The tendon reflexes are abolished in nearly every case; rarely, they may be obtainable when the patient is examined early in the illness (see in the following text). Plantar reflexes are extensor and flexor spasms may occur even with complete absence of tendon reflexes (another manifestation of the spinal component). The abdominal reflexes are usually retained until late in the illness. Loss of vibratory and position sense is invariable from the beginning; later, there may be some diminution of tactile, pain, and temperature sensation as well. Sphincter control is usually preserved.
A notable feature in more than half of patients is a cardiomyopathy. The myocardial fibers are hypertrophic and may contain iron-reactive granules (Koeppen). Many of the patients die as a result of cardiac arrhythmia or congestive heart failure. For this reason, it is essential that affected individuals have a cardiologic assessment including electrocardiography and echocardiography. The cardiomyopathy of Friedreich disease can develop insidiously but with fulminant consequences. Kyphoscoliosis and restricted respiratory function are additional important contributory causes of death. Harding observed that approximately 10 percent of these patients have diabetes mellitus and a higher proportion have impaired glucose tolerance; there is both insulin deficiency and peripheral insulin resistance.
Variants of Friedreich ataxia In one important variant of Friedreich ataxia the tendon reflexes are preserved or even hyperactive and the limbs may be spastic. It is the finding of the aberrant frataxin gene that links these unusual cases to Friedreich ataxia; some are associated with hypogonadism. Harding (1981) found 20 such cases among her 200 familial ataxias at the National Hospital, London. Nevertheless, the distinction between classic Friedreich ataxia and ataxia with retained tendon reflexes is an important one clinically, insofar as kyphoscoliosis and heart disease do not occur in the latter group and the prognosis is better. Two of our Friedreich patients had occasional seizures. There are many additional forms of spinocerebellar ataxia, most displaying mainly a cerebellar atrophy, that may simulate Friedreich disease, but due to different mutations. These are taken up below.
Laboratory testing Laboratory tests of diagnostic value are the measurement of sensory nerve conduction velocities and amplitudes, which for the most part are normal because peripheral neuropathy is not a component of the process. Electrocardiography and echocardiography may demonstrate the heart block and ventricular hypertrophy. The CT and MRI seldom reveal a significant degree of cerebellar atrophy but the spinal cord is small. There is no consistent abnormality of blood or CSF and no biochemical abnormalities have been demonstrated. Genetic testing for the length of the GAA trinucleotide repeat segment in FXN is available.
Pathology The spinal cord is thin. The posterior columns and the corticospinal and spinocerebellar tracts are all depleted of myelinated fibers, and there is a mild gliosis that does not replace the bulk of the lost fibers. The nerve cells in the Clarke column and the large neurons of the dorsal root ganglia, especially lumbosacral ones, are reduced in number—but perhaps not to a degree that would fully explain the posterior column degeneration. The posterior roots are thin. Betz cells are also diminished in some cases, but the corticospinal tracts are relatively intact down to the medullary–cervical junction. Beyond this point, they are degenerated, but to a lesser degree than the posterior columns. The nuclei of cranial nerves VIII, X, and XII all exhibit a reduction of cells. Slight to moderate neuronal loss is seen also in the dentate nuclei, and the middle and superior cerebellar peduncles are reduced in size. Some depletion of Purkinje cells in the superior vermis and neurons in corresponding parts of the inferior olivary nuclei can be seen. Many of the myocardial muscle fibers degenerate and are replaced by fibrous connective tissue.