Juvenile Hemochromatosis in an Asymptomatic Patient-Importance of Early Diagnosis.

Juvenile hemochromatosis is a rare inherited disorder of iron regulation leading to iron overload, which usually presents before the age of 30. One of the most serious clinical characteristics associated with early-onset iron overload is liver disease with eventual cirrhosis, often associated with a reduced life expectancy even after treatment. This case report summarizes an asymptomatic pediatric patient with persistently elevated transaminase levels, which led to a diagnosis of juvenile hemochromatosis relatively early in the course of his disease. The aim of this case report is to increase awareness and stress the importance of early diagnosis and treatment, as it is vital to prevent life-threatening complications and optimize patient outcomes. Consideration should be taken to recognize potential manifestations despite the rarity of the condition. Patients with signs of hepatocellular injury without explanation should prompt evaluation including consideration for iron overload after other common causes are ruled out.

The Pattern of CT Scan Use in the Diagnosis of Abdominal Pain in Children Presenting to the Emergency Department of a Tertiary Community Hospital.

Background and objective Pediatric populations are highly sensitive to ionizing radiations and, therefore, are more at risk of their harmful outcomes. Our study aimed to determine the percentage of children who underwent a CT scan after presenting to the ED with abdominal pain. The secondary aim was to determine the change in management related to the CT results. In addition, we also wanted to determine the predictors associated with the use of abdominal CT scans in the evaluation of children presenting to ED with abdominal pain as well as the predictors associated with positive CT scan results in children with abdominal pain. Materials and methods We retrospectively reviewed the medical records of children with abdominal pain seen in our ED from 01/01/2011 through 12/30/2012. Patients aged 4-18 years presenting with abdominal pain were identified from the medical records. Data on demographics, clinical characteristics, associated factors, CT use, CT findings, and change in management were collected. Data were analyzed using Chi-square (χ2) analysis and Student's t-test. Results A total of 1,780 charts were reviewed and 1,272 children were included in the study. The mean age of the cohort was 12.6 ± 4.6 years; 62.6% were female and 68.7% were African American. Of note, 14% (181/1,272) of the study group had received a CT scan; change in medical management was noted in 34.8% (63/181) of the scanned patients. Predictors of CT use included older age (p<0.0001), male gender (p<0.0001), white race (p<0.0001), an attending without advanced training in pediatric emergencies (p=0.001), acute onset of symptoms (p<0.0001), higher pain score (p<0.0001), right lower quadrant pain (p<0.0001), abdominal wall rebound tenderness (p<0.0001), abdominal tenderness (p<0.0001), fever (p<0.0001), and absence of constipation (p=0.04). Positive CT scan results were predicted by the presence of fever (p=0.013), lack of constipation (p=0.025), and white race (p=0.022). A multivariate analysis could not be done because not all data were available for each patient. Conclusion The use of the CT scan in children with abdominal pain affected the management in one out of three patients (34.8%). Fever, constipation, and white race were the factors associated with an increased likelihood of performing a CT scan and were also linked to positive results.

Glycogen Storage Disease Type IX due to a Novel Mutation in PHKA2 Gene.

We report a case of a 17-month-old male with a history of developmental delay with poor muscle control, hepatomegaly, and transaminitis. Ultrasound of abdomen revealed hepatomegaly with a liver span of 13 cm, homogeneous parenchyma, and normal spleen size. Liver and muscle biopsies were obtained: the liver biopsy revealed distended hepatocytes with excessive glycogen accumulation and fine septate fibrosis. Biopsy of the right vastus lateralis muscle showed focal swollen glycogen containing mitochondria. For the developmental delay, a chromosomal microrarray was ordered. The chromosomal microarray revealed the patient to have 1q21 duplication syndrome and 16p11.2 deletion syndrome. Given the liver and muscle biopsy findings, a glycogen storage disease panel was sent which identified the patient to be hemizygous for a variant of uncertain significance denoted as p.Gly 131Val, c.392G > T in the PHKA2 gene. PKHA2 gene encodes the alpha subunit of hepatic phosphorylase kinase. This change in the PHKA2 gene was in a highly conserved region and had been reported in another patient with decreased enzymatic activity of the phosphorylase kinase and who had symptoms of GSD IX. Based on this, the patient was started on treatment for GSD IX, and his family met with a dietician.

Cirrhosis in a Young Child Due to Fatty Liver; Importance of Early Screening: A Case Report and Review of the Literature.

BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is the presence of chronic hepatic steatosis in the absence of infections, steatogenic medication use, metabolic/genetic disorders, malnutrition, or ethanol consumption. NAFLD encompasses a spectrum of liver damage varying from non-alcoholic fatty liver (NAFL) on the most clinically benign end of the spectrum to cirrhosis on the opposite extreme, where most liver-related morbidity and mortality occurs. CASE REPORT We report a case of a 9-year-old boy with history of obesity (BMI 32.1 kg/m² - 99th percentile) and non-alcoholic fatty liver disease, who was referred to our pediatric gastroenterology clinic with a 1-week history of vomiting and right upper-quadrant abdominal pain. A review of the past medical history revealed transaminitis for the last 4 years and a dietary regimen for the last 2 years with poor compliance and follow-up. An extensive workup revealed an SGPT of 327 unit/L, SGOT 186 unit/L, and triglycerides of 208 mg/dL; infectious, metabolic, genetic, and autoimmune etiologies were ruled-out. The median liver stiffness measured by Fibroscan was 14 kPa, consistent with F4 fibrosis, and the cap median value was 271 dB/mW, reflective of S2 steatosis. An ultrasound-guided core liver biopsy revealed steatohepatitis with bridging and encircling fibrosis consistent with early/evolving cirrhosis. CONCLUSIONS Although cirrhosis is rarely seen in pediatric patients with NAFLD, it should always be considered. Secondly, Fibroscan, a non-invasive imaging procedure, is a useful tool to assess the level of fibrosis and steatosis in patients with NAFLD; early evaluation of our patient could potentially have limited the progression to cirrhosis.

Pediatric Abdominal X-rays in the Acute Care Setting - Are We Overdiagnosing Constipation?

Introduction Constipation represents 3% of all office visits to pediatricians and 10% - 45% of consultations with pediatric gastroenterologists. It has been reliably established that the role of abdominal x-rays (AXR) in the diagnosis of constipation in pediatrics is limited; yet, significant overdiagnosis of constipation exists when plain abdominal x-rays are used in the acute setting for abdominal pain or to screen for other disorders. This results in loss of time, resources, exposure to unnecessary radiation, and potentially missing the primary diagnosis. The purpose of this study is to determine the sensitivity and specificity of AXR in diagnosing constipation in the acute setting. Objectives To determine 1) the sensitivity and specificity of plain AXR in the diagnosis of constipation and 2) the effect of age, race, gender, comorbid conditions, and practice setting on the diagnosis of constipation. Methods This study was a historical cohort study of children (two to 18 years of age) who were seen at Ascension St. John Children's Hospital between March 2015 - March 2018 and who had a plain AXR performed during an emergency department (ED) visit or inpatient stay. If AXR results contained keywords, such as "constipation," "stool load," "fecal retention," and "fecal load," the ambulatory medical record, Athena® (http://www.athenahealth.com), was searched to determine if the child had an ambulatory visit in the ensuing 45 days. Chart review was conducted to assess if the diagnosis of constipation was later confirmed by history and physical examination by a pediatrician or gastroenterologist at that visit. By comparing data from both encounters, the sensitivity and specificity of plain AXR in diagnosing constipation was assessed. All data were analyzed using the Statistical Package for Social Sciences (SPSS), v. 25.0 (IBM SPSS Statistics, Armonk, NY) and a p-value of 0.05 or less was considered to indicate statistical significance. Results Over the three-year study period, 1,383 AXRs were performed on 1,116 patients. The sensitivity of AXR in the diagnosis of constipation was 73.8%, specificity 26.8%, positive predictive value 46.4%, and negative predictive value of 54.3%. Pediatric gastroenterologists were more likely to diagnose constipation (63.2%) compared to pediatricians (41.4%) and pediatric surgeons (33.3%) (p = 0.04). Conclusions AXRs are not a reliable means of diagnosing constipation. Overall, we found similar sensitivity and specificity of AXR in diagnosing constipation compared to previous studies. Yet, our study gives new insight into the practices around diagnosing constipation in a single-center community hospital pediatric acute setting and the radiology department. This further emphasizes the need to review current practices and impart more education both in the acute care setting and radiology department.

Clinical and Histologic Liver Improvement in Siblings With Lysosomal Acid Lipase Deficiency After Enzyme Replacement.

OBJECTIVES: To assess the effect of long-term (104 weeks) treatment with recombinant sebelipase alpha (rhSA) on serum lipid and hepatic transaminase levels, and liver histopathology in 4 siblings diagnosed with lysosomal acid lipase deficiency (LAL-D). METHODS: Four male siblings from the same nonconsanguineous parents were diagnosed with the late-onset phenotype of LAL-D in 2015. Liver specimens were obtained by biopsy at baseline and after 104 weeks of enzyme replacement with rhSA (1 mg/kg, IV, every 2 weeks). Hepatic transaminase, lipid and lipoprotein levels were assessed at baseline and sequentially every 16 weeks for 104 weeks. Hepatic steatosis was evaluated from hematoxylin and eosin-stained specimens, and fibrosis was evaluated (Metavir-scoring system) from trichrome-stained specimens obtained at baseline and following 104 weeks of treatment with rhSA. RESULTS: All 4 siblings had improvement in their serum lipid and hepatic transaminase levels after treatment with rhSA. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels decreased from baseline by an average of 47% and 56%, respectively. The fasting triglyceride and low-density lipoprotein cholesterol (LDL-C) levels decreased from baseline by an average of 43% and 60%, respectively. Hepatic steatosis decreased from baseline grade 3 to posttreatment grade 1. Hepatic fibrosis did not advance following 104 weeks of treatment with rhSA and regressed in 1 sibling. CONCLUSIONS: Treatment with rhSA for 104 weeks in 4 siblings with LAL-D demonstrated improvement in their hepatic transaminase and serum lipid levels, accompanied by reduction of hepatic steatosis and no progression of fibrosis.

Report of a Fatal Case of Hemophagocytic Lymphohistiocytosis Syndrome and a Review of the Literature.

Hemophagocytic lymphohistiocytosis (HLH) is a rare condition in children, with a high mortality rate of 41.99%. Often, due to the atypical presentation of HLH, the syndrome is difficult to diagnose. We report a case of an atypical presentation of HLH and the diagnostic dilemma that we faced. An 11-year-old boy was hospitalized with recurrent fever, hepatosplenomegaly, and worsening jaundice. Initial laboratory workup revealed an elevated prothrombin time (PT), high bilirubin, increased alanine transaminase (ALT), and positive Epstein Barr virus (EBV) deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) and EBV immunoglobulin G (IgG). Based on our patient's presentation and initial laboratory findings, further extensive workup was done, which revealed cytopenias, hypofibrinogenemia, hemophagocytosis on biopsy, absent natural killer (NK) cell activity, high serum ferritin level, and high soluble CD25 (sIL-2 receptor); a diagnosis of HLH was made. He was started on broad-spectrum antibiotics, antivirals, antifungals, and cyclosporine. He became hypoxic and hypotensive and hence was intubated and started on vasopressors. However, his coagulation profile continued to deteriorate. He started bleeding from multiple sites and became unresponsive to ventilatory support, eventually dying as a result of complications of HLH. The ambiguous clinical presentation makes the diagnosis of this syndrome difficult. However, due to the high fatality rate, early recognition and prompt treatment are of utmost importance.

Clinical Variables as Predictors of First Relapse in Pediatric Crohn's Disease.

Introduction Crohn's disease (CD) is an immune-mediated inflammatory bowel disease (IBD) that can affect any portion of the gastrointestinal tract from the mouth to the anus. The clinical course of CD is characterized by periods of symptomatic relapse and remission. Clinical variables may identify a subset of patients with CD at risk for relapse. Identifying these patients, and early stratification-based treatment would be of utmost clinical importance in optimizing the management and is likely to improve long-term disease outcome. In pediatric-onset IBD there is a paucity of data for predicting clinical behavior and results are conflicting. With this background, we hypothesized that routinely measured clinical variables at the time of diagnosis would predict relapse in patients with CD, and sought to investigate the clinical predictors of relapse present at the time of diagnosis in our patient population. We further compared differences in clinical variables and laboratory values for patients who relapsed early, compared with those who relapsed late. Methods We conducted a retrospective chart review of patients diagnosed with CD by clinical, radiological, endoscopic and histological criteria at St. John Providence Children's Hospital pediatric GI clinic between 01/2006 and 12/2014. Patients were followed until they had their first relapse or for three years from diagnosis, whichever was earlier. Variables studied included demographic factors (age, gender, race, BMI, BMI percentiles and family history of IBD), presenting symptoms (blood in stools, nocturnal stools, fever, and extra-intestinal manifestations), phenotypic characteristics (using Montreal classification), and laboratory data [white blood cell (WBC) count, hemoglobin, hematocrit, platelet count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP)]. Results Twenty-nine patients were included in the study. One was lost to follow up, and 28 were included in the analyses. The relapse rate was 50% at three years, and 32% patients relapsed within one year of diagnosis. Low BMI percentile at diagnosis (41.5 ± 28.8 vs. 18.0 ± 20.3; p-value 0.03) was a predictor of relapse. Comparing early relapse to those who relapsed late, there were no statistically significant differences between the two groups. Conclusions Low BMI percentile at presentation was associated with increased risk of relapse, suggesting that routinely measured clinical variables may have role in predicting first relapse in this patient population. There was no significant difference in the variable comparing patients who relapsed early vs. those who relapsed late. Future prospective studies with larger sample sizes need to be done to predict relapse.

MPV17-related mitochondrial DNA maintenance defect: New cases and review of clinical, biochemical, and molecular aspects.

Mitochondrial DNA (mtDNA) maintenance defects are a group of diseases caused by deficiency of proteins involved in mtDNA synthesis, mitochondrial nucleotide supply, or mitochondrial dynamics. One of the mtDNA maintenance proteins is MPV17, which is a mitochondrial inner membrane protein involved in importing deoxynucleotides into the mitochondria. In 2006, pathogenic variants in MPV17 were first reported to cause infantile-onset hepatocerebral mtDNA depletion syndrome and Navajo neurohepatopathy. To date, 75 individuals with MPV17-related mtDNA maintenance defect have been reported with 39 different MPV17 pathogenic variants. In this report, we present an additional 25 affected individuals with nine novel MPV17 pathogenic variants. We summarize the clinical features of all 100 affected individuals and review the total 48 MPV17 pathogenic variants. The vast majority of affected individuals presented with an early-onset encephalohepatopathic disease characterized by hepatic and neurological manifestations, failure to thrive, lactic acidemia, and mtDNA depletion detected mainly in liver tissue. Rarely, MPV17 deficiency can cause a late-onset neuromyopathic disease characterized by myopathy and peripheral neuropathy with no or minimal liver involvement. Approximately half of the MPV17 pathogenic variants are missense. A genotype with biallelic missense variants, in particular homozygous p.R50Q, p.P98L, and p.R41Q, can carry a relatively better prognosis.

Predictors of positive esophagogastroduodenoscopy outcomes in children and adolescents: a single center experience.

BACKGROUND: Esophagogastroduodenoscopy (EGD) has become a key element in the diagnosis and therapy of many gastrointestinal diseases affecting children. The aim of this study was to evaluate predictors of positive outcomes in children undergoing their first diagnostic EGD with biopsies at a single center. RESULTS: This retrospective study was based on findings from existing EGD and histopathological reports. All procedures were performed between July 2006 and July 2013. Details of each patient's clinical presentation and EGD were abstracted from medical records to determine the predictors of positive EGD outcomes. A total of 1133 records of patients between the ages of 0 and 18 years old were evaluated. Of these patients, 51.5% (n = 573) were female and 24.5% (n = 278) were younger than 4 years old. The mean age at the time of EGD was 9.6 ± 5.7 years (mean ± standard deviation). The most common indications for the procedure were abdominal pain (54.9%) and emesis (31.9%). The overall prevalence of any endoscopic abnormality was 54.5% and the overall prevalence of any histological abnormality was 59.1%. A multivariate logistic regression found that patients 12 years or older (odds ratio, OR = 1.46; 95% confidence interval, CI 1.31-1.63), African-American race (OR = 2.20; 95% CI 1.45-3.34), dysphagia (OR = 1.96; 95% CI 1.28-3.00) and positive celiac antibodies (OR = 2.25; 95% CI 1.52-3.34) were all significant independent predictors of a positive EGD outcome. CONCLUSIONS: Several clinical variables were found to be independent predictors of positive EGD outcomes in children and adolescents. Prospective studies using standardized definitions of clinical variables and endoscopy outcomes are needed to further understand predictors of positive EGDs.

Lysosomal acid lipase deficiency in all siblings of the same parents.

We present 4 normal-weight sibling children with lysosomal acid lipase deficiency (LAL-D). LAL-D was considered in the differential diagnosis based on the absence of secondary causes and primary inherited traits for their marked hyperlipidemia, together with unexplained hepatic transaminase elevation. Residual lysosomal acid lipase activity confirmed the diagnosis. DNA sequencing of LIPA indicated that the siblings were compound heterozygotes (c.894G>A and c.428+1G>A). This case describes the unusual occurrence of all offspring from the same nonconsanguineous mother and father inheriting compound heterozygosity of a recessive trait and the identification of an apparently unique LIPA mutation (c.428+1G>A). It highlights the collaborative effort between a lipidologist and gastroenterologist in developing a differential diagnosis leading to the confirmatory diagnosis of this rare, life-threatening disease. With the availability of an effective enzyme replacement therapy (sebelipase alfa), LAL-D should be entertained in the differential diagnosis of children, adolescents, and young adults with idiopathic hyperlipidemia and unexplained hepatic transaminase elevation.

Seasonal variations in onset and exacerbation of inflammatory bowel diseases in children.

BACKGROUND: Studies have suggested that inflammatory bowel diseases (IBD) follow a seasonal pattern with regard to their onset and exacerbations. The aim of this study is to determine if there is any seasonal pattern to the onset and exacerbation of IBD in the pediatric population and if the birth of children diagnosed with IBD follows a seasonal pattern. METHODS: Patients between the ages of 1 and 21 years and with a diagnosis of IBD established between July 1992 and July 2012 were included. Their onset and exacerbations of IBD (year and season) were recorded. The birth dates of the patients were aggregated to determine whether a seasonal birth pattern existed amongst them. RESULTS: A total of 170 children were included in this study; 34% of patients had their onset in the fall and 19% of them had their onset in the summer. The total number of documented exacerbations was 358 and the median number of exacerbations was two, with a range of 1-11. IBD exacerbations were generally uniformly distributed throughout the year. We did not observe any specific season where children with IBD tended to be born. CONCLUSIONS: Our data suggests that the onset of symptoms of IBD tends to have a seasonal trend with the highest incidence in the fall. However, we did not observe any association between seasonality and exacerbations in the pediatric population. Moreover, there was no specific season in which children with IBD tended to be born in greater numbers.

Eosinophilic esophagitis associated with celiac disease in children.

BACKGROUND: Celiac disease (CD) and eosinophilic esophagitis (EoE) are distinct diseases of the gastrointestinal tract with specific clinico-pathological characteristics. Recent studies have found higher rates of EoE in patients with CD than in the general population. Our aim was to estimate the incidence of EoE among children who were diagnosed with CD over a 42-month period. METHODS: The study included patients diagnosed with CD based on endoscopy and histopathological findings between January 2010 and June 2013. Histopathology reports of esophageal biopsies were reviewed to identify all cases of EoE. The patients' presenting symptoms, laboratory evaluations, endoscopic and histopathological findings, treatments, and follow-ups were analysed. RESULTS: Fifty-six patients with CD were identified, of whom six (10.7%) were diagnosed with both CD and EoE. Four of these patients presented with abdominal pain and diarrhea, two presented with failure to thrive, and three presented with food allergies. Endoscopic and histopathological changes typical of EoE were observed in all six patients. During follow-up, two patients showed significant improvement with the gluten-free diet and a proton-pump inhibitor (PPI). Two patients improved with the elimination diet and two patients were treated with topical corticosteroid therapy. Endoscopic appearance was normal in all children on follow-up endoscopy after treatment. Biopsy samples also showed resolution of the histologic features of EoE in all of the children. CONCLUSION: The incidence of EoE in our cohort of children with CD was 10.7%, which is higher than what has been reported for the general population. In all children undergoing upper gastrointestinal endoscopy for suspected CD, coexistence of EoE should be considered.

1-day bowel preparation with polyethylene glycol 3350 is as effective and safe as a 3-day preparation for colonoscopy in children.

BACKGROUND: Polyethylene Glycol 3350 (Miralax®) without electrolytes is commonly used for 3-4 days as bowel preparation for colonoscopy in children. One-day preparation has been anecdotally reported to be effective but there are few published prospective studies comparing the safety and efficacy of one-day preparation with that of three-day preparation. This study was conducted to compare the efficacy and safety of a one-day bowel preparation with Miralax® with that of a three-day preparation for colonoscopy in children. METHODS: We conducted a prospective, randomized controlled trial with children age 2-21 yrs. undergoing elective colonoscopy. Patients were randomly assigned to receive Miralax® for either one or three days. Children with known electrolyte disturbances, dehydration, fecal impaction, metabolic or renal disease were excluded. A metabolic panel was monitored before and after bowel preparation. Subjects reported the tolerability and side effects of Miralax® via a survey. Effectiveness of the bowel preparation was assessed using a stool diary and a bowel cleansing scale during colonoscopy. RESULTS: 32 subjects were enrolled; 18 received one-day bowel preparation and 14 received 3-day preparation. There were no differences between the groups in efficacy of bowel preparation based on colonoscopic grading or the safety of the preparation. One-day preparation was as well tolerated as three-day preparation. CONCLUSION: Miralax® used one day as bowel preparation for elective colonoscopy in children is safe, effective and well tolerated. Physicians should consider offering a one-day option for bowel preparation, which would allow children to miss fewer days of school prior to colonoscopy. TRIAL REGISTRATION NUMBER: NCT02174497. Date of Registration: 02 May, 2014 URL of register: clinicaltrials.gov.

Eosinophilic esophagitis in children and adolescents: epidemiology, clinical presentation and seasonal variation.

BACKGROUND: Eosinophilic esophagitis (EoE) is defined by infiltration of eosinophils in the esophageal mucosa (>20 eosinophils/hpf). The epidemiology and seasonal variation have not been well studied in children and adolescents. METHODS: Review of all esophageal biopsies performed from January 2001 to December 2006 on patients younger than 21 year of age, focusing on demographics, onset and duration of presenting symptoms, history of allergies and endoscopic findings. RESULTS: A total of 753 upper endoscopies were performed, 44 of which showed histologic evidence of EoE (5.8 %). Fifty percent of all EoE endoscopies were grossly normal. Onset of symptoms was 23 % in the spring, 29 % in the summer, 23 % in the fall and 25 % in the winter. More cases (36 %) were diagnosed in the fall. Time between onset of symptoms and diagnosis was 115 ± 145 days (mean ± SD). The most common presenting symptoms were vomiting (61 %), dysphagia (39 %), abdominal pain (34 %), feeding disorders (14 %), heartburn (14 %), food impaction (7 %), vague chest pain (5 %) and diarrhea (5 %). Children presenting with vomiting and feeding disorders were younger (p < 0.02), whereas children presenting with heartburn and dysphagia were older (p < 0.02). CONCLUSIONS: The incidence of EoE did not increase between 2001 and 2006. Onset of symptoms did not vary by season, indicating that allergens triggering EoE are present all year around. Vomiting and feeding disorders are seen in young children, while dysphagia and heartburn are seen in older children. As endoscopic findings were normal in 50 % of cases, an esophageal biopsy should be performed in all patients with suspected EoE.

Outcomes after laparoscopic cholecystectomy in children with biliary dyskinesia.

Our objectives were to determine the prevalence of biliary dyskinesia (BD) as an indication for cholecystectomy in children and to identify presenting clinical findings and optimal ejection fraction (EF) associated with the resolution of symptoms after surgery. We conducted a retrospective review of medical records of 212 pediatric patients who underwent cholecystectomy from August, 1998 to November, 2006. Patients who met criteria for BD had their short-term outcomes examined by record review and their long-term postoperative outcomes recorded by questionnaire. To compare EF and clinical presentation to symptom resolution or outcome, χ tests were used. Logistic regression was used to evaluate possible predictors of symptom resolution. BD was the indication for cholecystectomy in 20% of patients (44 of 212). Short-term outcome was not predicted by any of the collected variables. An EF ≤11% predicted higher rate of symptom resolution (P=0.02). Although patients with specific right upper quadrant pain had higher rates of long-term improvement than those with nonspecific abdominal pain (57.9% vs. 18.2%), this did not reach significance (P=0.057). The only predictor emerging from the logistic regression was EF cutoff at 11% (odds ratio=17.5; 95% confidence interval, 1.756-174.418). In this series, symptoms of BD were more likely to be resolved by cholecystectomy in children with EF ≤11%.

Human herpesvirus 6 infection mimicking juvenile myelomonocytic leukemia in an infant.

In vitro cell culture studies of bone marrow and peripheral blood progenitor cells from patients with juvenile myclomonocytic leukemia (JMML) consistently show spontaneous proliferation and selective hypersensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF). This GM-CSF hypersensitivity dose-response assay has become a component of the international diagnostic criteria for JMML. The authors report a 2-week-old boy with perinatal human herpesvirus 6 (HHV-6) infection in whom in vitro bone marrow culture studies suggested the diagnosis of JMML by showing increased spontaneous proliferation, inhibition of this growth by anti-GM-CSF antibodies, and hypersensitivity to GM-CSF. Polymerase chain reaction viral studies from whole blood DNA and the shell vial viral culture assay were both positive for HHV-6. The patient's condition improved with expectant treatment, with an eventual return to normal blood counts and resolution of hepatosplenomegaly. This case of perinatal HHV-6 infection shows that viruses can initially mimic the in vitro culture results found in patients with JMML. It also illustrates that patients suspected of having JMML should be observed if there are no signs of progressive disease and concurrent features suggestive of viral infection.