Later in the illness there is progressive impairment of renal function and cerebral and myocardial infarction. The characteristic dermal feature is the presence of numerous dark red macules and papules (angiokeratomas), up to 2 mm in diameter, over the trunk and limbs, most closely clustered over the thighs and lower trunk and around the umbilicus (angiokeratoma corporis diffusum). The comprehensive review by Brady and Schiffman is recommended. The responsible mutation has been identified in GLA.
Treatment Phenytoin, carbamazepine, gabapentin, or amitriptyline may be helpful in alleviating the pain and dysesthesias. As discussed in Chap. 36, enzyme replacement therapy has become available and seems to lead to partial remission of many of the features including the neuropathic ones.
Polyneuropathy of Acromegaly and Gigantism
Nerve entrapment, particularly of the median nerve, is a well-known feature of acromegaly. Pickett and colleagues identified carpal tunnel syndrome in 56 percent of acromegalics. Also recognized as a complication of acromegaly, but not because of multiple nerve entrapments, is polyneuropathy characterized by paresthesia, loss of tendon reflexes in the legs, and atrophy of slight degree in the distal leg muscles. Sometimes there are enlarged nerves. In the case reported by Stewart, the enlargement was the result of hypertrophic changes in the endoneurial and perineurial tissues, similar to those that occur in other so-called hypertrophic neuropathies of inflammatory or heredofamilial origin. In cases of extreme gigantism, a more severe polyneuropathy has sometimes been reported, to the point of causing Charcot joints (Daughaday).
Mentioned here is a case we have observed in which a severe and slowly progressive relatively symmetric motor neuropathy occurred in a patient with Pyle disease, a metaphyseal dysplasia that resembles acromegaly.
Metachromatic Leukodystrophy (ARSA Mutation, See Also Chap. 36)
In this metabolic disease, the congenital absence of the degradative enzyme sulfatase leads to massive accumulation of sulfatide throughout the central and peripheral nervous systems and to a lesser extent in other organs. The abnormality is transmitted as an autosomal recessive trait. Progressive cerebral deterioration is the most obvious clinical feature, but hyporeflexia, muscular atrophy, and diminished nerve conduction velocity reflect the presence of a neuropathy. Early in the course of the illness, the weakness, hypotonia, and areflexia may suggest Werdnig-Hoffmann disease; in older children there may be a complaint of paresthesias and demonstrable sensory loss. Bifacial weakness has been reported but must be rare. Sensory and motor conduction velocities are greatly slowed similarly in all nerves. Metachromatically staining granules accumulate in the cytoplasm of Schwann cells in nerves as well as in the cerebral white matter. There is loss of peripheral myelinated fibers. The measurement of arylsulfatase A activity in peripheral leukocytes or urine and biopsies of sural nerves are used to establish the diagnosis, even early in the course of the illness.
Inherited (Familial Amyloidosis, TTR Amyloidosis) Amyloid Neuropathies (See Table 43-6)