Electron-microscopy of Cherry Haemangioma in the Early Diagnosis of Fabry Disease

Abstract

Fabry disease (FD) is a chronically progressive, congenital metabolic disease. Deficiency of a-galactosidase A (a-gal A) results in the accumulation of glycosphingolipids in various types of cell. Most male patients with FD develop renal failure, cardiac and cerebrovascular disease, which are the major causes of morbidity and mortality, occurring in the fourth or fifth decade of life ( 1 ). Thus, it is important to diagnose and start to treat FD as promptly as possible (2). We describe here a patient with FD who presented with only a few red papules, pathologically consistent with cherry haemangioma. CASE REPORTA 27-year-old Japanese man presented with a few, solitary, 2-3-mm diameter, bright-red papules on the chest and left shoulder (Fig. lA). His mother, a 52-year-old Japanese woman, had been diagnosed with FD due to asymptomatic cardiomegaly detected during a regular medical check-up. This prompted her son also to undergo examination. A detailed medical history revealed that he had been aware of relatively mild numbness and tingling in his extremities, and oligohidrosis after strenuous exertion, since approximately 10 years of age. Histologically, the papules showed numerous moderately dilated vessels lined with flattened endothelial cells and pericytes in the subpapillary region, sparing the papillary dermis. The intervascular stroma showed homogenization ofthe collagen. The overlying epidermis was slightly thinned and there was no vessel invagination into the epidermis (Fig. IB). We could recognize neither vacuolations nortoluidine blue-stained deposits in the cytoplasm of endothelial cells or sweat gland cells. We then performed electron-microscopy of the papules, demonstrating uneven dense and lamellar deposits in the cytoplasm ofthe endothelial cells and pericytes (Fig. 2). This finding is characteristic of lysosomal storage diseases, such as FD. Laboratory tests gave the following results; plasma a-gal A activity, 0.2 nmol/h/ml (normal 6.0-10.8 nmol/h/ml); urinary GL-3, 7.06 mg/mgCr (normal < 0.26 mg/mgCr); urinary a-gal A protein, 11.2 ng/mgCr (normal >38.2 ng/mgCr). Finally, the patient was diagnosed with FD and has been receiving enzyme replacement therapy (agalsidase beta; 1 mg/kg) for nearly 3 years, given every other week, starting from 2 months after his initial consultation at our institution. To date, this therapy has prevented the disease from progressing and the patient has been able to carry out his normal activities of daily living. Fig. 1. (A) Clinical presentation: 2-miii diameter, solitary, red papule on the right ehest. (B) Histologically, red papule shows the features of eherTy haemangioma rather than those of angiokeratoma (haematoxylin-eosin staining X 100). fig. 2. Electron-dense cytoplasmic inclusion bodies within vaseularendothelia! cells and pericytes (lead hydroxide staining, original magnification x 4.000).

Dermatologic Aspects of Fabry Disease

“…The most characteristic localization is the bathing trunk area (gluteal, genital and periumbilical areas, lower abdomen, and upper part of the thighs; Figures 2-4). [23][24][25] Isolated lesions might also be found over the chest, hands and feet, axillae, extensor surface of the arms, elbows ( Figure 5), and along the spine (suggesting trauma might act as a trigger in some areas, the Köebner phenomenon). 1 There seems not to be a correlation between the severity of the disease and the extension of the AKs, the mutation, or the amount of residual enzyme.…”