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Azathioprine is an immunosuppressant drug belonging to the class of thiopurines widely used in clinical therapy. Its immunosuppressive action is linked to the substantial action mechanism in the inhibition of the synthesis of nitrogenous bases purine carried out in T-lymphocyte. The level of such medication limit resides in side effects such as myelosuppression and the development of tumours. The occurrence of side effects is linked to the presence of genetic polymorphisms of Thiopurine methyltransferase (TPMT). To date, 40 allelic variants for TPMT have been detected. However, those responsible for the reduction of enzyme activity are three: *2, *3A, *3C. The presence of one of the three polymorphisms makes the enzyme susceptible to degradation at proteasome level, and exposes the patient to high levels of the active drug that increases the probability of an occurrence of its side effects. Therefore, the Food and Drug Administration imposed the execution of a genetic test of TPMT typing in order to determine if the drug therapy is appropriate to the metabolic characteristics of the patient. The study had the aim of identifying the prevalence of the three aforementioned polymorphisms related to TPMT in a sample population in Palermo, Italy, highlighting the differences related to the sex of the patient and highlighting the main phenotypes. The results showed prevalence in the population of the absence of polymorphism. Among the most frequent polymorphisms is the *3A (3%). A percentage of 1.5% was found for the polymorphism *3C. No polymorphism *2 was identified in the population analyzed.

Familial Mediterranean fever (FMF) is an Autoinflammatory syndrome that is common in children in Mediterranean countries. The real prevalence of FMF in Sicilian children is unknown and need a wide population study. Furthermore, there are no data on the real prevalence of the different mutations between FMF patients and the concordance and/or discordance in clinical and biochemical parameters between patients of different generations.

Gene TNFRSF1A mutation is linked to TRAPS, autosomal dominant Autoinflammatory Disease (AID) with recurrent attacks of fever (2-3 weeks long), abdominal pain, vomiting, serositis, arthralgia and/or arthritis, myalgia, fasciitis, rash. The disease starts precociously and amyloidosis is reported in the 25% of the patients. Patients carrying the mutation R92Q usually show a mild clinical phenotype, with an extreme interindividual variability. Arthralgia and serositis are frequently less severe, however oral ulcers and pharyngitis are recurrent. Objectives: We studied the clinical and biochemical impact of the mutation R92Q in our population and the treatment outcome in all the patients with clinical relevant symptoms.

Background: Isolated hypoaldosteronism is an autosomal recessive inherited disorder of terminal aldosterone synthesis, leading to selective aldosterone deficiency. Two different biochemical forms of this disease have been described, called aldosterone synthase deficiency or corticosterone methyl oxydase, types 1 and 2. In type 1, there is no aldosterone synthase activity and the 18 hydroxycorticosterone (18 OHB) level is low, whereas in type 2, a residual activity of aldosterone synthase persists and 18 OHB is overproduced. Objective and hypotheses: Isolated aldosterone synthase deficiency should be considered in neonates and infants with failure to thrive and salt wasting. Normal levels of plasma aldosterone compared with highly elevated levels of plasma renin indicate an impaired aldosterone biosynthesis and suggest the disorder. Case presentation: We report the case of an infant with severe neonatal hyponatremia, hyperpotassemia and growth failure. She was born at 38 weeks of gestational age, weight: 3650 g. At the age of 1 month she was admitted to a paediatric unit for severe dehydratation, vomiting and growth failure. She showed normal values of plasma aldosterone (85 pg/ml) associated with hyperreninemia (88.2 ng/ml per h), hyponatremia and hyperkalemia. Molecular genetic analysis supported the diagnosis revealing a homozygous mutation for a pathogenic c.554COT (p.T185I) mutation in exon 3 of the CYP11B2 Aldosterone synthase gene (8q22). Treatment with fludrocortisone and oral supplementation with sodium, resulted in correction of hyponatremia and hyperkalemia, and a transient catch-up growth. The unaffected mother was a heterozygous carrier of the T185I mutation as the sister, while the father was a heterozygous carrier of the same mutation with a severe clinical course at the neonatal period and a normal sodium balance without no further drug supplementation in adult age. However actually the girl is 1.7 years old and shows a severe failure to thrive (height: 70.3 cm; weight: 7.300 kg) with a low growth velocity (!K2 SDS). She shows a bone age delay (1 year) and low IGF1 levels (!K2 SDS for age). She underwent GH stimulation testing witch documented a GH deficiency after pharmacological induction (peak: 5.2 ng/ml). Conclusion: At our knowledge this is the first case report of a child with a CYP11B2 gene mutation associated with GH deficiency, a further support to growth failure.

The coexistence of mutations in more than one gene, linked to Autoinflammatory Diesases, can confuse and make difficult the diagnosis and management of these patients, especially in childhood, when the clinical history is still brief.

When normal development and growth of the calvarial sutures is disrupted, craniosynostosis (premature calvarial suture fusion) may result. Classical craniosynostosis syndromes are autosomal dominant traits and include Apert, Pfeiffer, Crouzon, Jackson-Weiss, and Saethre-Chotzen syndromes. In these conditions, there is premature fusion of skull bones leading to an abnormal head shape, ocular hypertelorism with proptosis, and midface hypoplasia. It is known that mutations in the fibroblast growth factor receptors 1, 2, and 3 cause craniosynostosis. We report on a child with a clinically diagnosed Pfeiffer syndrome that shows the missense point mutation Q289P in exon 8 of the FGFR2 gene. This is a mutation not previously described in the Pfeiffer syndrome but reported in the Crouzon, Jackson-Weiss, and Saethre-Chotzen syndromes. In this paper, we propose the concept that these disorders may represent one genetic condition with phenotypic variability.