Muscle weakness
Heart disease
Myopathy
Creatine kinase
Cardiac disease

Limb-Girdle Muscular Dystrophy, Type 2E

Clinical Characteristics

General description (for patients):

The limb-girdle type of muscular dystrophy is among the more uncommon forms of progressive muscle disease.  This type has its onset in the first decade of life, at an average age of 8.5 years.  Progressive muscle weakness leads to wheelchair confinement usually by the second or third decade of life although one patient has remained mobile for 44 years.  Often marked progression of weakness follows an acute illness.  Facial muscles are less severely involved than in other types of muscular dystrophy and heart muscle involvement is also less common.  The latter is probably why patients with this disease can live relatively long lives; one patient lived 67 years.

Medical description:  

Type 2E limb-girdle muscular dystrophy is an early onset, progressive muscle disease and far more uncommon than the Duchenne type.  Evidence of weakness is usually noted by family members late in the first decade of life, although it is likely that careful clinical evaluation would find earlier evidence.  Suspected cases in known families should be checked for serum creatine phosphokinase and glutamic oxaloacetic transaminase enzymes which are markedly elevated in this disease, even before any apparent weakness.  Muscle biopsies can confirm the diagnosis with dystrophic changes early and fat cell infiltration in more advanced disease.  Facial muscles are relatively spared, relative to the limb-girdle musculature, and the cardiac muscle also seems to be less involved than in Duchenne’s, for example. Patients with type 2E thus often live far into adulthood even though they may become confined to a wheelchair by the 3rd or 4th decade.

Genetics:

This is an autosomal recessive condition resulting from a mutation  (461C>G) in the SGCB gene encoding beta-sarcoglycan located on chromosome 4 (4q12).  This is the first recessive disorder reported in the Amish in 1961 when it was found among seven families in Daviess County in southern Indiana.  Interestingly, limb-girdle muscular dystrophy also occurs with high frequency in the canton of Bern, Switzerland, where these families originated.  A curious disconnect is found in the fact that, in spite of close genealogical ties to the Amish of Northern Indiana, the limb-girdle muscular dystrophy found there is caused by an entirely different mutation on a different chromosome (#253600).

Treatment:

No known treatment is available.

Prognosis:

An active lifestyle is not possible in this disease much beyond the first decade.  Life expectancy with good supportive care is good, however, since many individuals live to adulthood and one patient lived into the seventh decade.

Ancillary treatments and support:

Activity should be encouraged although its role in slowing the disease is unknown.

Specialists and specialty centers:

Neurologist, Pediatrician, Physical Therapy.

References:

Jackson, C.E., and Carey, J.H.:  Progressive muscular dystrophy: autosomal recessive type.  Pediatrics 28: 77-84, 1961. PubMed ID: 13718465

Jackson, C.E., and Strehler, D.A.:  Limb-girdle muscular dystrophy: clinical manifestations and detection of preclinicial disease.  Pediatrics 41: 495-502, 1968.  PubMed ID: 5637795

Allamand, V., Broux, O., Bourg, N., Richard, I., Tischfield, J.A., Hodes, M.E., Conneally, P.M., Fardeau, M., Jackson, C.E., and Beckmann, J.S.:  Genetic heterogeneity of autosomal recessive limb-girdle muscular dystrophy in a genetic isolate (Amish) and evidence for a new locus.  Hum. Mol. Genet. 4: 459-463, 1995.  PubMed ID: 7795603

Resources:

Muscular Dystrophy Association

Associated Graphics