Wikrom Karnsakul

Congenital maltase-glucoamylase deficiency associated with lactase and sucrase deficiencies.

Background Multiple enzyme deficiencies have been reported in some cases of congenital glucoamylase, sucrase, or lactase deficiency. Here we describe such a case and the investigations that we have made to determine the cause of this deficiency. Methods and Results A 2.5 month-old infant, admitted with congenital lactase deficiency, failed to gain weight on a glucose oligomer formula (Nutramigen®). Jejunal mucosal biopsy at 4 and 12 months revealed normal histology with decreased maltase-glucoamylase, sucrase-isomaltase, and lactase-phlorizin hydrolase activities. Testing with a 13C-starch/breath 13CO2 loading test confirmed proximal starch malabsorption. Sequencing of maltase-glucoamylase cDNA revealed homozygosity for a nucleotide change (C1673T) in the infant, which causes an amino acid substitution (S542L) 12 amino acids after the N-terminal catalytic aspartic acid. The introduction of this mutation into “wildtype” N-terminus maltase-glucoamylase cDNA was not associated with obvious loss of maltase-glucoamylase enzyme activities when expressed in COS 1 cells and this amino-acid change was subsequently found in other people. Sequencing of the promoter region revealed no nucleotide changes. Maltase-glucoamylase, lactase, and sucrase-isomaltase were each normally synthesized and processed in organ culture. Conclusions The lack of evidence for a causal nucleotide change in the maltase-glucoamylase gene in this patient, and the concomitant low levels of lactase and sucrase activity, suggest that the depletion of mucosal maltase-glucoamylase activity and starch digestion was caused by shared, pleiotropic regulatory factors.

Food Refusal as an Unusual Presentation in a Toddler With Duodenal Web

Duodenal web most commonly presents with a history of vomiting and failure to thrive in the early infancy period. This study reports on a child who had an initial presentation of feeding intolerance and rare nonbilious emesis. The unusual presentation of food refusal directed the investigation to an upper endoscopy to look for evidence of gastrointestinal mucosal disease such as gastroesophageal reflux disease, peptic ulcer disease, Helicobacter pylori infection, and food allergy including celiac disease. The finding of duodenal web with a central aperture was unexpected but explains the mild degree of her gastrointestinal symptoms.

Unusual case of hypothyroidism in an infant with hepatic hemangioma.

I nfantile hepatic hemangiomas (IHHs) are the most common tumors of infancy and occur in approximately 5% of children younger than age 1 year (1–4). Hemangiomas are postulated to arise from dysregulated angiogenesis (3,5), and vascular endothelial growth factor (VEGF) may play a role in the development of these tumors; thus, serum levels of VEGF can be used for diagnostic and therapeutic guidance (2). VEGF levels could be different in the proliferative versus involuting hemangiomas (6). A recently published study has shown that corticosteroids can suppress VEGF-A production by hemangioma-derived stem cells, thereby inhibiting vasculogenesis (7). Hepatic hemangioma can occur at all ages, diagnosed most commonly in individuals ages 30 to 50 years. Infants develop a type of hepatic hemangioma called benign hepatic hemangioendothelioma; these IHHs have also been detected prenatally in a growing fetus (8,9). IHHs are the most common benign neoplasm of hepatic vascular neoplasms of infancy; most are small and clinically silent. Symptomatic patients present in the first few months of age with a history of abdominal enlargement with or without other symptoms or signs related to their unique physiology. Extensive multifocal or diffuse hemangiomas may manifest as cardiac failure secondary to high-volume shunting, hypothyroidism, jaundice, and abdominal compartment syndrome. Hepatic failure is uncommon except after poorly performed embolization. Treatment of symptomatic IHH is aimed toward tumor suppression by the administration of corticosteroids, b-blockers, vincristine, and, in some instances, endovascular or surgical intervention. (10,11) Currently, first-line treatment consists of b-blocker (propranolol) therapy. Embolization may be required for severe high-output cardiac overload, only if pharmacotherapy is unsuccessful. Several groups have reported the development of an unusual form of consumptive hypothyroidism in infants with IHH (12–15). The hemangiomas in these infants express excessive amounts of type 3 iodothyronine 5-deiodinase (D3). This enzyme is considered an inactivating enzyme because it converts T4 and T3 to

Obesity and Reversed Growth Retardation in a Child with Type Ia Glycogen Storage Disease

ABSTRACT Type Ia Glycogen storage disease is an autosomal recessive hepatic metabolic disease due to a lack of glucose-6-phosphatase (G-6-Pase) activity presenting with growth retardation, lactic acidosis, fasting hypoglycemia with hypoinsulinemia, hyperuricemia, hepatomegaly, and hepatic adenoma with a risk of malignancy. The gene that encodes G-6-Pase was mapped to 17q21. There are some genotype-phenotype correlations. We report a case with delF327 mutation which is devoid of G-6-Pase activity; however clinical presentation in this case differs somewhat. Although correction of hypoglycemia and lactic acidosis with nocturnal intragastric feeding and uncooked starch therapy improves growth failure, mean height of the patients is often less than the target. Normal height and obesity in this case with hepatic steatosis and low hepatic glycogen storage requires clinical re-evaluation since there are some overlapping phenotypes between type Ia GSD and metabolic syndrome. The phenomenon may be related to insulin resistance as a consequence of early aggressive nutrition therapy with frequent low glycemic index meals.

Ascites in Children: A Single-Center Experience of 27 Years.

Objectives: The aim of our study was to describe the changing prevalence, demographic features, etiologies, and treatment of ascites in children hospitalized during a 27-year period at the Johns Hopkins Hospital (Baltimore, MD). Methods: We retrospectively reviewed discharges from 1983 to 2010 to select patients whose records included a diagnosis of ascites. We assessed the etiologies and degrees of ascites (ascites grade 1 detectable only by radiologic tests; ascites grades 2 and 3 recognized by moderate and marked abdominal distension by physical examinations). Results: We classified 518 children into 9 etiology groups: intrahepatic disease (IH) (105), hepatic vein outflow obstruction (HVOO) (45), congestive heart disease (CH) (33), nephrotic syndrome (NS) (36), pancreatitis (26), inflammatory and infectious diseases (77), malignancy (49), idiopathic (71), and miscellaneous (76). IH and CH were predominant in the younger age group (0–5 years) versus HVOO, pancreatitis, and malignancy in the older age group (13–21 years) (P < 0.001). The prevalence of ascites increased over time from 1983 to 2006 and declined thereafter. Ascites grade 1 was more common than ascites grades 2 and 3 in all the groups (P = 0.048). IH and NS were more likely to have ascites grade 2 and 3 (P = 0.02). Although spironolactone was more frequently used in the IH group versus other etiologies, furosemide was used more frequently in NS and CH versus other etiologies (P < 0.001). Conclusions: The increased prevalence of ascites during the initial study period could reflect improved detection radiologic detection. The proportion of severe ascites and the various medical treatments differed among the etiologic groups.

Idiopathic non-hypertrophic pyloric stenosis in an infant successfully treated via endoscopic approach

Non-peptic, non-hypertrophic pyloric stenosis has rarely been reported in pediatric literature. Endoscopic pyloric balloon dilation has been shown to be a safe procedure in treating gastric outlet obstruction in older children and adults. Partial gastric outlet obstruction (GOO) was diagnosed in an infant by history and confirmed by an upper gastrointestinal series (UGI). Abdominal ultrasonography and computed tomography scan excluded idiopathic hypertrophic pyloric stenosis, abdominal tumors, gastrointestinal and hepato-biliary-pancreatic anomalies. Endoscopic findings showed a pinhole-sized pylorus and did not indicate peptic ulcer disease, Helicobacter pylori infection, antral web, or evidence of allergic and inflammatory bowel diseases. Three sessions of a step-wise endoscopic pyloric balloon dilation were conducted under general anesthesia and a fluoroscopy at two week intervals using catheter balloons (Boston Scientific Microvasive(®), MA, USA) of increasing diameters. Repeat UGI after the first session revealed normal gastrointestinal transit and no intestinal obstruction. The patient tolerated solid food without any gastrointestinal symptoms since the first session. The endoscope was able to be passed through the pylorus after the last session. Although the etiology of GOO in this infant is unclear (proposed mechanisms are herein discussed), endoscopic pyloric balloon dilation was a safe procedure for treating this young infant with non-peptic, non-hypertrophic pyloric stenosis and should be considered as an initial approach before pyloroplasty in such presentations.

Exudative Hemorrhagic Duodenitis as a Primary Event in a Child With Henoch-Schönlein Purpura

2 4-year-old girl had a history of an acute onset of severe generalized colicky abdominal pain, fever, oral ulcer, loody diarrhea, and melena for 7 days. An examination showed ever, and generalized abdominal tenderness without organoegaly. Her blood tests showed a white blood cell count of 6,400/mL3, a hemoglobin level of 11.8 mg/dL, a hematocrit evel of 34.2%, a platelet count of 122,000/mm3, a neutrophil evel of 80%, an albumin level 2.6, a sedimentation rate of 11 m/h, and a C-reactive protein level of 6.5 mg/dL. A stool ulture, Clostridium difficile toxin, and parasites were negative. A agnetic resonance image of the abdomen showed significant owel-wall thickening in the duodenum and jejunum with dematous changes and sloughing of the mucosa (Figure A). A outine upper endoscopy revealed marked hyperemia, friability, nd edema with focal exudates in duodenum (Figure B). olonoscopy and ileoscopy were normal. The histologic findngs showed mild esophagitis, normal gastric mucosa, crypt bscess formation and cryptitis, fibrinopurulent exudates, an ncrease in mixed primarily neutrophilic inflammatory infilrates, and diffuse submucosal hemorrhage of the duodenum Figure C). The patient responded well with methylpredisolone within 1 week. Eighteen days after her onset of the llness a group of petechial rash appeared on her buttocks and he posterior aspect of her legs and progressed to significant urpura. Henoch-Schonlein purpura (HSP) was diagnosed.

ANTERIOR PITUITARY HORMONE EFFECTS ON HEPATIC FUNCTIONS IN INFANTS WITH CONGENITAL HYPOPITUITARISM

BACKGROUND Congenital hypopituitarism is an uncommon cause of neonatal cholestasis. Little is known about the effect of anterior pituitary hormone on hepatic functions. METHODS A retrospective review of the medical charts of eight infants with congenital hypopituitarism and neonatal cholestasis was performed. The results of endocrinological investigations, eye examinations, and magnetic resonance imaging were used to classify these infants. RESULTS Eight infants (4 male and 4 female; mean age, 1.7 weeks) who presented with cholestatic jaundice subsequently (mean age, 7.6 weeks) developed isolated or multiple anterior pituitary hormone deficiencies. Persistent hypoglycemia, ocular abnormalities, and microphallus were often clinical signs prompting further endocrinological and radiological investigations. Septo-optic dysplasia was prevalent, occurring in five cases. Cholestasis and hepatosplenomegaly resolved within a mean of 9.7 and 10 weeks, respectively, in the majority of cases after replacement of glucocorticoid and thyroid hormones. However, transaminase levels remained high after hormone replacement. Cortisol deficiency and hypoglycemia were noted in all cases, often following stress. Hyperlipidemia persisted in one case after the resolution of cholestasis and after corticosteroid and thyroid hormone replacement therapy. Growth hormone deficiency was not corrected due to the absence of hypoglycemia after corticosteroid hormone, an infants age, and/or a lack of financial resources. CONCLUSIONS In our series, it appears that glucocorticoid and thyroid hormones play a significant role in the resolution of cholestasis and hepatosplenomegaly. A persistently elevated transaminase level and hyperlipidemia after corticosteroid and thyroid hormone replacement may indicate the need for long-term follow-up and/or growth hormone therapy.

The Long Journey to Eradication of Hepatitis C Virus Infection Should Begin with the Smallest Victims

I n this volume of The Journal, Epstein et al 1 have made an important and timely contribution to our understanding of the need to improve hepatitis C virus (HCV) testing of pregnant women with opioid use disorder as well as their infants. The authors used electronic health records for a 10-year cohort of 879 women with opioid use disorder from an obstetric clinic serving women with substance use disorders. Only 85% of the women were screened for HCV. Of the 68% who were seropositive, only 72% had HCV RNA testing and 71% were viremic. There were 404 infants born to women who were HCV seropositive. Of these infants, 68% were tested at least once for HCV, but only 45% completed the American Academy of Pediatrics-recommended perinatal HCV screening. All 5 infants who were diagnosed with HCV infection were linked to care. The authors examined factors associated with maternal linkage to care; the more recent era of testing vs the earlier era was the only factor associated. Interestingly, maternal HIV coinfection and methadone maintenance therapy, compared with buprenorphine, were associated with improved infant HCV testing. The authors correctly concluded that HCV prevalence among pregnant women with opioid use is high, and infant HCV screening is imperfect. There were several limitations to the study, including the determination of genotype as a marker for future diagnostic testing. Another limitation was that there were 158 infants for whom there was no knowledge about foster care. It is astonishing that 28% of women who were seropositive did not undergo HCV RNA testing in the opioid use clinic. The authors focused on a variety of patient-related factors, although they did not mention maternal depression, which is known to be increased in mothers with HCV infection and they did not provide any information about the fathers. There was no information about the medical caregivers in the clinic (training? type of provider?) and the clinic policies on HCV testing of mothers and infants. There was no analysis at the provider level as to why a large proportion (28%) of women who were seropositive being cared for at the clinic were not tested for HCV RNA given the assumption that the medical caregivers were knowledgeable about HCV. Furthermore, there is no discussion of the clinic practice on conveying results of HCV testing of mothers to the medical caregivers for the infants. It has been estimated that there are approximately 11 million children who are HCV seropositive in the world, of whom 50% are viremic and in need of treatment. Most of these infants were infected via maternal fetal acquisition. Their data (see Figure 1 of the original report) is a poignant demonstration of the huge gap between infected women and the linkage of their infected progeny to care. Likewise, Delgado-Borrego et al reported that in Florida from 2000 through 2009, 2007 children were identified as having positive HCV antibody, only 12% of the expected number. Only 1.6% of the children who were HCV antibody positive were actively followed by a pediatric gastroenterologist in Miami-Dade County, Florida. She projected that, across the US, only 4.9% of the expected childhood cases have been identified. Given both the Epstein study and that of Delgado-Borrego, it is likely that the majority of the 5.5 million children in the world children with HCV have not been linked to care. The exciting advances in treatment of children with HCV infection with direct-acting antiviral agents make it even more important to link the infants to care. The results of the first pediatric trials of ledipasvir/sofosbuvir for genotype 1 and sofosbuvir/ribavirin for genotypes 2-3 have been published and these safe and highly effective therapies are now approved by the US Food and Drug Administration (FDA) for children 12 years of age and older. Studies are ongoing in 3to 12-yearold children. The only treatment that is currently FDAapproved for children 3-12 years of age is pegylated interferonribavirin, but this onerous therapy is generally no longer given, except for those young children with aggressive HCV-related liver disease. Furthermore the American Association for the Study of Liver Diseases/Infectious Diseases Society of American guidance suggested that all children with HCV infection in age groups for which direct-acting antiviral agents are approved should be treated. As the authors have noted, there are national goals of preventing new HCV infections, including elimination of mother-to-infant transmission, goals that are especially important given the opioid epidemic predominately affecting women of childbearing age. New strategies are needed to improve both maternal and infant linkage to care. The authors have suggested the possibility of combining infant care with maternal care. In theory, this strategy sounds ideal; however, we have previously reported our failure to achieve this goal. In our study, 125 subjects attending an opioid use clinic who were offered free HCV screening for their children as well as free hepatitis B virus vaccine made a follow-up appointment

Decision-making patterns in managing children with suspected biliary dyskinesia

AIM To explore and to analyze the patterns in decision-making by pediatric gastroenterologists in managing a child with a suspected diagnosis of functional gallbladder disorder (FGBD). METHODS The questionnaire survey included a case history with right upper quadrant pain and was sent to pediatric gastroenterologists worldwide via an internet list server called the PEDGI Bulletin Board. RESULTS Differences in decision-making among respondents in managing this case were observed at each level of investigations and management. Cholecystokinin-scintigraphy scan (CCK-CS) was the most common investigation followed by an endoscopy. A proton pump inhibitor was most commonly prescribed treating the condition. The majority of respondents considered a referral for a surgical evaluation when CCK-CS showed a decreased gallbladder ejection fraction (GBEF) value with biliary-type pain during CCK injection. CONCLUSION CCK infusion rate in CCK-CS-CS and GBEF cut-off limits were inconsistent throughout practices. The criteria for a referral to a surgeon were not uniform from one practitioner to another. A multidisciplinary team approach with pediatric gastroenterologists and surgeons is required guide the decision-making managing a child with suspected FGBD.