Inherited deficiency of myophosphorylase leads to glycogen storage disease type V (McArdle's disease). We performed mutation analysis in 9 patients of eight unrelated families from Germany with typical clinical presentation of myophosphorylase deficiency. Beside previously described mutations we identified four novel mutations in the myophosphorylase gene. Four patients were homozygous for a nonsense mutation Arg49Stop that has been reported to be the most common mutation in white patients. Two affected siblings were compound heterozygotes for a novel missense mutation Gly685Arg and the nonsense mutation Arg49Stop. One patient carried a novel nonsense mutation Arg575Stop and a previously identified missense mutation Gly204Ser. In another patient, we identified a novel missense mutation Gln665Glu and a single-base deletion delA in Lys753. One patient of Turkish ancestry carried a newly identified homozygous A-to-G transition (ATG to GTG) abolishing the translation initiation codon of the myophosphorylase gene. These results suggest that Arg49Stop also is the most common genetic error associated with myophosphorylase deficiency in the German population. Our findings further demonstrate molecular heterogeneity of myophosphorylase deficiency among the clinically homogeneous patients we studied.

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A 32-year-old female patient is described who suffered from common symptoms such as Raynaud's phenomenon and swollen fingers, high titers of antibodies to U1RNP, SLE-like findings, scleroderma-like findings and polymyositis-like findings. A diagnosis of mixed connective tissue disease (Sharp-syndrome) was established. In addition, the patient had antibodies against cardiolipin, thrombocytopenia, recurrent fetal loss and a history of deep venous thrombosis of her left leg which is typical for an antiphospholipid syndrome. The symptoms dry eyes and dry mouth pointed at secondary Sjögren's syndrome. The diagnosis of these disease entities and the therapeutic regimens are described and discussed.

The ophthalmologist is able to confirm the clinical diagnosis by demonstrating the telangiectasia. Due to the increased disposition to malignant neoplasms regular check-ups should be performed.