HUT (Hutterite)

Inheritance: autosomal recessive
Genes: TRIM32

Muscular dystrophy Hutterite type
LGMD2H
Sarcotubular myopathy

Weakness
Creatine kinase deficiency
Fatigue
Myopathy
Limb girdle
Heart disease

Limb-Girdle Muscular Dystrophy, Type 2H

Clinical Characteristics

General description (for patients):

Childhood onset muscular weakness is often the first sign of this disorder, found only among Hutterites (in which another, more common type (#607155) is also present).  Weakness in the legs is the most prominent and often results in a waddling gait and difficulty in climbing stairs and standing up from a squatting position.  This condition is progressive and many patients become wheelchair-bound in the second and third decades.

Medical description:  

This is another form of limb-girdle muscular dystrophy found among the Hutterite populations. Clinical signs of lower limb and pelvic girdle weakness are often present by the age of six years, with slow progression to the need for assisted locomotion by the second and third decade. Unlike type 2I (see #607155), calf hypertrophy, cardiac symptoms and adverse reactions to general anesthesia are not seen in this condition.  Elevated serum creatine kinase levels are seen in both disorders.  Muscle histology and the EMG show evidence of a myopathy.

Genetics:

Like other LGMDs, this is an autosomal recessive disorder.  Type 2H results from a mutation (1459G>A) in the TRIM32 gene located on chromosome 9 (9q31-q24.1).  It has been found only in the Hutterite population in which mutations in FKRP causing type 2I cause a similar disease.  Interestingly, two Hutterite brothers with homozygosity of both the TRIM32 and FKRP mutations have been reported.

Treatment:

Physical therapy and exercise may be of benefit early.

Prognosis:

Poor. Most patients become wheelchair bound in the second and third decades.

Ancillary treatments and support:

General support.

Specialists and specialty centers:

Orthopedist, Physical Therapist, Pediatrician.

References:

Frosk, P., Del Bigio, M.R., Wrogemann, K., and Greenberg, C.R.:  Hutterite brothers both affected with two forms of limb girdle muscular dystrophy: LGMD2H and LGMD2I.  Europ. J. Med. Genet. 13: 978-982, 2005.  PubMed ID: 15886712

Frosk, P., Weiler, T., Nylen, E., Sudha, T., Greenberg, C. R., Morgan, K., Fujiwara, T. M., and Wrogemann, K.:  Limb-girdle muscular dystrophy type 2H associated with mutation in TRIM32, a putative E3-ubiquitin-ligase gene.  Am. J. Hum. Genet.70: 663-672, 2002.  PubMed ID: 11822024

Shokeir, M. H. K., and Rozdilsky, B.:  Muscular dystrophy in Saskatchewan Hutterites. Am. J. Med. Genet. 22: 487-493, 1985. PubMed ID: 4061485

Jerusalem, F., Engel, A. G., and Gomez, M. R. :  Sarcotubular myopathy.   Neurology 23: 897-906, 1973. PubMed ID : 4269389

Resources:

Muscular Dystrophy Association

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