BACKGROUND Pathogenic variations in HSD11B2 gene triggers the apparent mineralocorticoid excess syndrome (AME). There is scarce information regarding the phenotypes of subjects carrying heterozygous pathogenic variants in HSD11B2 gene. We investigated if serum cortisol/cortisone (F/E) ratio and cortisone are useful for identifying partial 11βHSD2 deficiency in those heterozygous subjects. METHODS We studied two patients diagnosed with AME and their families carrying either D223N or R213C mutation. We also evaluated 32 healthy control subjects (13 children and 19 adults) to obtain normal references ranges for all measured variables. Case 1: A boy carrying D223N mutation in HSD11B2 gene and Case 2: A girl carrying R213C mutation. We assessed serum F/E ratio and cortisone by HPLC-MS/MS, aldosterone, plasma-renin-activity(PRA), electrolytes, and HSD11B2 genetic analyses. RESULTS The normal values (median [interquartile range]) in children for serum F/E and cortisone (µg/dl) were 2.56 [2.21–3.69] and 2.54 [2.35–2.88], and in adults were 4.42 [3.70–4.90] and 2.23 [1.92–2.57], respectively. Case 1 showed a very high serum F/E 28.8 and low cortisone 0.46 µg/dl. His mother and sister were normotensives and heterozygous for D223N mutation with high F/E (13.2 and 6.0, respectively) and low cortisone (2.0 and 2.2, respectively). Case 2 showed a very high serum F/E 175 and suppressed cortisone 0.11 µg/dl. Her parents and sister were heterozygous for the R213C mutation with normal phenotype, but high F/E and low cortisone. Heterozygous subjects showed normal aldosterone, PRA, but lower fractional excretion of sodium and urinary Na/K ratio than controls. CONCLUSION Serum F/E ratio and cortisone allow to identify partial 11βHSD2 deficiencies, as occurs in heterozygous subjects, who would be susceptible to develop arterial hypertension.
Acute liver failure in children. Experience of a liver transplant center Background: Acute liver failure (ALF) in childhood is defined as biochemical evidence of liver injury, absence of known chronic liver disease and coagulopathy not corrected by vitamin K administration, with INR greater than 1.5 if the patient has encephalopathy or greater than 2.0 if the patient does not have encephalopathy. Objective: Report the experience of a single liver transplant center (LT) in the treatment of 8 children with ALF and review the literature. Method: Retrospective review of clinical charts of patients with ALF. Results: The median age was 8 years-old (range 0-11), three females. Five patients underwent LT. Two patients died, one of them LT. The etiologies were 4 undetermined, 1 autoimmune, 1 Wilson Disease, 1 Parvovirus and 1 chronic graft rejection. All grafts were from cadaver donor, 3 of them reduced. Two out of five patients with encephalopathy grade III-IV died. The one year survival rate was 75%. Conclusions: Children with ALF should be treated in experienced centers with facilities for liver transplant. Transplantation should be offered only if the underlying disease is treatable by liver replacement and if transplant prognosis is better than that of the underlying disease.
Beckwith–Wiedemann syndrome (BWS) is characterized by overgrowth and increased risk of embryonic tumors. It results from alterations in genes controlled by imprinting centers H19DMR (Imprinting Center [IC] 1) and KvDMR (IC2). Strategies for diagnostic confirmation include methylation analysis and CDKN1C sequencing. We present a newborn with placentomegaly, hyperinsulinism and adrenal cytomegaly, but no typical external features of BWS. The patient had normal genetic studies in blood. However, adrenal and liver tissues showed hypermethylation of IC1 and hypomethylation of IC2. Microsatellite analysis confirmed mosaic paternal uniparental disomy. This study demonstrates the importance of analyzing additional tissues to reduce underdiagnosis of somatic mosaicism in BWS.
Use of Sirolimus in five pediatric patients undergoing solid organ transplantation Background: Sirolimus (SRL) is an immunosuppressive drug increasingly used in children undergoing solid organ transplantation. SRL does not cause glucose intolerance, hypertension, nephrotoxicity or neurotoxicity, offering significant potential advantages over calceneurin inhibitors (CNI). Aim: To report five children treated with SRL. Material and methods: A retrospective review of four children undergoing orthotopic liver transplantation (OLT) and one undergoing renal transplantation with recurrent acute rejection (RAR), chronic rejection (CR) or toxicity due to CNI, treated with SRL between June 2001 and November 2006. Results: As primary immunosuppressive therapy, all patients received 3 drugs: CNI (Tacrolimus (FK) or Cyclosporine), mycophenolate mofetil and steroids. Mean age at treatment with SRL was 98 months. Children undergoing OLT had a late introduction of SRL (mean time after OLT: 37 months), and mean follow-up was 24 months. In this group rescue indications of SRL were RAR in one, CR in one, thrombotic thrombocytopenic purpura (TTP) in one, food allergy in one and other CNI toxicity in three. Only one did not experience adverse events due to SRL, but no one required discontinuation of SRL. There were remissions of RAR, CR, TTP and food allergy. The patient with RT was switched from FK to SRL at day 18 th after RT, but he had severe neutropenia that led to discontinuation of SRL. Conclusions: SRL may be useful in pediatric solid organ transplant recipients suffering from RAR, CR, TTP, food allergy and CNI toxicity. Careful attention should be directed to detect side effects and avoid severe complications (
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