Original Paper Eur Neurol 2002;48:210–217 DOI: 10.1159/000066169 Peripheral Neuropathy of Machado-Joseph Disease in Taiwan: A Morphometric and Genetic Study Kon-Ping Lin Bing-Wen Soong Neurology, Neurological Institute, Taipei-Veterans General Hospital, and Department of Neurology, National Yang-Ming University School of Medicine, Taipei, Taiwan Received: January 1, 2002 Accepted: June 25, 2002 Kon-Ping Lin, MD Neurology, Neurological Institute, Taipei-Veterans General Hospital No. 201, Sec. 2, Shih-Pai Road Taipei 11217, Taiwan (ROC) Tel. +886 2 28757585, Fax +886 2 28757584, E-Mail kplin@vghtpe.gov.tw ABC Fax + 41 61 306 12 34 E-Mail karger@karger.ch www.karger.com © 2002 S. Karger AG, Basel 0014–3022/02/0484–0210$18.50/0 Accessible online at: www.karger.com/ene Key Words Machado-Joseph disease W Neuropathy W Morphometry Abstract Machado-Joseph disease (MJD) is a dominantly inher- ited cerebellar ataxia associated with spasticity, ophthal- moplegia, dystonia and peripheral neuropathy. Present- ed here are 5 MJD cases. A morphometric analysis of the histopathology of their sural nerves was carried out to know the relationship between axon size and myelin thickness. MJD cases were identified by polymerase chain reaction. On the basis of the clinical symptoms, there was 1 type I, 2 type II and 2 type III patients. The sural nerves were biopsied for single-fiber, ultrastructur- al and morphometric analysis. Morphometric parame- ters such as fiber and axon sizes, myelin thickness and g ratio (axon diameter:fiber diameter) were estimated. The pathological features of the sural nerves in the 2 type III and 1 of the type II patients revealed a loss of myelinated and unmyelinated fibers, and the morphometry studies showed a decreased fiber density, the loss of large myelinated fibers, a smaller size of the axons with thin- ner myelin sheaths and an increased percentage of my- elinated fibers with a g ratio (axon diameter:fiber diame- ter) above 0.7. However, only subtle pathological changes were noted in the type I patient and the remain- ing type II patient. Our findings suggested that there is a loss of large myelinated fibers and distal axonopathy with relative hypomyelination in the neuropathy of pa- tients with MJD. Copyright © 2002 S. Karger AG, Basel Introduction Machado-Joseph disease (MJD, MIM 109150) is char- acterized by cerebellar ataxia, pyramidal signs, progres- sive external ophthalmoplegia (PEO) and peripheral neu- ropathy. The MJD locus was first mapped to chromosome 14q13.1 in Japanese families [1] and the linkage was then confirmed in pedigrees from Portuguese families [2–4]. The MJD gene designed MJD has since been isolated and characterized. The mutation has been demonstrated to be an expansion of a trinucleotide CAG repeat that lies at the 3)-terminal of the coding region [5]. Pathologically, MJD is characterized by degeneration of the spinocerebellar tracts, dentate nuclei, pontine and vestibular nuclei, extrapyramidal structures (substantia nigra, locus ceruleus and the pallidoluysian complexes) as well as neuronal loss in motor cranial nerves, anterior horn cells and the posterior root ganglion [6, 7]. The cere- bral and cerebellar cortex and inferior olivae are not affected [1].