Mapping of a gene for severe pediatric gastroesophageal reflux to chromosome 13q14.

CONTEXT: Gastroesophageal reflux (GER) has not previously been widely regarded as a hereditary disease. A few reports have suggested, however, that a genetic component may contribute to the incidence of GER, especially in its severe or chronic forms. OBJECTIVE: To identify a genetic locus that cosegregates with a severe pediatric GER phenotype in families with multiple affected members. DESIGN: A genome-wide scan of families affected by severe pediatric GER using polymorphic microsatellite markers spaced at an average of 8 centimorgans (cM), followed by haplotyping and by pairwise and multipoint linkage analyses. SETTING: General US community, with research performed in a university tertiary care hospital. SUBJECTS: Affected and unaffected family members from 5 families having multiple individuals affected by severe pediatric GER, identified through a patient support group. MAIN OUTCOME MEASURES: Determination of inheritance patterns and linkage of a genetic locus with the severe pediatric GER phenotype by logarithm-of-odds (lod) score analysis, considering a lod score of 3 or greater as evidence of linkage. RESULTS: In these families, severe pediatric GER followed an autosomal dominant hereditary pattern with high penetrance. A gene for severe pediatric GER was mapped to a 13-cM region on chromosome 13q between microsatellite markers D13S171 and D13S263. A maximum multifamily 2-point lod score of 5.58 and a maximum multifamily multipoint lod score of 7.15 were obtained for marker D13S1253 at map position 35 cM when presumptively affected persons were modeled as unknown (a maximum multipoint score of 4.88 was obtained when presumptively affected persons were modeled as unaffected). CONCLUSION: These data suggest that a gene for severe pediatric GER maps to chromosome 13q14. JAMA. 2000;284:325-334

Severe cow's milk induced colitis in an exclusively breast-fed neonate. Case report and clinical review of cow's milk allergy.

Cow's milk induced eosinophilic colitis presenting in the first week of life has been reported, but is very rare. The authors describe a 4-day-old female infant who presented with profuse rectal bleeding resulting in a hematocrit fall from 38% to 30% within 8 hr after hospital admission. Sigmoidoscopy revealed colonic mucosa that was red, edematous, and friable, with punctate hemorrhages. Rectal biopsy showed marked eosinophilic infiltration with multifocal hemorrhage. Further history indicated that while the infant had been exclusively breast-fed since birth, the nursing mother had been drinking 4-5 glasses of cow's milk per day since delivery. Prick puncture skin testing of the infant was positive for cow's milk protein. A serum radioallergosorbent test (RAST) for cow's milk protein was positive. The infant's serum IgE was 1.5 IU/ml. Rectal bleeding resolved when the patient was given a casein hydrolysate formula (Nutramigen, Mead Johnson Nutrition, Evansville, IN), and endoscopy one week later showed improvement, with only scattered areas of erythema, and no friability. We conclude that since the infant was exclusively breast-fed, the milk protein must have passed into the breast milk antigenically intact. Prenatal sensitization probably occurred. Cow's milk induced allergic colitis should be considered in the differential diagnosis of colitis in breast-fed neonates.

Percutaneous diagnostic and therapeutic interventional radiologic procedures in children: experience in 100 patients.

Diagnostic and therapeutic interventional radiologic procedures that provide many treatment options in adults are gaining acceptance in pediatric medicine. Diagnostic (69 patients) and therapeutic (31 patients) interventional experiences in 100 children are summarized, and the procedures of choice for various clinical problems are outlined. Procedures include percutaneous biopsy for benign and malignant diseases, transhepatic cholangiography and biliary drainage, genitourinary procedures (nephrostomy, stent placement, balloon dilation), aspiration of fluid for laboratory analysis, therapeutic drainage of abscesses and noninfected fluid collections, and percutaneous gastrostomy and gastroenterostomy. Diagnoses were accurate in 96% of cases, and therapeutic procedures were successful in 84% of patients, usually obviating operation. Complications occurred in six patients (6%); the most severe was hemoptysis causing respiratory distress. There was no procedure-related mortality. Interventional procedures have wide applications in pediatric patients.

Recent experience with a modified Sawaguchi procedure for biliary atresia.

The treatment of biliary atresia by variations of the original Kasai hepatoportoenterostomy has shown early success with good bile flow and the elimination of jaundice in 50% to 70% of cases in many series. Long-term follow-up in many of these patients shows continued problems with ascending cholangitis and progressive liver disease leading to death. Our recent experience with a modified Sawaguchi hepatoportoenterostomy is encouraging. Twelve patients were operated on before two months of age. All but one became jaundice free within 2 to 4 months and had biliary intestinal continuity reestablished within 3 to 6 months. These 11 patients have remained jaundice free with normal growth and development 1 to 8 years postoperatively. Two patients had one and two episodes of cholangitis, respectively. All have continued mild elevations of hepatocellular enzymes but no patient has obvious signs of liver failure. Serial liver biopsies have shown clearing of bile stasis and continued periportal fibrosis. Size and number of ductules in the excised biliary remnant did not correlate with clinical outcome. One patient remained jaundiced after hepatoportoenterostomy and reoperation, and eventually expired. In contrast, two patients operated at 4 and 9 months of age never drained bile and eventually died of bleeding varices and hepatic failure, respectively. The atypical success and relative lack of cholangitis in this series is not readily explained, but may be related to specific technical modifications of the original Sawaguchi procedure.

Detection of urea cycle enzymopathies in childhood.

Inborn errors of ureagenesis must be considered in the differential diagnosis of recurrent vomiting and lethargy in childhood. Elevations of liver enzyme levels are often present during these episodes and may lead to an erroneous diagnosis of hepatic encephalopathy. We studied two cases of urea cycle defects.