Perinatal-lethal Gaucher disease presenting with blueberry muffin lesions.

"Blueberry muffin baby" is an expression applied to newborns displaying a generalized purpuric rash caused by dermal erythropoiesis. This presentation is typically associated with TORCH (toxoplasmosis, other, rubella, cytomegalovirus, and herpesvirus) complex infections. However, alternative diagnoses should be considered, including other infections, neoplastic diseases, congenital vascular lesions, and metabolic diseases. We report a case of perinatal-lethal-type Gaucher disease presenting with cholestasis, hepatosplenomegaly, persistent thrombocytopenia, and blueberry muffin-like skin lesions.

Pediatric Fatty Liver and Obesity: Not Always Justa Matter of Non-Alcoholic Fatty Liver Disease.

Obesity-related non-alcoholic fatty liver disease (NAFLD) represents the most common cause of pediatric liver disease due to overweight/obesity large-scale epidemics. In clinical practice, diagnosis is usually based on clinical features, blood tests, and liver imaging. Here, we underline the need to make a correct differential diagnosis for a number of genetic, metabolic, gastrointestinal, nutritional, endocrine, muscular, and systemic disorders, and for iatrogenic/viral/autoimmune hepatitis as well. This is all the more important for patients who are not in the NAFLD classical age range and for those for whom a satisfactory response of liver test abnormalities to weight loss after dietary counseling and physical activity measures cannot be obtained or verified due to poor compliance. A correct diagnosis may be life-saving, as some of these conditions which appear similar to NAFLD have a specific therapy. In this study, the characteristics of the main conditions which require consideration are summarized, and a practical diagnostic algorithm is discussed.

Levothyroxine requirement in congenital hypothyroidism: a 12-year longitudinal study.

The aim of the replacement therapy with levothyroxine in congenital hypothyroidism (CH) is to correct hypothyroidism and ensure normal growth and neuropsychological development. Few data are available about the appropriate dose during childhood and early adolescence; therefore, we performed a multicenter observational study in a large population of patients with CH to assess the required levothyroxine dose to obtain euthyroidism. We recruited 216 patients with permanent CH classified into three groups (agenesia, ectopia, and in situ gland) on the basis of the thyroid imaging. The levothyroxine dose was recorded at 6 and 12 months and then yearly until 12 years of age. The daily levothyroxine requirement progressively decreased during the follow-up, irrespective of etiology. It was significantly lower in patients with in situ gland than in patients with athyreosis during the entire study period and with ectopic gland from the age of 1 year. The levothyroxine requirement at 6 months of age was correlated with the requirement at each later time-point. The daily dose was modified less frequently in patients with in situ thyroid (36 %) than in patients with ectopic gland (41.4 %) or with athyreosis (43.6 %). Patients with in situ gland required a lower dose than the other two subgroups. The dose at 6 months seems predictive of the requirement until 12 years of age. Euthyroidism may be achieved in pre-school and in-school patients by 3-4 and 2-3 µg/kg/day (70-90 and 60-80 µg/m(2)/day) of levothyroxine, respectively.

APECED: A Paradigm of Complex Interactions between Genetic Background and Susceptibility Factors.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive disease, caused by mutations of a single gene named Autoimmune regulator gene (AIRE) which results in a failure of T-cell tolerance. Central tolerance takes place within the thymus and represents the mechanism by which potentially auto-reactive T-cells are eliminated through the negative selection process. The expression of tissue-specific antigens (TSAs) by medullary thymic epithelial cells (mTECs) in the thymus is a key process in the central tolerance and is driven by the protein encoded by AIRE gene, the transcription factor autoimmune regulator (AIRE). A failure in this process caused by AIRE mutations is thought to be responsible of the systemic autoimmune reactions of APECED. APECED is characterized by several autoimmune endocrine and non-endocrine manifestations and the phenotype is often complex. Although APECED is the paradigm of a monogenic autoimmune disorder, it is characterized by a wide variability of the clinical expression even between siblings with the same genotype, thus implying that additional mechanisms, other than the failure of Aire function, are involved in the pathogenesis of the disease. Unraveling open issues of the molecular basis of APECED, will help improve diagnosis, management, and therapeutical strategies of this complex disease.

Acute adrenal failure as the presenting feature of primary antiphospholipid syndrome in a child.

INTRODUCTION: Antiphospholipid syndrome (APS) is characterized by recurrent arterial and venous thrombosis and detection of antiphospholipid antibodies (aPLs). This syndrome may be associated with connective tissue disorders, or with malignancies, but it may also appear in isolated form (primary APS). We report on a pediatric patient presenting with acute adrenal failure as the first manifestation of primary APS. CASE REPORT: A previously healthy 11-year-old boy developed fever, abdominal pain, and vomiting. An abdominal computed tomography scan showed nodular lesions in the adrenal glands. He was referred to our Department and a diagnosis of APS and acute adrenal failure was considered, based on positive aPLs (IgG and IgM), elevated ACTH levels and low cortisol levels. Other features were anemia, thrombocytopenia, elevated inflammatory parameters, hypergammaglobulinemia, prolonged partial thromboplastin time, positive antinuclear, anticardiolipin, anti-platelet antibodies, with negative double-stranded DNA antibodies. Lupus anticoagulant and Coomb's tests were positive. MRI revealed a bilateral adrenal hemorrhage. A treatment with intravenous metylprednisolone, followed by oral prednisone and anticoagulant, was started, resulting in a progressive improvement. After 2 months he also showed hyponatremia and elevated renine levels, indicating a mineralcocorticoid deficiency, requiring fludrocortisones therapy. CONCLUSION: The development of acute adrenal failure from bilateral adrenal haemorrhage in the context of APS is a rare but life-threatening event that should be promptly recognized and treated. Moreover, this case emphasizes the importance of the assessment of aPLs in patients with acute adrenal failure in the context of an autoreaction.