Microdeletion 11q13.1.q13.2 in a patient presenting with developmental delay, facial dysmorphism, and esophageal atresia: possible role of the GSTP1 gene in esophagus malformation.

BACKGROUND: Esophageal atresia is a major congenital malformation characterized by a complete interruption of the esophageal continuity. It is frequently observed in associations and syndromes. As an isolated finding, it has a multifactorial etiology whose genetic factors are poorly known. Recently, the GST family, especially the GSTM1 null genotype (but not the GSTP1 polymorphism I105V), has been associated with esophageal atresia. These enzymes play a role in phase II detoxification of xenobiotics. Here we present the clinical and molecular findings observed in a patient suggesting that the loss of the GSTP1 allele might predispose to this malformation. CASE: We describe a patient presenting with esophageal atresia associated with developmental delay and facial dysmorphism, whose mother used tobacco and alcohol during the first 2 months of her pregnancy. Microdeletion/microduplication analysis was performed using comparative genomic hybridization and a 180K Agilent array. It detected a de novo 2 Mb chromosome 11q13.1.q13.2 deletion. CONCLUSION: The deleted chromosomal segment includes the GSTP1 gene. We hypothesize that the deletion of one GSTP1 allele (an isoform highly expressed in embryonic tissues), associated with specific environmental factors, such as tobacco and alcohol, could cause the esophageal atresia observed in our patient.

Oxidative stress and antioxidant enzyme activities in newborns with oesophageal atresia and their mothers.

OBJECTIVE: To measure the oxidant/antioxidant status of newborn babies with oesophageal atresia and their mothers, compared with healthy control subjects. METHODS: This case-control study included 40 participants: 10 newborns with oesophageal atresia and their mothers, and 10 healthy newborns and their mothers. Whole blood malondialdehyde (MDA) levels and the activities of antioxidant enzymes (catalase, carbonic anhydrase [CA], glucose-6-phosphate dehydrogenase [G-6-PD], and superoxide dismutase [SOD]) were measured. RESULTS: MDA levels and CA activity were significantly higher, and catalase, SOD and G-6-PD activities were significantly lower, in newborns with oesophageal atresia and their mothers than in healthy newborns and their mothers. Although CA activity was similar between the newborns and mothers in the patient group, it was significantly lower in newborns than in mothers in the healthy group. CONCLUSIONS: Increased lipid peroxidation might play an important role in the pathogenesis of oesophageal atresia. Impairment of the free radical/antioxidant balance may lead to increased free radical and decreased antioxidant levels in oesophageal atresia.

Long-term administration of prostaglandin E1: report of two cases with tetralogy of Fallot and esophageal atresia.

The authors continuously administered prostaglandin E1 (PGE1) iv to 2 infants with tetralogy of Fallot (TOF) and esophageal atresia with tracheoesophageal fistula (TEF) for more than 30 days, and observed side effects which could be attributed to the long-term administration of PGE1. After division of the TEF and anastomosis of the esophagus, leakage from the anastomosis developed in both cases. Because of the infectious foci in the thorax, Blalock's procedure was postponed and PGE1 was continued for 49 and 37 days. The authors believe radiographs of long bones and ribs demonstrated cortical hyperosteosis in both cases. Bone abnormalities became apparent approximately 30 days after the start of PGE1 and were associated with increases in serum alkaline phosphatase (peak value of about 2000 IU/L). Roentgenographic changes reverted toward normal and alkaline phosphatase values decreased after the cessation of PGE1 in both cases.

Congenital esophageal atresia: lipase activity is present in the esophageal pouch and stomach.

Lipolytic activity was studied in aspirates from the esophageal pouch and from the stomach of eight infants with congenital esophageal atresia. Lipolytic activity, tested with doubly labeled ([3H]glyceryl, [14C]fatty acid) long-chain triglyceride was present in esophageal and gastric aspirates. The activity in esophageal aspirates was in the range of 2.7-130 nmol/min/ml aspirate and that in gastric aspirates was in the range of 2.9-40.4 nmol/min/ml aspirate. The reaction products of lipolytic activity in esophageal and gastric aspirates were a mixture of mono- and diglycerides, glycerol, and free fatty acids. The lipolytic activity at the two sites--esophagus and stomach--varied with respect to pH optimum (5.0-7.6 and 6.0-6.5, respectively) and reaction products (glycerol 41.6 +/- 20% and 7.3 +/- 4.6%, respectively). These findings confirm the earlier observations that digestion of dietary fat is initiated in the stomach and suggest that the lipolytic activity present in gastric contents originates concomitantly from the oral-esophageal area as well as from the stomach. These studies do not exclude the possibility that the lipolytic activity in the stomach of infants with esophageal atresia could originate in regurgitated intestinal contents.

On the source of lipase activity in gastric contents.

--A convenient assay procedure for determination of the activity of pharyngeal lipase (gastric content lipase), using a long chain triglyceride as substrate, is described. Lipase activity in extracts of rat tongue, salivas collected from the upper esophageal pouch from two human newborns with congenital esophageal atresia and in gastric content obtained from an infant with pyloric stenosis were studied. Optimal lipase activities of the three enzyme sources were found in the same pH-range. During hydrolysis the composition of the products formed were also similar. The data presented indicate that at least some of the lipase activity which is responsible for lipolysis in the stomach of the newborn, originates in pregastric tissues.