No abstract

Familial occurrence of inclusion body myositis is extremely rare, and only a few cases in Western countries have been reported. In these reports, a strong association of this disease with DR3 (DRB1*0301/0302) and the efficacy of immunosuppressants suggested that an immune pathomechanism is involved in the disease. We, for the first time, report two Japanese sisters who suffered myopathy clinicopathologically similar to inclusion body myositis. One sister received corticosteroid and azathioprine and the therapy relieved dysphagia. Both of our patients had DR15(2)/4 (DRBl*1502/0405), suggesting a distinct genetic association with the disease in the Japanese population.

No abstract

The optic-spinal form of multiple sclerosis (OSMS), characterized by recurrent involvement of optic nerve and spinal cord with rare brain magnetic resonance imaging lesions, is relatively common among Asians. While individual cases of OSMS with anti-thyroid autoantibodies (ATABs) have been reported, the frequency of ATAbs in OSMS and classical multiple sclerosis has not been studied. We studied serum ATAbs and anti-nuclear antibodies (ANA) in 46 Japanese patients with multiple sclerosis: 14 with OSMS, and 32 with non-OSMS. Six patients were positive for ATAbs: five women with OSMS and one man with non-OSMS. The frequency of ATAbs in OSMS (5/14) was significantly higher than that in non-OSMS (1/32; P = 0.007), but the frequency of ANA did not differ between OSMS (3/14) and non-OSMS (6/32; P = 0.99). There may be a pathogenetic link between anti-thyroid autoimmunity and a subgroup of OSMS in Japanese.

We report here a novel point mutation in exon 5 of the Cu/Zn superoxide dismutase (SOD) gene resulting in an amino acid substitution of valine(148) by isoleucine (V148I) in a Japanese family with amyotrophic lateral sclerosis (FALS). In this family, the age at onset was young (28.0 ± 3.8 years old, mean ± SD, n = 4) and the disease progression was rapid (22.0 ± 5.9 months, n = 3) with low Cu/Zn SOD activity (56.3 and 59.0% of the controls, n = 2). It is interesting that the clinical features of ALS varied very much among the affected members. One case had weakness of the lower extremities at first, and died without bulbar paresis. The second case first noticed wasting of the upper limbs with bulbar symptoms, but the third had weakness of upper extremities without developing dysarthria nor dysphagia until death. The living remainder first developed fasciculation of the tongue without weakness of extremities. The valine(148) is conserved among different species, and V148I mutation might destabilize dimer formation with another SOD subunit, leading to decrease enzymatic activity. These results suggested that there could be considerable clinical variance among the patients of FALS within one family, carrying the same Cu/Zn SOD mutation such as V148I.