Nonaka distal myopathy (described in Japan) and the quadriceps-sparing autosomal recessive inclusion body myopathy type 2 (IBM2; independently described in Iranian Jews and later in other Jewish and non-Jewish populations) constitute the same pathological entity, distinguished by the sparing of quadriceps. IBM2 prevalence in the Jewish population of Persian origin is 1/500. In Japan, prevalence of Nonaka myopathy is estimated to be 1 case per million inhabitants. Disease onset occurs between 20 and 30 years of age with weakness in the anterior distal legs, progressively leading to a steppage gait. Pelvic and femoral muscles are involved later in the disease course, but the quadriceps muscles are spared for a long time. The upper limbs (shoulders, wrist extensors, hands) are affected late in the disease course. Neck flexors may be weak. Facial and ocular muscles are also normally spared, along with cardiac and respiratory muscles. The disease progresses slowly, with disability appearing 10-20 years after the onset of the disease and patients often becoming wheelchair-bound by this stage. Serum creatine kinase levels are normal to slightly increased (2- to 5-fold). Nerve conduction velocities are normal. Muscular imaging (scanner or magnetic resonance imaging) is useful for detecting quadricep sparing. Muscular biopsy shows fibres containing rimmed vacuoles and congophile amyloid deposits. Inflammatory lesions have been reported in rare cases. Filamentous inclusions can be detected by electron microscopy in vacuolated fibres. The disease is transmitted in an autosomal dominant manner and has been linked to the locus 9p1-q1. Mutations have been identified in the GNE gene, which encodes an enzyme (UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase) involved in the sialic acid biosynthetic pathway. The mechanism of rimmed vacuole formation and their pathogenetic meaning still remain to be elucidated. Genetic counselling can be offered to families if the mutation is defined. In order to avoid articular deformation resulting from loss of muscular strength, personalised orthopaedic management is essential, including physiotherapy and fitting with prosthesis (a rigid splint and/or elastic strap helps to correct the steppage gait).
Last update: June 2006
- Dr Isabelle PENISSON-BESNIER