Reduced levels of PANK2 in the blood corroborate the diagnosis but this test is available only in research laboratories with an interest in the disease. The characteristic deposits of iron in the basal ganglia have not been associated with a demonstrable abnormality of serum iron or of iron metabolism. It has, however, been reported that there is increased uptake of radioactive iron in the region of the basal ganglia following intravenous injection of labeled ferrous citrate (Vakili et al; Szanto and Gallyas). CT reveals hypodense zones in the lenticular nuclei, resembling those of hepatolenticular degeneration (also of sulfite oxidase deficiency, glutaric acidemia and Leigh disease), although high-density lesions have been described in one autopsy-proven case of this disease (Tennison et al). The MRI findings are striking (Fig. 36-8). In T2-weighted images, the rim of the pallidum appears intensely black (iron deposition), with a small white area in its medial part that represents a zone of necrosis (“eye-of-the-tiger” sign; see also Savoiardo et al).
The neuropathologic features prove to be the most distinctive attributes of the disease. There is an intense brown pigmentation of the globus pallidus, substantia nigra (especially the anteromedial parts), and red nucleus. Granules and larger amorphous deposits of iron mixed with calcium stud the walls of small blood vessels or lie free in the tissue. A loss of neurons and medullated fibers occurs in the most affected regions. Another unique feature is the presence of swollen axon fragments, which resemble those of neuroaxonal dystrophy. The significance of iron deposition is difficult to judge. To some extent, there is an increase of iron in the basal ganglia in other degenerative diseases. In Parkinson disease and striatonigral degeneration, for example, the deposition of iron is two to three times normal, presumably the result of degeneration of those tissues that are known to be rich in iron.
No treatment is known to be effective for the underlying disorder but treatment is available to ameliorate the dystonia and tremor. Some of our patients responded temporarily to l-dopa, but the effect was slight. The use of chelating agents to reduce iron storage has not helped.
This rare metabolic disease is inherited as an X-linked recessive trait. Although it carries the names of Lesch and Nyhan (see their 1964 description), the occurrence of uricemia in association with spasticity and choreoathetosis in early childhood had been described earlier by Cateland Schmidt. Essentially, it is a hereditary choreoathetosis with self-mutilation and hyperuricemia. The affected children appear normal at birth and usually develop on schedule up to 3 to 6 months of age. Maturational delay then sets in, initially with hypotonia that later gives way to hypertonia. Also, the patient’s behavior becomes abnormal, with aggressiveness and compulsive actions. The uncontrollable self-mutilation, mainly of the lips, occurs early (during the second and third year), and spasticity, choreoathetosis, and tremor come later. Most of the children learn to walk. Speech is delayed, and once attained, it is dysarthric and remains so throughout life. Mental retardation is moderately severe. In patients more than 10 years of age, gouty tophi appear on the ears, and there is increasing risk from gouty nephropathy. The serum levels of uric acid are in the range of 7 to 10 mg/dL.