Spastic paraplegia associated with addison's disease: Adult variant of adreno-leukodystrophy

Abstract

Clinical and pathological features of an adult variant of adreno-leukodystrophy (ALD) are presented. A male with clinical and laboratory signs of Addison's disease (AD) developed at age 22 a slowly progressing paraplegia with slight sensory deficits in both legs and bladder and sphincter dysfunctions; he died at age 24 in an AD crisis. Autopsy revealed hyperplasia of lymphatic tissues, lymphocytic infiltrates in various organs including the CNS and adrenocortical atrophy with prominence of large ballooned, sometimes bizarre and occassionally striated cortical cells. CNS lesions consisted in incomplete demyelination of long tracts of brain stem and spinal cord with accentuation in the pyramical tracts; in these areas, perivascular cuffs of "epitheloid" histiocytic cells contained a strongly PAS-positive non-sudanophilic material. Electron microscopy demonstrated massive stroge of leaflet structures in perivascular histiocytes identical to the lamellar profiles previously described as specific for ALD. Some leaflets were found in close contact with compact lamellar arrays and with an electron-dense fingerprint material within astrocytes. In our case, the spastic paraplegia-AD syndrome which has been described previously in several clinical observations could be neuropathologically classified as an adult variant of ALD. Several differences to "classical" ALD occurring in young boys are stressed: the predominance of the endocrine disorder probably accounting for some of the perivascular lymphocyte infiltrates within the CNS; the absence of both clinical and pathological signs of diffuse cerebral involvement and the peculiar topistic pattern of CNS lesions and the very slow evolution of neurological signs paralleled by the absence of active sudanophilic demyelinating lesions. The possible mechanism of demyelination and the nature of the suggested metabolic defect in ALD are discussed. The ultrastructurally prominent leaflet structures may originate from myelin remnants, thus relating ALD to pathological storage of a myelin degradation product.

Signs of testicular insufficiency in adrenomyeloneuropathy and neurologically asymptomatic X‐linked adrenoleukodystrophy: a retrospective study

“…At least three patients (D, I and Z) reported that the characteristic sparse scalp hair had already manifested itself before puberty. In fact, in the very ®rst report of a patient with AMN, ®rst areolar, then diffuse alopecia was noted from the age of 8 years: a skin biopsy revealed chronic in¯ammatory in®ltrates in the corium (Budka et al, 1976). Additionally, the coexistence of X-ALD and autoimmune endocrine disease has been reported in several patients (Federico et al, 1988;Dumic et al, 1992).…”

Therapy of X-linked adrenoleukodystrophy

“…50 years later Powers and Schaumburg [1] demonstrated characteristic inclusions in adrenal cortical cells ( Fig 1C) and in brain macrophages, which were then identified as saturated very long chain fatty acids (VLCFA) by Igarashi et al [2]. This led to the recognition that X-ALD is a metabolic disease and the identification of thousands of new patients with the various clinical phenotypes by the detection of increased VLCFA plasma levels [3][4][5]. X-linkage of this disease was first proposed on basis of a pedigree analysis by Fanconi et al 1963 [6].…”

Postoperative adrenal crisis in an adolescent with Loeys-Dietz syndrome and undiagnosed adrenoleukodystrophy

“…Adrenomyeloneuropathy (AMN) is a milder form of the disease, which manifests itself most commonly in the late twenties with spastic paraperesis in the lower extremities, sphincter and sexual dysfunction, and adrenal dysfunction. 9,10 Finally, there is a form of the disease that manifests itself by only adrenal cortical dysfunction. Women who are heterozygotes of the disease can also develop AMN in adulthood.…”