Neuroacanthocytosis in Japan — Review of the Literature and Cases

Since the first case report of this disease in 1974, a total of 71 cases of probable chorea-acanthocytosis (ChAc) were collected in Japan up to the end of 2006. These reports were reviewed for their clinical features and to document research achievements in Japan in this field. Whilst the clinical phenotype of these patients was typical of ChAc, most of these cases were diagnosed clinically without molecular diagnosis, so the diagnosis of McLeod syndrome cannot be completely excluded.

The mean age of onset was 30.5 (range 18–42) years and the male:female ratio was 18:7. Involuntary movements consisting of oro-lingual-facial dyskinesias and choreiform limb movements were seen in over 90% of cases. Self-mutilation of the lower lip was also seen with the same incidence. Depression or absence of deep tendon reflexes was noted in almost all cases. Cognitive impairment with or without psychiatric symptoms was noted in 40% of cases. The degree of acanthocytosis of peripheral red blood cells varied from 6 to 80% (mean value 24%). Serum creatine phosphokinase activity was increased in 86%. Computed tomography of the brain revealed symmetrical atrophy of the caudate nuclei in almost all cases examined. Forty percent of patients had seizures. The mode of transmission was predominantly autosomal recessive, but four families have been reported with apparent dominant inheritance. Sural nerve biopsy showed evidence of chronic denervation with axonopathy. Grouped atrophy of muscle fibers was also reported, but recent studies suggest a primary disorder of the muscle membrane or muscle fibers as a cause of elevated creatine kinase. Post mortem examination of the brain revealed marked neuronal loss and gliosis affecting the caudate nucleus and pallidum. The cerebral cortex and substantia nigra seemed to be spared. 15 cases of McLeod syndrome were identified in Japan between 1994 and 2006.

Many scientific advances were made in Japan with respect to ChAc. The red cell membrane pathology was studied morphologically as well as biochemically. Abnormal conformation of the red cell membrane was found, with an increase of palmitic and docosahexaenoic acids and a decrease of stearic acid. A mutation in the gene coding for a protein designated “chorein” was found and reported in a Japanese family with autosomal recessive inheritance, and a new single heterozygous frame shift mutation was also found from a family with apparent autosomal dominant inheritance. In addition, a gene-targeted mouse model of ChAc was reported from our country. The future of research in the area of ChAc in Japan is very promising.