An important aspect of treatment is the screening of potentially affected relatives for abnormalities of serum copper and ceruloplasmin; if any relative is found to have the disease, penicillamine should be given indefinitely to prevent the emergence of neurologic symptoms. A full explanation of the dangers of ceasing the medication must be given, and compliance may have to be monitored.
Hereditary Deficiency of Ceruloplasmin (Aceruloplasminemia, CP Mutation)
This is a rare illness, biochemically similar to Wilson disease, occurring in patients with a recessively inherited deficiency of ceruloplasmin; it is not simply a heterozygous form of Wilson disease (the mutation involves a different gene). Cirrhosis and Kayser-Fleischer rings are not features of the disease but diabetes is common and extrapyramidal signs may or may not arise. Rather than copper, iron is deposited in the brain and liver (see discussion by Logan). Those few cases that have been well studied, mainly Japanese, show mainly an ataxic disorder (Miyajima et al).
Noted briefly here and discussed more extensively in Chap. 42, is an idiopathic progressive posterior and lateral column myelopathy that closely simulates subacute combined degeneration of B12 deficiency. It is associated with low serum copper levels, usually idiopathic but sometimes caused by malabsorption or the intake of zinc as an over-the-counter supplement to prevent colds or to improve the senses of smell and taste; zinc inhibits absorption of copper from the gut.
Neurodegeneration With Brain Iron Accumulation (PKAN, Formerly, Hallervorden-Spatz Disease, PANK Mutation)
This disease, recently renamed because of ignoble associations of the eponymous Hallervorden and Spatz, is also known as pigmentary degeneration of the globus pallidus. It is inherited as an autosomal recessive trait and is caused by, in all classic cases, a defect in the gene encoding pantothenate kinase 2 (PANK2), usually in the form of a missense mutation. The onset of symptoms is in late childhood or early adolescence with slow progression over a period of 10 or more years. The early signs are highly variable but are predominantly motor, both corticospinal (spasticity, hyperreflexia, Babinski signs) and extrapyramidal (rigidity, dystonia, and choreoathetosis). General deterioration of intellect is conjoined. In individual cases, ataxia and myoclonus have appeared at some phase of the illness. The spasticity and rigidity are most prominent in the legs, but in some instances they begin in the bulbar muscles, interfering with speech and swallowing, as happens in Wilson disease. We have observed patients who, over a period of years, exhibited only dystonia of the tongue, blepharospasm, or arching of the back. The relationship of this restricted form to the complete syndrome remains unsettled. Eventually, the patient becomes almost completely inarticulate and unable to walk or use his or her arms. Hayflick and colleagues found that only one-third of patients with atypical forms of the disease have mutations of the PANK2 gene. Moreover, variant cases tended not to show the characteristic changes on MRI described below.