Postmortem diagnosis of Fabry disease with acromegaly and a unique vasculopathy

Abstract

A 44-year-old Japanese man with elevated growth hormone levels and gradual deterioration of mental and renal function was admitted to the hospital. With his deteriorated general condition and renal failure, the patient developed pulmonary thromboembolism and died of respiratory failure. Autopsy examination was conducted, which revealed abnormal accumulation or intracytoplasmic storage of lipid-rich material in the small blood vessels, kidney, heart, and nervous system. After postmortem pathologic studies, including light-microscopic histochemistry, electron microscopy, and biochemical analysis of the stored lipid contents, a final diagnosis of Fabry disease was made. Histopathologic examination revealed a unique vasculopathy characterized by the presence of abnormal intracytoplasmic lipid inclusions and vascular remodeling. With regard to the clinical presentation of acromegaly, hyperplasia but not adenomatous transformation of the acidophils of the anterior pituitary gland with immunohistochemical detection of growth hormone within the cells was noted. In this case, the complication of acromegaly with hyperplasia of the acidophilic cells of the anterior pituitary gland and the unique vasculopathy causing significant organ failure, mainly of the kidney, heart, and central nervous systems, possibly as a result of microcirculatory failure, are considered to be not incidental findings but to be intimately involved in the pathogenesis of Farby disease.

Autopsy case of the C12orf65 mutation in a patient with signs of mitochondrial dysfunction

“…After a thorough macroscopic inspection, conventional histologic techniques were performed to make specimens as mentioned previously. 5 – 7 Tissue sections were then stained with hematoxylin and eosin (H&E). At the time of autopsy, several small pieces of fresh brain tissue (right frontal lobe) were dissected, immediately frozen in dry ice, and stored at −80°C for future studies.…”

“…Electron microscopy was performed as previously reported. 7 Ultrathin sections were examined under a Hitachi H-7500 transmission electron microscope.…”

Unusual renal presentation of Fabry disease in a female patient

“…16 the acroparesthesias are partly caused by glycosphingolipid deposition in the vasa nervorum. 15 although the patient presented here exhibited no signs of cerebrovascular disease on brain magnetic resonance angio graphy imaging, and reported no prior angina pectoris, we feel that her presenting signs of an ischemic-kidney-like condi tion are hardly surprising, given the diffuse nature of arterial degenerative disorders. in fact, patients with Fabry disease have a generalized morphological and functional disorder of the arterial vessel tree, 17 and ischemic lesions have been reported at other atypical sites, including the hand.…”

“…in some patients, the vascular involvement can be severe enough to obscure the other classic symptoms of Fabry disease. 15,16 the cerebrovascular manifesta tions are primarily a result of multifocal small vessel involvement. 16 the acroparesthesias are partly caused by glycosphingolipid deposition in the vasa nervorum.…”

Vascular Aspects of Fabry Disease in Relation to Clinical Manifestations and Elevations in Plasma Globotriaosylsphingosine

“…[38][39][40] No atherosclerosis of significance was observed, confirming observations by others. 6,7,[41][42][43] Increased IMT was related some disease manifestations but lost significance when adjusted for age and sex. In general, an increase in IMT is associated with an increased risk of stroke.…”