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Hematological features, often present at birth, are severe, transfusion-dependent, hypoplastic macrocytic anemia and a variable degree of neutropenia and thrombocytopenia associated to normal or reduced bone marrow (BM) cellularity with vacuolated precursors [Pearson et al., 1979; Stoddard et al., 1981]. Other features are exocrine and endocrine pancreas dysfunction, hyperlipidemia, liver steatosis, proximal tubular insufficiency, higher urinary excretion of lactate and organic acids, metabolic acidosis, failure to thrive, and skin lesions. Diagnosis is confirmed by Southern blot analysis which detects mtDNA rearrangements. No specific treatment is available so far and, therefore prognosis is unfavorable and death usually Bortezomib occurs in infancy or early childhood due to metabolic disorders and/or infections. Phenotype can shift from a predominantly hematopoietic disorder to a disease with muscle dysfunction with possible evolution to a full picture of Kearn�CSayre syndrome characterized by severe neurological symptoms [Casademont et al., 1994]. The severity of the clinical manifestations correlates with mtDNA gene mutation load and the distribution of mutation expression [R?tig et al., 1995; Jacobs et al., 2004]. We report on our experience with four patients with PS (Tables I�CII). A 11-month-old male, Dabigatran already reported [Solano et al., 2004], was admitted following a 2-month history of severe anemia. BM aspirate showed multinucleated erythroblasts, vacuolization of myeloid precursors, ring sideroblasts by Perls' stain, which led to the diagnosis of sideroblastic anemia. The patient received transfusions until age 4 when he showed a significant growth delay. Two years later, he developed impairment of the renal tubular function with metabolic acidosis. Southern blot analysis of mtDNA from fibroblasts revealed a deletion of 50% of the genome and click here PS was diagnosed. Two years later the patient developed adrenal insufficiency and, despite specific therapy, he died of sepsis. A 4-month-old female presented with macrocytic anemia [hemoglobin 6.8?g/dl, mean corpuscular volume 114?fl] and hyperlactacidemia (31?mg/dl; normal value