By way of exploring the anatomic basis of the clinical findings, pes cavus is not different from that seen in other neuromuscular diseases of early onset with mild hypertonus of the long extensors and flexors of the feet. There is also cause of amyotrophy of intrinsic foot muscles and foreshortening of the foot when the bones are still malleable. The kyphoscoliosis is probably a result of imbalance of the paravertebral muscles during development. The tabetic aspects of the disease are explained by the degeneration of large cells in the dorsal root ganglia and the large sensory fibers in nerves, dorsal roots, and the columns of Goll and Burdach. The loss of neurons in the sensory ganglia also causes abolition of tendon reflexes. Cerebellar ataxia is attributable to a combined degeneration of the superior vermis and the dentatorubral pathways but also the spinocerebellar tracts, in various combinations. Corticospinal lesions account for the weakness and Babinski signs and contribute to the pes cavus.
Diagnosis Friedreich disease and its variants must be distinguished from familial cerebellar cortical atrophy described next, and from familial spastic paraparesis with ataxia, as well as from peroneal muscular atrophy and the Levy-Roussy syndrome, which are discussed also with the hereditary neuropathies in Chap. 43. It is advisable to assay serum vitamin E levels, as a rare (except in North Africa) but treatable inherited deficiency of a vitamin E transport protein causes a spinocerebellar syndrome with areflexia in children that resembles Friedreich disease (see
Chap. 40). This rare recessive spinocerebellar ataxia associated with vitamin E deficiency arises from mutations in the gene that encodes an alpha tocopherol (vitamin E) transport protein. The absence of dysarthria and of skeletal or cardiac abnormalities in the vitamin-deficiency illness may be helpful. Exceptionally, a cardiac disturbance has been seen in the vitamin deficiency. A form of chronic inflammatory demyelinating polyneuropathy has long since overtaken tabes dorsalis as the most frequent type of areflexic ataxia. It bears a superficial resemblance to Friedreich ataxia when the onset is in early life, but lacks dysarthria and Babinski signs. A form of spinocerebellar degeneration related to human T-cell lymphotrophic virus type I (HTLV-I; Chap. 32), causing so-called tropical spastic paraparesis, as well as the vacuolar myelopathy of HIV multiple sclerosis, syringomyelia, neuroacanthocytosis, and cervical spondylosis, must be included in the differential diagnosis of late-onset cases. Genetic testing settles the matter.
Treatment Not much can be said on this subject because there is little effective therapy. A double-blind crossover study by Trouillas and associates found that the administration of oral 5-hydroxytryptophan modified the cerebellar symptoms. This has not been tested in another study. Apart from this form of treatment, with which we have had no experience, no therapeutic measures are known to alter the course of the disease. In several small trials, idebenone, an antioxidant (the short-chain analogue of coenzyme Q10), reduced the progression of left ventricular hypertrophy, a risk factor for arrhythmias and sudden death in these patients, but this could not be confirmed in subsequent trials. These results are summarized in an article by Filla and Moss. Heart failure, arrhythmias, and diabetes mellitus are treated by the usual medical measures and it bears repetition that careful evaluation of the cardiac disorder may prevent premature death. Surgery for scoliosis and foot deformities may be helpful in selected cases.