Okuyama T 1 , Kosuga M 1 , Kakee N 1 , Hirakiyama A 1 , Fuji N 1 , Kida K 1 , Eto Y 2 1 Crin Lab Med, NCCHD, Tokyo, Japan 2 Jikei Univ School of Medicine, Tokyo, Japan Background: Wolman disease is an autosomal recessive disorder of breaking down cholesteryl esters and triglycerides, resulting in accumulation of fat in the several organs. Major clinical manifestations are hepatomegaly and liver dysfunction. Enzyme replacement therapy is now under development. Its effectiveness is controversial because it is unclear whether significant accumulation and organ dysfunction initiate in fetal period or not. We had opportunity to analyze fetal liver and kidney of Wolman disease. Case report: A 36 year-old woman had two babies diagnosed as Wolman disease based on clinical manifestations. Gene test showed that the proband is a homozygote of 890 insert G of acid lipase gene. Prenatal genetic diagnosis was performed and the fetus was diagnosed as affected and aborted at 16 gestational weeks. An autopsy was done. Results: Liver and kidney tissue were obtained from the fetus. Cholesterol, Cholesteryl esters and triglycerides were separated by thin-layer chromatography. Apparent cholesterol ester accumulation was detected in liver and kidney tissue. In the liver, accumulation of triglycerides and cholesterol was also observed, indicating the accumulation had already started in fetal period. Conclusion: These data suggest enzyme replacement therapy for Wolman disease may not be effective when it starts after birth. Background: Tartrate-resistant acid phosphatase (TRAP), a lysosomal enzyme expressed in osteoclasts and macrophages, is a marker for growth and bone turnover, macrophage activation, and hairy cell leukemia. Recently, biallelic mutations in APC5, the gene encoding TRAP, have been found in patients with spondyloenchondrodysplasia (SPENCD), cerebral calcifications, spasticity and autoimmunity1. Abolished TRAP activity in serum and loss of expressed protein in patients' cells was demonstrated. TRAP deficiency causes hyperphosphorylation of osteopontin, a bone matrix protein, which appears to be the key pathogenetic factor for autoimmune disease in these patients. Here we report clinical characteristics of one of these patients. Case Report: The 15-years-old female patient was born to healthy consanguineous Turkish parents. First clinical findings evolved during the second year of age when chronic thrombocytopenia, progressive gait disturbance, spasticity, leukoencephalopathy, SPENCD, growth retardation, proteinuria, and episodes of severe hemolytic anemia developed. Her karyotype was found to be 46, XXX. Recently, homozygosity for an APC5 mutation was detected1; both parents were heterozygous for this mutation. Conclusion: SPENCD with leukoencephalopathy and autoimmunologic symptoms such as lupus erythematosus, hemolytic anemia and thrombocytopenia is highly suggestive of TRAP deficiency and requires further investigations with enzymatic and molecular genetic analyses.