There are many other conditions of metabolic type in which cerebellar ataxia figures in the clinical picture. Some of these are associated with polymyoclonus and cherry-red macular spots (mainly sialidosis or a-neuraminidase deficiency; see below). Cerebellar ataxia is a prominent feature of Unverricht-Lundborg (Baltic) disease and Lafora-body disease (see Chap. 15). The Cockayne syndrome and Marinesco-Sjögren disease persist into later childhood and adolescence or may even have their onset in this later period. In cerebrotendinous xanthomatosis (see further on), spastic weakness and pseudobulbar palsy are combined with cerebellar ataxia. Prader-Willi children have a broad-based gait and are clumsy in addition to being obese, genitally deficient, and diabetic. Several diseases associated with hyperuricemia implicate defective purine and pyrimidine metabolism and fit into this category; the enzymatic defect of Lesch-Nyhan disease is not present, however. Marsden and coworkers (1982) have observed cerebellar ataxia beginning in late childhood as an expression of adrenoleukodystrophy (see below). The familial syndrome of neuropathy, ataxia, and retinitis pigmentosa (NARP) caused by a mitochondrial genome mutation that impairs ATP synthase can cause ataxia and closely mimic the Marinesco-Sjögren syndrome.
Doubtless, many of the progressive forms of cerebellar ataxia now classified as degenerative and described in Chap. 38 will be proved to have an underlying biochemical or similar subcellular pathogenesis and will logically fall in place here, with the metabolic diseases. At present, when faced with a progressive ataxia of cerebellar type, even in a young adult, the reader should consult both this chapter and Chap. 38.
The acute forms of cerebellar ataxia that occur in late childhood and adolescence are essentially nonmetabolic, being traceable to postinfectious encephalomyelitis (see Chap. 35) or to postanoxic, postmeningitic, or posthyperthermic states and certain drug intoxications. With relatively pure cerebellar ataxias of this age period, postinfectious cerebellitis, cerebellar tumors (medulloblastomas, astrocytomas, hemangioblastomas, and ganglioneuromas of Lhermitte-Duclos) should be considered in the differential diagnosis. MRI establishes the correct diagnosis.
Bassen and Kornzweig, in 1950, first described this rare metabolic disease of lipoproteins that causes ataxia, sensory neuropathy, and acanthocytic deformity of red cells. It excited great interest, for it gave promise of a breakthrough into a hitherto obscure group of “degenerative” disorders. The inheritance is autosomal recessive and the mutation affects an apolipoportien transfer protein that impairs the ability to produce very low density lipoprotein (VLDL).
The initial symptoms, occurring between 6 and 12 years (range: 2 to 20 years), are weakness of the limbs with areflexia and ataxia of sensory (tabetic) type, to which a cerebellar component is added later (the first two aspects relating to a peripheral neuropathy are discussed in
Chap. 43). Steatorrhea, raising the suspicion of celiac disease (sprue), often precedes the appearance of a weak and unsteady gait. Later, in more than half the patients, vision may fail because of retinal degeneration (similar to retinitis pigmentosa). Kyphoscoliosis, pes cavus, and Babinski signs are other elements in the clinical picture. The neurologic disorder is relatively slowly progressive—by the second to third decade, the patient is usually bedridden.