Convulsive seizures may complicate nearly all hereditary metabolic diseases. The seizures may occur at all ages but more frequently in the neonate, infant, or young child than in the older child or adolescent. The seizures take many forms, as discussed in Chap. 15. Most often they are generalized grand mal or partial types; typical petit mal probably does not occur. Some diseases may cause focal seizures, simple or complex partial, before becoming generalized. The combination of series of polymyoclonic jerks progressing to a generalized motor seizure is always highly suggestive of one of the hereditary metabolic diseases. Another highly significant form of presentation is with sensory evoked seizures.
In the typical parkinsonian syndrome, with features of rigidity, tremor, and bradykinesia, strength remains relatively intact and corticospinal signs are absent, but effectiveness of movement is nonetheless impaired by the patient’s disinclination to use the affected parts (hypoor akinesia), by slowness (bradykinesia), and by rigidity and tremor (see Chap. 4). Other clinical syndromes in this category include choreoathetosis, dystonia, and spasms of gaze.
When the parkinsonian syndrome or some component thereof has its onset in middle or late adult life, it usually indicates idiopathic Parkinson disease or related multisystem forms. The development of such an extrapyramidal motor disorder in late childhood and adolescence instead suggests Wilson disease, juvenile Huntington disease, Hallervorden-Spatz disease, and the Segawa type of l-dopa–responsive dystonia as well as other so-called parkin mutations (see Chap. 38).
Hepatolenticular Degeneration (Wilson Disease, Westphal-Strümpell Pseudosclerosis, ATP7B Mutation)
Wilson’s description of “Progressive Lenticular Degeneration: A Familial Nervous Disease Associated with Cirrhosis of the Liver” appeared in 1912. A similar neurologic disorder had been described previously by Gowers (1906) under the title of “tetanoid chorea” and by Westphal (1883) and Strümpell (1898), as “pseudosclerosis.” None of these authors, however, recognized the association with cirrhosis. The clinical studies of Hall (1921) and the histopathologic studies of Spielmeyer (1920), who reexamined sections from the liver and brain of Westphal’s and
Strümpell’s cases, clearly established that the pseudosclerosis described by these authors was the same disease as the one that had been described by Wilson. Interestingly, none of these authors, including Wilson, noticed the golden-brown (Kayser-Fleischer) corneal ring, the one pathognomonic sign of the disease. Rumpell had demonstrated the greatly increased copper content of the liver and brain as early as 1913, but this discovery was generally ignored until Mandelbrote (1948) found, quite by chance, that the urinary excretion of copper was greatly increased in patients with Wilson disease and that it was increased even more after the intramuscular administration of the chelating agent British anti-Lewisite (BAL). In 1952, Scheinberg and Gitlin discovered that ceruloplasmin, the serum protein that binds copper, is reduced in this disease (see reviews by Scheinberg and Sternlieb for a full historical account and references). Denny-Brown demonstrated a recession of symptoms after prolonged treatment with BAL.