In Chapter 11, we reviewed Charcot–Marie–Tooth syndrome and related hereditary neuropathies. Here we discuss some of the more rare types of hereditary neuropathies (Table 12-1). Familial amyloid polyneuropathy is discussed in Chapter 16 (Neuropathies Associated with Systemic Disease).
TABLE 12-1.RARE HEREDITARY NEUROPATHIES
NEUROPATHIES ASSOCIATED WITH LYSOSOMAL STORAGE DISORDERS
The lysosomal storage disorders are associated with abnormal accumulation of lysosomal products (e.g., sphingolipids, mucolipids, etc.) within neurons, leading to dysmyelination and axonal degeneration of both central and peripheral nerves (Table 12-1). Usually, the central nervous system (CNS) manifestations overshadow the peripheral neuropathy in most of these disorders. However, some patients present with peripheral neuropathy, which can be associated with significant disability.
There are three characteristic forms of metachromatic leukodystrophy (MLD) defined by age of onset: (1) late infantile, (2) juvenile, and (3) adult onset.1–14 Most patients have the late infantile–onset MLD variant and develop progressive generalized weakness, decline in mental functions, dysarthria, and worsening gait between 1 and 2 years of age. Children become quadriparetic, spastic, and cortically blind and often develop seizures. On examination, generalized muscle weakness, hypotonia, hyporeflexia, and extensor plantar responses are appreciated. Most children die within 5–6 years after onset of symptoms.
The juvenile form of MLD typically presents later in childhood or adolescence but is associated with clinical features similar to the late infantile form of the disease. Patients with adult-onset MLD usually develop slowly progressive dementia, psychosis, spasticity, ataxia, extrapyramidal signs, visual impairment, and incontinence in the third or fourth decade of life.15
Magnetic resonance imaging (MRI) of the brain often demonstrates increased signal on T2-weighted images in the subcortical white matter (Fig. 12-1).
MRI of brain in a patient with MLD demonstrates widespread white matter disease on T2-weighted image. (Reproduced with permission from http://www.uiowa.edu/.)
The diagnosis is suggested by demonstrating decreased arylsulfatase A activity in urine, from leukocytes, or from cultured fibroblasts and can be confirmed with genetic testing. Prenatal diagnosis can be made by amniocentesis. Cerebral spinal fluid (CSF) protein is usually markedly elevated in the 100–300 mg/dL range. Motor nerve ...