(a rare familial disease, caused by end-organ insensitivity to parathyroid hormone with distinctive skeletal and developmental abnormalities), the diminution in ionized serum calcium induces not only tetany and seizures but also choreoathetosis. This last symptom is presumably a result of calcification of the basal ganglia, which occurs in about one-half of the patients but of unknown mechanism. Also, in some instances there are signs of a cerebellar lesion. Pseudopseudohypoparathyroidism is a disorder that imitates the bony abnormalities seen in pseudohypoparathyroidism but in which calcium metabolism is normal and there are no neurologic features.
Sly and colleagues described the familial occurrence (21 cases in 12 families) of calcification in the caudate and lenticular nuclei, thalami, and frontal lobe white matter in association with osteopetrosis (“marble bones”) and renal tubular acidosis. Clinically, there were multiple cranial nerve palsies—including optic atrophy as well as psychomotor delay and learning disabilities—but no extrapyramidal signs. The cranial nerve palsies, which are a result of bony encroachment in neural foramina, were much less severe than in the lethal form of osteopetrosis. The pattern of inheritance of this disease is autosomal recessive (rarely X-linked), and the basic abnormality was found to be a deficiency in carbonic anhydrase II in red blood corpuscles and probably in kidney and brain. Several types of disease have been associated with corresponding mutations, mostly in CLCN7.
We emphasize that acquired extrapyramidal disorders are much more common than metabolic ones. For example, athetosis may follow hypoxic encephalopathy of birth or follow kernicterus caused by Rh and ABO blood incompatibilities and erythroblastosis fetalis. The same is true of the Crigler-Najjar form of hereditary hyperbilirubinemia, in which kernicterus (with ataxia or athetosis) may rarely appear as late as childhood or adolescence, the defect being one of glucuronide-bilirubin conjugation. Later in life, the more common causes are medications, illicit drug use, focal cerebral lesions, hyperosmolar nonketotic state, antiphospholipid antibody syndrome, among many others discussed in Chap. 4. Furthermore, a number of other rare diseases, which can only be classified as heredofamilial degenerations, also figure in the differential diagnosis of choreoathetotic or dystonic syndromes and are discussed in Chap. 39. Torsion dystonia is the best-known example.
With regard to rarer metabolic causes, ceroid- lipofuscinosis of the Kufs type, GM1 gangliosidosis, late-onset metachromatic leukodystrophy, Niemann-Pick disease (type C), PKAN disease, chorea-acanthocytosis, and Wilson disease may present with a syndrome of which dystonia or athetosis is an important component. Usually, there are other elements in the clinical picture as well, so that the correct diagnosis is seldom in doubt for long. dal Canto and colleagues have described a variant of neuronal ceroid-lipofuscinosis in which a boy and girl of unrelated non-Jewish parents developed severe choreoathetosis and dystonia at 6 to 7 years of age. Intellectual deterioration, gait abnormality, and seizures were added clinical features. Cerebral biopsy showed intraneuronal inclusions consisting of curvilinear bodies. These observations support the notion of nosologic heterogeneity among the nonglycolipid neuronal storage disorders.