Elizete Aparecida Lomazi

Visceral myopathy: Clinical and molecular survey of a cohort of seven new patients and state of the art of overlapping phenotypes

Visceral motility dysfunction is a key feature of genetic disorders such as megacystis‐microcolon‐intestinal hypoperistalsis syndrome (MMIHS, MIM moved from 249210 to 155310), chronic intestinal pseudo‐obstruction (CIPO, MIM609629), and multisystemic smooth muscle dysfunction syndrome (MSMDS, MIM613834). The genetic bases of these conditions recently begun to be clarified with the identification of pathogenic variants in ACTG2, ACTA2, and MYH11 in individuals with visceral motility dysfunction. The MMIHS was associated with the heterozygous variant in ACTG2 and homozygous variant in MYH11, while the heterozygous variant in ACTA2 was observed in patients with MSMDS. In this study, we describe the clinical data as well as the molecular investigation of seven individuals with visceral myopathy phenotypes. Five patients presented with MMIHS, including two siblings from consanguineous parents, one had CIPO, and the other had MSMDS. In three individuals with MMIHS and in one with CIPO we identified heterozygous variant in ACTG2, one being a novel variant (c.584C>T—p.Thr195Ile). In the individual with MSMDS we identified a heterozygous variant in ACTA2. We performed the whole‐exome sequencing in one sibling with MMIHS and her parents; however, the pathogenic variant responsible for her phenotype could not be identified. These results reinforce the clinical and genetic heterogeneity of the visceral myopathies. Although many cases of MMIHS are associated with ACTG2 variants, we suggest that other genes, besides MYH11, could cause the MMIHS with autosomal recessive pattern.

Effect of 4’galactooligosaccharide on constipation symptoms

OBJECTIVE Fructooligosacharides and galactooligosacharides soften fecal bolus and increase frequency of depositions when added to infant formula. This study aimed to determine the effects of galactooligosaccharide in pediatric patients with chronic constipation. METHODS From 2010 to 2012, 20 constipated patients (4-16 years of age) attended to at a primary healthcare unit were enrolled in a double-blinded, placebo-controlled crossover trial. Eleven children ingested galactooligosaccharide (1.7 g) for 30 days, followed by a 15-day washout period, and a 30-day period of placebo (maltodextrin). Nine patients ingested maltodextrin for 30 days, followed by 15-day washout period, and galactooligosaccharide (1.7 g) for 30 days. Constipation symptoms were considered as primary outcomes: bowel movements/week, straining during defecation, and stool consistency. Outcome symptoms were ranked according to a numerical scale elaborated for this study. Data were recorded at baseline, and on days 15 and 30 of each 30-day crossover period. Repeated-measures analysis of variance (ANOVA) was used to analyze symptoms along time. RESULTS At baseline, there was no significant difference in symptoms severity between groups (p=0.45). Galactooligosaccharide ingestion was related to increase of the bowel movement frequency, p<0.0001; relief of defecation straining, p<0.0001; and decrease in stool consistency, p=0.0014, compared to placebo ingestion. Patients reported no side effects from galactooligosaccharide. CONCLUSION Galactooligosaccharide was effective at improving clinical symptoms in this group of constipated children.Objective Fructooligosacharides and galactooligosacharides soften fecal bolus and increase frequency of depositions when added to infant formula. This study aimed to determine the effects of galactooligosaccharide in pediatric patients with chronic constipation.

Nutritional supplementation assessment with whey proteins and TGF-β in patients with Crohn's disease

UNLABELLED Crohns disease (CD) is a chronic inflammatory disorder that primarily affects the intestines, resulting in breakage of the intestinal barrier, pathological inflammation and nutritional disorders that encompass from trace elements deficiency to severe malnutrition. Nutritional interventions either alone or associated to drug therapy may be effective to achieve and maintain inflammation remission. OBJECTIVE To evaluate usual food intake as quantitative and qualitatively, in CD patients; and describe the effect of a supplement containing whey proteins and TGF- on their body composition. PATIENTS AND METHODS Dietary intake was assessed considering 42 consecutive patients, followed in a tertiary center, and by using the 3-day food recall and food intake frequency questionnaire. Body composition was assessed previously and 8 weeks after supplementation with a diet containing whey proteins and TGF-β (N = 22). RESULTS AND DISCUSSION Considering carbohydrates and lipids, most patients had adequate dietary intake according recommendations. Protein, saturated fat, B12 vitamin and zinc intakes were higher than the recommended values. The dietary fiber, A, D, C and E vitamins, calcium, iron, folate, potassium and sodium intakes did not reach the recommended requirements in most patients. Patients supplemented with the whey protein and TGF-β dietary presented a positive increment in their lean body mass, when compared to non-supplemented group. CONCLUSION CD patients require nutritional orientation. Whey protein intake resulted in significant differences, such as improvement in Lean Body Mass and reduction in Fat percentage.

Gastric emptying of water in children with severe functional fecal retention

The objective of this study was to evaluate gastric emptying (GE) in pediatric patients with functional constipation. GE delay has been reported in adults with functional constipation. Gastric emptying studies were performed in 22 children with chronic constipation, fecal retention and fecal incontinence, while presenting fecal retention and after resuming regular bowel movements. Patients (18 boys, median age: 10 years; range: 7.2 to 12.7 years) were evaluated in a tertiary pediatric gastroenterology clinic. Gastric half-emptying time of water (reference range: 12 ± 3 min) was measured using a radionuclide technique immediately after first patient evaluation, when they presented fecal impaction (GE1), and when they achieved regular bowel movements (GE2), 12 ± 5 weeks after GE1. At study admission, 21 patients had reported dyspeptic symptoms, which were completely relieved after resuming regular bowel movements. Medians (and interquartile ranges) for GE1 and GE2 were not significantly different [27.0 (16) and 27.5 (21) min, respectively (P = 0.10)]. Delayed GE seems to be a common feature among children with chronic constipation and fecal retention. Resuming satisfactory bowel function and improvement in dyspeptic symptoms did not result in normalization of GE data.

Original articleEffect of 4′galactooligosaccharide on constipation symptomsEfeito do galactooligosacarídeo sobre os sintomas de constipação☆☆☆☆☆☆

OBJECTIVE Fructooligosacharides and galactooligosacharides soften fecal bolus and increase frequency of depositions when added to infant formula. This study aimed to determine the effects of galactooligosaccharide in pediatric patients with chronic constipation. METHODS From 2010 to 2012, 20 constipated patients (4-16 years of age) attended to at a primary healthcare unit were enrolled in a double-blinded, placebo-controlled crossover trial. Eleven children ingested galactooligosaccharide (1.7 g) for 30 days, followed by a 15-day washout period, and a 30-day period of placebo (maltodextrin). Nine patients ingested maltodextrin for 30 days, followed by 15-day washout period, and galactooligosaccharide (1.7 g) for 30 days. Constipation symptoms were considered as primary outcomes: bowel movements/week, straining during defecation, and stool consistency. Outcome symptoms were ranked according to a numerical scale elaborated for this study. Data were recorded at baseline, and on days 15 and 30 of each 30-day crossover period. Repeated-measures analysis of variance (ANOVA) was used to analyze symptoms along time. RESULTS At baseline, there was no significant difference in symptoms severity between groups (p=0.45). Galactooligosaccharide ingestion was related to increase of the bowel movement frequency, p<0.0001; relief of defecation straining, p<0.0001; and decrease in stool consistency, p=0.0014, compared to placebo ingestion. Patients reported no side effects from galactooligosaccharide. CONCLUSION Galactooligosaccharide was effective at improving clinical symptoms in this group of constipated children.Objective Fructooligosacharides and galactooligosacharides soften fecal bolus and increase frequency of depositions when added to infant formula. This study aimed to determine the effects of galactooligosaccharide in pediatric patients with chronic constipation.

Recurrent apparent life-threatening event as the first manifestation of congenital myasthenia

OBJECTIVE To alert pediatricians about the importance of a careful investigation on recurrent apparent life-threatening events. Reports of the association of these events with congenital myasthenic syndromes were not found. CASE DESCRIPTION A seven-month-old infant with recurrent apparent life-threatening events was admitted for investigation. During hospital stay, she presented cyanosis and respiratory failure, requiring mechanical ventilation for three days. After clinical improvement, hypotheses of gastroesophageal reflux and pulmonary aspiration were ruled out. The presence of eyelid ptosis, general hypotonia and weak crying led to the suspicion of congenital myasthenia, which was confirmed. Treatment with oral piridostigmine led to neurological and nutritional normalization, without any other apparent life-threatening event during the next three years. COMMENTS The careful etiological investigation of apparent life-threatening events may lead to rare diagnosis that requires specific treatments, such as congenital myasthenia.Objective: To alert pediatricians about the impor- tance of a careful investigation on recurrent apparent life-threatening events. Reports of the association of these events with congenital myasthenic syndromes were not found. Case description: A seven-month-old infant with re- current apparent life-threatening events was admitted for investigation. During hospital stay, she presented cyanosis and respiratory failure, requiring mechanical ventilation for three days. After clinical improvement, hypotheses of gastroesophageal reflux and pulmonary aspiration were ruled out. The presence of eyelid ptosis, general hypotonia and weak crying led to the suspicion of congenital myasthenia, which was confirmed. Treatment with oral piridostigmine led to neurological and nutritional normalization, without any other apparent life-threatening event during the next three years. Comments: The careful etiological investigation of apparent life-threatening events may lead to rare diagno- sis that requires specific treatments, such as congenital myasthenia.

A rare association of intussusception and celiac disease in a child

CONTEXT: Intussusception is a common cause of acute intestinal obstruction in the pediatric population and it is normally idiopathic. Rare cases of chronic intussusception require investigation with greater attention. CASE REPORT: We present a clinical case of a three-year-old boy with aqueous diarrhea, abdominal distension, vomiting and weight loss over a two-month period. During the investigation, abdominal ultrasound showed imaging of intussusception. The intraoperative findings showed the intussusception had resolved spontaneously. In further investigation, it was found that the diarrhea was malabsorptive and, after the patient underwent upper gastrointestinal endoscopy, a diagnosis of celiac disease was made. After a gluten-free diet was introduced, the patient showed complete remission of symptoms and regained weight, and normal growth was reestablished. CONCLUSION: If the clinical presentation of intussusception is unusual, etiological investigation should be undertaken. In this case report, celiac disease was the underlying cause.

Evento com aparente risco de morte recorrente como manifestação inicial de síndrome miastênica congênita

OBJECTIVE To alert pediatricians about the importance of a careful investigation on recurrent apparent life-threatening events. Reports of the association of these events with congenital myasthenic syndromes were not found. CASE DESCRIPTION A seven-month-old infant with recurrent apparent life-threatening events was admitted for investigation. During hospital stay, she presented cyanosis and respiratory failure, requiring mechanical ventilation for three days. After clinical improvement, hypotheses of gastroesophageal reflux and pulmonary aspiration were ruled out. The presence of eyelid ptosis, general hypotonia and weak crying led to the suspicion of congenital myasthenia, which was confirmed. Treatment with oral piridostigmine led to neurological and nutritional normalization, without any other apparent life-threatening event during the next three years. COMMENTS The careful etiological investigation of apparent life-threatening events may lead to rare diagnosis that requires specific treatments, such as congenital myasthenia.Objective: To alert pediatricians about the impor- tance of a careful investigation on recurrent apparent life-threatening events. Reports of the association of these events with congenital myasthenic syndromes were not found. Case description: A seven-month-old infant with re- current apparent life-threatening events was admitted for investigation. During hospital stay, she presented cyanosis and respiratory failure, requiring mechanical ventilation for three days. After clinical improvement, hypotheses of gastroesophageal reflux and pulmonary aspiration were ruled out. The presence of eyelid ptosis, general hypotonia and weak crying led to the suspicion of congenital myasthenia, which was confirmed. Treatment with oral piridostigmine led to neurological and nutritional normalization, without any other apparent life-threatening event during the next three years. Comments: The careful etiological investigation of apparent life-threatening events may lead to rare diagno- sis that requires specific treatments, such as congenital myasthenia.

Refractory functional constipation: clinical management or appendicostomy?

OBJECTIVE To compare the clinical evolution in patients with refractory functional constipation undergoing different therapeutic regimens: oral laxatives and antegrade enemas via appendicostomy or clinical treatment with oral laxatives and rectal enemas. METHODS Analysis of a series of 28 patients with a mean age of 7.9 years (2.4-11), followed-up in a tertiary outpatient clinic. Refractory functional constipation was defined as continuous retentive fecal incontinence after at least a 12-month period of consensus therapy. After the diagnosis of refractory condition, appendicostomy was proposed and performed in 17 patients. OUTCOMES (1) persistence of retentive fecal incontinence despite the use of enemas, (2) control of retentive fecal incontinence with enemas, and (3) control of retentive fecal incontinence, spontaneous evacuations, with no need for enemas. RESULTS Six and 12 months after the therapeutic option, control of retentive fecal incontinence was observed only in patients who underwent surgery, 11/17 and 14/17, p=0.001 and p=0.001, respectively. At 24 months, control of retentive fecal incontinence was also more frequent in operated patients: 13/17 versus 3/11 with clinical treatment, p=0.005. In the final evaluation, the median follow-up times were 2.6 and 3 years (operated vs. clinical treatment, p=0.40); one patient in each group was lost to follow-up and 9/16 operated patients had spontaneous bowel movements vs. 3/10 in the clinical treatment group, p=0.043. Surgical complications, totaling 42 episodes, were observed 14/17 patients. CONCLUSION Appendicostomy, although associated with a high frequency of complications, controlled retentive fecal incontinence earlier and more frequently than clinical treatment. The choice of one of the methods should be made by the family, after adequate information about the risks and benefits of each alternative.

Evaluation of growth and nutritional status in children and adolescents with extrahepatic portal vein obstruction and portal hypertension

Objective This study aims to evaluate dietary intake, nutritional status, and growth rate in children and adolescents with extrahepatic portal vein obstruction and portal hypertension.