The diagnostic laboratory findings are spiky or thorny red blood cells (acanthocytes), low sedimentation rate, and a marked reduction in the serum of low-density lipoproteins (LDL cholesterol, phospholipid, and b- lipoprotein levels are all subnormal). The detection of the characteristic malformed red cells requires special handling of a wet preparation of blood diluted in isotonic saline and experienced microscopists. Despite the abnormal red cells, anemia is not found.
Pathologic study has revealed the presence of foamy, vacuolated epithelial cells in the intestinal mucosa (causing absorption block); diminished numbers of myelinated nerve fibers in sural nerve biopsies, depletion of Purkinje and granule cells in all parts of the cerebellum; loss of fibers in the posterior columns and spinocerebellar tracts; loss of anterior horn and retinal ganglion cells and of muscle fibers and fibrosis of the myocardium.
It has been proposed that the basic defect is an inability of the body to synthesize the proteins of cell membranes because of the impaired absorption of fat through the mucosa of the small intestine. Vitamin E deficiency, which is malabsorbed, may be a pathogenic factor, because the administration of a low-fat diet and high doses of vitamins A and E may prevent progression of the neurologic disorder according to Illingworth and colleagues, but the pathophysiology appears to be far more complex.
Often mentioned in the context of acanthocytosis is a related rare condition, McLeod syndrome, in which progressive muscular atrophy, seizures, involuntary movements, and elevated serum creatine kinase (CK) are combined in various configurations. The acanthocytosis in this disease is the result of an abnormality of the red cell surface Kell antigen (Kx, coding for the protein XK).
This is another rare but well-defined disease resembling abetalipoproteinemia, in which there is hypocholesterolemia, acanthocytosis of red blood corpuscles, retinitis pigmentosa, and a pallidal atrophy (HARP syndrome). Inheritance is autosomal dominant, and heterozygotes may exhibit some part of the syndrome. Many cases are caused by mutations in the gene encoding b-lipoprotein B. Fat droplets may be seen in the jejunal mucosa, indicating malabsorption. Cases have been reported from Europe, Asia, and the United States. Treatment consists of restriction of dietary fat and supplements of vitamin E. Several genes have been implicated.
An adult form of acanthocytosis unrelated to the above several diseases is associated with hereditary chorea and dystonia but evidence of lipid malabsorption is lacking. This disease is described in Chap. 38.
As stated in Chap. 4, the term myoclonus is applied to many conditions that are not at all alike but share a single clinical feature—a multitude of exceedingly brief, random, arrhythmic twitches of parts of muscles, entire muscles, or groups of muscles. Myoclonic jerks differ from chorea by virtue of their brevity (15 to 50 ms). Notably, both phenomena are considered to be symptomatic of “gray matter” diseases (“polioencephalopathies”).
Myoclonus or polymyoclonus may, in certain conditions, stand alone as a relatively pure syndrome. In most other cases, it is mixed with epilepsy or athetosis and dystonia, discussed further on. Most often, myoclonus is associated with cerebellar ataxia; thus it is being considered here, with the progressive cerebellar ataxias. The many acquired forms of polymyoclonus, such as subacute sclerosing panencephalitis, were mentioned in Chap. 4. This chapter is concerned only with those of known or presumed metabolic origin.