from were he wrote to the Minister of Education:"[...] From the last December to today, I've been under the influence of a malarial fever, with seven relapses and because of the advice of illustrious clinicians, among which Pietro Grocco, I took myself to this mountain where a modest benefit begins to be seen..." The desired improvement did not occur and Maffucci died in Pisa on November 24, 1903 at the age of 56. Research and discoveries Maffucci’s Syndrome In the Pisan period, Maffucci had the opportunity to conclude his studies on the disease he had discovered and since 1941, has been internationally known as “Maffucci's Syndrome”. It is a pathology that affects bones and skin at the same time and in which a benign cartilaginous tumor, called enchondroma, is associated with the appearance of cutaneous angiomas. Maffucci had described in 1881 the diseases for the first time, in a 40-year-old woman, hospitalized for a vascular tumor prone to severe and frequent bleeding, which died from complications resulting from amputation of the limb (site of the tumor). Signs and symptoms The signs and symptoms may be detected at birth, however they are more commonly seen at around 5 years of age. Enchondromas develop near the ends of bones, where normal growth occurs. Due to these bone malformations, people affected by Maffucci's Syndrome usually are short in stature and have underdeveloped muscles. Even though Maffucci's Syndrome starts out as benign, the tumors can become cancerous especially affecting the bones therefore the enchondromas may become chondrosarcomas. Causes Maffucci's Syndrome is generally caused by mutations in the IDH1 or IDH2 gene. These genes encode for enzymes called isocitrate dehydrogenase 1 and isocitrate dehydrogenase 2, respectively. These enzymes convert a compound called isocitrate to another compound called 2-ketoglutarate a reaction necessary to produce a molecule of the electron transport chain, NADPH, present in cellular respiration. Maffucci's Syndrome is not inherited as the mutations which cause it are somatic. The mutation is thought to occur in a cell during early development before birth; cells that arise from that abnormal cell have the mutation, while the body's other cells do not. This situation is called mosaicism. Tuberculosis The frequency and cruelty of tuberculosis disease at the end of the 800 will lead him to carry out the same experiments, his work goes so far that, in 1890 he communicates the discovery of two different tuberculous mycobacteria and,