ARTHRITIS & RHEUMATISM Vol. 46, No. 7, July 2002, pp 1922–1925 DOI 10.1002/art.10391 © 2002, American College of Rheumatology Avascular Necrosis of the Femoral Head in a Patient With Fabry’s Disease Identification of Ceramide Trihexoside in the Bone by Delayed-Extraction Matrix-Assisted Laser Desorption Ionization–Time-of-Flight Mass Spectrometry Hiroshi Horiuchi, Naoto Saito, Seneki Kobayashi, Hiroyoshi Ota, Tamotsu Taketomi, and Kunio Takaoka Fabry’s disease is a lipid storage disease caused by an X-linked hereditary deficiency of -galactosidase. The enzymatic defect causes progressive deposition of ceramide trihexoside (CTH) in various tissues, leading to renal failure, premature myocardial infarction, and stroke, with a high rate of mortality in younger patients. Among the complications associated with Fabry’s dis- ease, a few cases involving avascular necrosis (AVN) of the femoral head have been reported. However, direct evidence of deposition of CTH in bone marrow in the femoral head has not been demonstrated. This report describes a 58-year-old man who underwent total hip arthroplasty for femoral head AVN associated with Fabry’s disease. The accumulation of CTH was exam- ined by chemical analysis of the sphingolipid extracted from the femoral head, using delayed-extraction matrix- assisted laser desorption ionization–time-of-flight mass spectrometry. This is the first report confirming the presence of CTH in the sphingolipid fraction from normal and necrotic bone of a patient with Fabry’s disease. Fabry’s disease is an inherited X-linked meta- bolic disorder of glycolipid catabolism caused by the -galactosidase enzyme (1). In this disease, globotriao- sylceramide, also called ceramide trihexoside (CTH), accumulates mainly in the heart, liver, kidney, vascular endothelial cells, and plasma. Common clinical manifes- tations of the disorder include angiokeratoma, as well as occlusive vascular disease of the heart, kidney, or brain (2,3). Of these complications, the most life-threatening is renal dysfunction. The diagnosis of Fabry’s disease may be made based on a low level of -galactosidase in the patient’s serum. Heterozygous female patients may present with an attenuated form of the disease. In a few cases, patients with Fabry’s disease have also presented with musculoskeletal involvement (4). A case of Fabry’s disease with avascular necrosis (AVN) of the femoral head and treatment with total hip arthroplasty is reported herein. Histologic analysis of the excised femoral head revealed AVN, with empty lacunae in the trabeculae, and conglomerate glycolipid-laden foamy macrophages in the bone marrow. The accumu- lation and distribution of CTH in the femoral head was examined by chemical analysis of the extracted sphingo- lipid, using delayed-extraction matrix-assisted laser de- sorption ionization–time-of-flight (DE–MALDI-TOF) mass spectrometry (5,6). To our knowledge, this is the first report confirming that sphingolipid fraction samples from normal and necrotic bones of a patient with Fabry’s disease contained CTH. CASE REPORT Clinical and laboratory findings. The patient, a 58-year-old man, presented to our hospital in January 1998 with pain in the left hip (of 1 year’s duration), gait Hiroshi Horiuchi, MD, Naoto Saito, MD, PhD, Seneki Koba- yashi, MD, PhD, Hiroyoshi Ota, MD, PhD, Tamotsu Taketomi, PhD, Kunio Takaoka, MD, PhD: Shinshu University, Matsumoto, Japan. Address correspondence and reprint requests to Naoto Saito, MD, PhD, Department of Orthopaedic Surgery, School of Medicine, Shinshu University, 3-1-1 Asahi Matsumoto, Japan. E-mail: Saitoko@hsp.md.shinshu-u.ac.jp. Submitted for publication January 11, 2002; accepted in revised form March 18, 2002. 1922