Clinical diagnosis is confirmed by the finding of increased phytanic acid in the blood of a patient with a chronic, mainly sensory neuropathy; the normal level is less than 0.3 mg/dL but in patients with this disease, it constitutes 5 to 30 percent of the total fatty acids of the serum lipids. Urinary phytanic acid concentration is also raised. Genetic testing reveals the mutation, which is in PHYH in 90 percent of cases and in PEX7 in the others.
Treatment Diets low in phytol may be beneficial but this is difficult to judge, because after an acute attack there is sometimes a natural remission. The claimed effects of plasma exchange have also been difficult to interpret. In some patients there is a very slow progression of the disease, and in others, a more rapid progression with death from cardiac complications.
Like the cases of mitochondrial disease with neuropathy reported by Tuck and McLeod, we have observed several in which the clinical picture was almost identical to that of Refsum disease, but elevations in phytanic acid were not present. Mild ichthyosis, sensorineural deafness, ataxia of mixed tabetic-cerebellar type, areflexia, and retinitis pigmentosa were the main findings, conforming to the NARP syndrome described in Chap. 36. None of our cases had a family history of a similar disorder. Sural nerve biopsy showed loss of large fibers. There was an identifiable mitochondrial disorder in most of the recently studied cases, as described in Chap. 36. It should be remarked that most mutations of mitochondrial DNA cause a myopathy with multisystem disease, but not a neuropathy. The onset of the disease is in childhood or adolescence with slow progression.
Abetalipoproteinemia (Bassen-Kornzweig Syndrome, MTTP Mutation) (See Also Chap. 36)
This rare autosomal recessive childhood disorder was described in Chap. 37 with the inherited metabolic disorders of the nervous system and commented upon with neuroacanthocytosis in Chap. 38, although there is no relationship between the 2 processes. It is mentioned here because the brunt of the neurologic disorder falls upon the peripheral nerves. Acanthocytosis of red blood cells is its identifying feature. The earliest neurologic finding is usually diminution or absence of tendon reflexes, detected as early as the second year of life. Later, when the child is first able to cooperate in sensory testing, a loss of vibratory and position sense is found in the legs. Cerebellar signs (ataxia of gait, trunk, and extremities; titubation of the head; and dysarthria), muscle weakness, ophthalmoparesis, Babinski signs, and loss of pain and temperature sense are the other characteristic neurologic abnormalities, in more or less this order of frequency. Developmental delay, usually mild, occurs in some patients. Irregular progression occurs over a few years, and many patients are unable to stand and walk by the time they reach adolescence.
Skeletal abnormalities include pes cavus and kyphoscoliosis, which are secondary to the early onset neuropathy. Constriction of the visual fields and ring scotomata are manifestations of the macular degeneration and retinitis pigmentosa in some cases. Cardiac enlargement and congestive failure are serious late complications.
Neuropathologic findings consist of demyelination of peripheral nerves and degeneration of nerve cells in the spinal gray matter and cerebellar cortex. Diagnosis is confirmed by the finding of red blood cell acanthocytes, low serum cholesterol, and β (low-density)-lipoproteins. The disease is caused by defects in a triglyceride transfer protein, as discussed in Chap. 36. A deficiency of vitamin E, as a result of malabsorption, may be a factor, and large doses of the vitamin should be tried as therapy.