Calpainopathy as differential diagnosis of idiopathic hyperCKemia

Background: The Calpainopathy (LGMD2A; OMIM 253600) is an autosomal-recessive bequeathed disease of the group of genetic determined limb-girdle muscular dystrophies. In 30% of the cases a mutation in the CAPN3-gen, which is encoded in the chromosomal region 15q15 and produces the proteolytic, cell mobility- and cell cycle- responsible enzyme Calpain-3, is the elicitor. The normal development of LGMD2A is comparatively consistent: very high levels of CK can be observed but nearly no muscular hypertrophies. Patients often don't need a wheelchair before 11 to 18 years after disease initiation and while rare cases of respiratory problems are reported, nearly no cardiac difficulties can be found.

Kasuistik: We report of an 11-year-old boy, who presented at the age of three years in the context of a regular blood examination elevated measures of transaminases (GOT 92U/l, GPT 99U/l) and of CK (1767U/l). No abnormal signs could be found in the clinical examination: no muscular hypertrophia, no contractures, no scapulae alatae, no organomegaly. A sonography of the heart and of the calves showed no pathology results. We also performed a muscular endurance testing in which the boy showed a CK-increase up to 1977U/l (96% CK- MM). Because of the persistency of the increased CK-measures, a muscle biopsy was realized and confirmed the suspicion of muscular dystrophy by presenting elevated levels of the Dystrophin-related-protein Utrophin. Utrophin is an indicator for sarkolemmal protein deficiencies. While the following moleculargenetic assais did not show Dystrophin-abnormalities, it was possible to verify the diagnose of compound heterozygosity in the exons: 04:c.550delA und 17:c.1981delA of the Calpain-3-gens.

In the meantime, nearly seven years after fixing the diagnosis the patient is still not complaining about muscular discomfort. Although a mild hypertrophy of the calves and a reduction of the achilles tendon can be seen; due to a regular physiotherapy these clinical findings do not constitute an impairment in quotidian live.

Conclusion: The Calpainopathy is a rare genetic determined limb-girdle muscular dystrophy, which can show a benign course when presenting in heterozygosity. Therefore a Calpainopathy should be excluded before considering a „idiopathic hyperCKemia“.