Other Hereditary Motor and Sensory Neuropathies (Types III, IV, and X)

The cerebrospinal fluid (CSF) protein is often significantly increased. Nerve conduction studies may show absent sensory potentials and marked slowing of motor conduction velocity, with values in the range of 5 to 20 m/sec, characteristic of demyelinating process. Temporal dispersion and conduction block are not typically present. Nerve biopsy, which is usually not necessary for diagnosis, demonstrates a characteristic histologic picture of large onion bulbs (redundant Schwann cell processes from repetitive demyelination and attempts at remyelination) and very little intact myelin so that almost all of the axons are “naked.” In general, these nerve biopsies do not have inflammatory changes. Genetic testing for PMP22 and MPZ may show mutations.

HMSN IV is a rare condition. The clinical course of HMSN IV is severe and generally found earlier in life, sometimes in infancy and often with marked weakness. These patients have an autosomal recessive inheritance pattern. Nerve conduction studies typically, but not always, show a demyelinating pattern. These may be associated with other abnormalities aside from the length-dependent neuropathy, such as vocal cord paralysis or deafness. Several genes have been implicated in the development of HMSN type IV.

HMSN X, an X-linked dominant disorder, is much more common than types III and IV. HMSN X is usually more severe in males owing to the X-linked dominant inheritance. It usually becomes symptomatic in early adulthood. Nerve conduction studies show varying degrees of conduction slowing, with velocities intermediate between the ranges for demyelinating and axonal processes. Some reports indicate more severe electrophysiologic findings in males. Nerve biopsy shows predominantly axonal loss. Genetic testing for GJB1, the gene producing connexin-32, may be helpful diagnostically.

Refsum disease is a very rare autosomal recessive disorder characterized by abnormal fatty acid oxidation, leading to elevated levels of phytanic acid in the blood. Refsum disease usually begins in adolescence with a slowly evolving peripheral neuropathy, although it has a remitting-relapsing course in some patients. Most subjects have retinitis pigmentosa characterized by night blindness. Associated pupillary changes, nerve deafness, ataxia, cardiomyopathy, and ichthyosis may also be seen. In some patients, ataxia mimicking Friedreich ataxia is the initial complaint. Cerebrospinal fluid (CSF) findings and results of nerve conduction velocity studies are similar to those of Déjerine-Sottas disease. Although phytanic acid is a relatively ubiquitous compound found in many foods, a carefully controlled diet that excludes whole milk, all vegetables except potatoes, fat meats, chocolate, and nuts, can prevent further relapses and may improve the patient’s clinical condition.

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