Maria Cristina Schiaffino

Severe lactic acidosis due to thiamine deficiency in a patient with B-cell leukemia/lymphoma on total parenteral nutrition during high-dose methotrexate therapy.

An 11-month-old girl with B-cell leukemia/lymphoma developed profound lethargy due to severe lactic acidosis during chemotherapy and total parenteral nutrition (TPN). Initial treatment with NaHCO3 was ineffective. Treatment with a vitamin cocktail (OH-cobalamin, pyridoxine, thiamine, riboflavine, biotin, carnitine) at pharmacologic doses rapidly improved the childs clinical and laboratory status. Lactic acidosis was caused by an impairment of pyruvate dehydrogenase complex, which was due to lack of its necessary cofactor thiamine in the TPN. This case report indicates that lactic acidosis may be a front-line diagnosis in patients on TPN with lethargy and outlines the need for monitoring thiamine supply in TPN.

SMAD4 mutations causing Myhre syndrome result in disorganization of extracellular matrix improved by losartan

Myhre syndrome (MS, MIM 139210) is a connective tissue disorder that presents with short stature, short hands and feet, facial dysmorphic features, muscle hypertrophy, thickened skin, and deafness. Recurrent missense mutations in SMAD4 encoding for a transducer mediating transforming growth factor β (TGF-β) signaling are responsible for MS. We found that MS fibroblasts showed increased SMAD4 protein levels, impaired matrix deposition, and altered expression of genes encoding matrix metalloproteinases and related inhibitors. Increased TGF-β signaling and progression of aortic root dilation in Marfan syndrome can be prevented by the antihypertensive drug losartan, a TGF-β antagonists and angiotensin-II type 1 receptor blocker. Herein, we showed that losartan normalizes metalloproteinase and related inhibitor transcript levels and corrects the extracellular matrix deposition defect in fibroblasts from MS patients. The results of this study may pave the way toward therapeutic applications of losartan in MS.

A new SPINK5 mutation in a patient with Netherton syndrome: a case report.

Abstract:  We report on a case of Netherton syndrome showing a new SPINK5 mutation (c.957_960dupTGGT duplication in exon 11), associated with partial defect of biotinidase.

Laparoscopic Proximal Roux-en-Y Gastrojejunal Diversion in Children: Preliminary Experience from a Single Center

BACKGROUND Neurologically impaired children (NIC) have a high risk of recurrence of gastroesophageal reflux (GER) following fundoplication. A postpyloric feeding tube may be useful when gastric emptying disorders occur; however, dislocation and difficulty in feeding management often require more aggressive procedures. Total esophagogastric dissociation (Bianchis TEGD) is an alternative to the classic fundoplication procedure, whereas laparoscopic gastric bypass is a frequently performed procedure in morbid obesity, improving gastric outlet. AIM The aim of this paper is to present a preliminary experience on the laparoscopic Roux-en-Y gastrojejunal bypass, associated with Nissen fundoplication and gastrostomy, to treat and prevent GER in NIC with gastric emptying disorders. MATERIALS AND METHODS Eight neurologically impaired children underwent surgical treatment because of feeding problems and pulmonary complications. The procedure included: 1) hiatoplasty, 2) Nissen fundoplication, 3) 20-cm Roux-en-Y gastrojejunal anastomosis and jejuno-jejunal anastomosis, and 4) gastrostomy. RESULTS All cases were fed on postoperative day 3 without any intraoperative complications. One case developed an obstruction of the distal anastomosis due to adhesion and needed reoperation. Outcome was clinically evaluated with serial upper gastrointestinal contrast studies and endoscopies. CONCLUSIONS Laparoscopic proximal Roux-en-Y gastrojejunal diversion, without gastric resection, is a safe, feasible procedure that improves gastric emptying and reduces the risk of GER recurrence. Yet, long-term results still have to be evaluated.

A mild impairment of K+ATP channel function caused by two different ABCC8 defects in an Italian newborn

with frequent glucose-enriched meals or continuous intravenous high-rate glucose infusion to maintain normoglycemia [1]. In pancreatic β-cells, ATP-sensitive K+channel (K+ATP) regulates glucose-stimulated insulin secretion. K+ATP is composed by 4 ion channels (Kir6.2) and 4 regulatory sulphonylurea receptors (SUR1). They are also present in brain and in other neuroendocrine tissues [1]. Inactivating mutations in ABCC8 and KCNJ11, encoding, respectively, SUR1 and Kir6.2 subunits of the β-cell (K+ATP), are the most common causes [1]. Congenital hyperinsulinism can also be associated with mutations in the HNF4A gene, a cause of maturity onset diabetes of the young (MODY). A dual phenotype is observed in HNF4A-MODY with hyperinsulinemic hypoglycemia in the neonatal period progressing to diabetes in adulthood [2]. We present an infant carrying two ABCC8 mutations with a family history of hypoglycemia in infancy and diabetes mellitus in adulthood.