ORAI1 defect in a patient with disseminated CMV infection and severe hypotonia.

BACKGROUND: A clinical presentation similar to severe combined immunodeficiency (SCID) with defective T cell activation but normal lymphocyte development occurs due to certain molecule defects including ORAI1- and STIM1. CASE: A four-month-old girl sufferd from fever, restlessness, diarrhea, and poor weight gain following the neonatal period. There was consanguinity and a positive family history. She had hypotonia and spontaneous opisthotonic posture. Refractory and extensive CMV infections were detected; immunological investigations revealed normal quantitative immunoglobulins and low numbers of CD3+, CD4+, and CD8+ cells. The next generation sequencing analysis revealed a mutation in the ORAI1 gene. CONCLUSIONS: The present patient`s history of refractory and widespread CMV infections shows a clinically substantial reduction in resistance against opportunistic microorganisms. This case emphasizes the importance of considering STIM1 and ORAI1 defects in patients with SCID phenotype and neurologic involvement, such as hypotonia.

Significance of intestinal alkaline phosphatase in predicting histological activity of pediatric inflammatory bowel disease.

BACKGROUND: Intestinal alkaline phosphatase (iAP) is an intestinal brush border enzyme that is one of the factors involved in the pathogenesis of inflammatory bowel disease (IBD). The aim of the study was to investigate the relationship between iAP enzyme and histological inflammatory activity in patients with IBD. METHODS: A total of 44 children were enrolled in this study including IBD patients (n=24; 12 Crohn`s disease [CD] and 12 ulcerative colitis [UC]) and controls (n=20). Anti-human iAP antibody stained ileocolonoscopic biopsy specimens were graded for the terminal ileum and each section of the colon. Hematoxylin-eosin stained sections were used to determine inflammatory activity. Histopathological findings were compared in pre- and post-treatment biopsies of each group and with the control group (CG). RESULTS: A low grade of iAP staining was detected in IBD patients compared to the CG (p=0.02). iAP was remarkably concentrated in the terminal ileum (TI) and especially in region 1, which involved the apical surface, brush border, and epithelial cells. A significant negative correlation was found between the grade of iAP staining and inflammatory activity both in pre- and post-treatment biopsies (p=0.02, p=0.008, respectively) in the terminal ileum of CD patients. Likewise, pre-treatment biopsies of UC and CD patients and biopsies of the CG were compared with each other according to the grade of iAP staining. There were significant negative correlations for CD patients compared to UC and the CG in region1 of TI, and regions 1 and 2 (lamina propria and goblet cells) of the colon (p= 0.015, p= 0.006, p < 0.001, respectively). CONCLUSIONS: As a histological marker, iAP can be of value in monitoring the histological activity of IBD, particularly in remarkable inflammation in the small intestine.

A very rare cause of protein losing enteropathy: Gaucher disease.

BACKGROUND: Mesenteric lymphadenopathy is a rare manifestation of Gaucher disease (GD) in children and can be accompanied by protein losing enteropathy (PLE). PLE is a difficult-to-treat complication of GD. To date, only a few pediatric GD cases with PLE and massive mesenteric lymphadenopathies have been reported. CASE: Here, we report a girl with chronic neuronopathic GD, whose disease course was complicated by massive mesenteric lymphadenopathies with resultant protein losing enteropathy despite a regular and appropriate enzyme replacement therapy of 60 IU/kg/biweekly until the development of mesenteric lymphadenopathies and 120 IU/kg/biweekly thereafter. CONCLUSIONS: PLE is a devastating and life threatening complication of GD developing despite long term use of high dose ERT. Clinicians should be alert for this complication particularly in GD patients presenting with progressive abdominal distension, edema, ascites and diarrhea or in patients who have already developed mesenteric lymphadenopathies. Timely diagnosis may allow early intervention with previously suggested surgical or medical treatment options. Although there is no specific and effective treatment, surgical and aggressive medical interventions in addition to ERT were reported to relieve diarrhea and halt progression of mesenteric lymphadenopathies.

Ascites: a loadstar for the diagnosis and management of an intracranial tumor.

BACKGROUND: Ascites is defined as abnormal fluid retention in the peritoneal cavity and it can be encountered at any age including fetal life. Ascites mostly results from cirrhosis, chronic renal disease and heart failure in childhood. However, there are various reasons for cirrhotic and non-cirrhotic ascites in the pediatric age. Cerebrospinal fluid ascites is one of the rarest. CASE: A 3.5- year- old Sudanese boy who underwent right-sided ventriculoperitoneal shunt surgery for hydrocephalus 10 months ago was admitted to the Neurosurgery Intensive Care Unit for intracranial tumor surgery. He had neurologic deterioration and ascites accumulation for the last 4 months. He was consulted with the pediatric gastroenterologist to exclude the reasons causing ascites after admission. No chronic liver, renal or heart disease was shown. The gross appearance of ascitic fluid was so clear that it resembled the cerebrospinal fluid and laboratory analysis results were compatible with transudate. The magnetic resonance imaging identified a mass in the left lateral ventricle. From the pediatrician`s perspective, overproduction of cerebrospinal fluid from a tumor was assumed and shunt exclusion was proposed to alleviate ascites. After the externalization of the stunt and external ventricular device implementation, no further ascites occurred. The patient had a successful tumor excision and discharged after gaining oral feeding ability and sufficient weight gain. CONCLUSION: In case of intractable ascites occurrence after a ventriculoperitoneal shunt placement, a pediatrician should consider etiologies resulting in imbalance of absorption and secretion function of cerebrospinal fluid.

Risk factors associated with clinically significant gastrointestinal bleeding in pediatric ED.

INTRODUCTION: Gastrointestinal bleeding is a common problem in pediatric emergency department (PED). Some of these patients can lose significant amount of blood which may lead to shock. The aim of this study is to determine the risk factors predicting clinically significant gastrointestinal (GIS) bleeding in patients presenting to PED. METHODS: This study was performed prospectively from January 1st 2013 to December 31th 2013 in patients with upper or lower GIS bleeding. Clinically significant GIS bleeding was defined as >2g/dL hemoglobin decrease at any time during observation in PED, need for erythrocyte transfusion or need for rapid endoscopic evaluation. RESULTS: 105 patients were enrolled, 81 of which were eligible for the study. Twenty two patients (26,8%) had clinically significant GIS bleeding. These patients have significantly more commonly have upper GI bleeding and symptoms of melena, pallor and tachycardia. Initial laboratory findings revealed lower hemoglobin, RBC and albumin levels with higher WBC and BUN levels. They need significantly more nasogastric tube placement and PPI and H2 blocker treatment. Final diagnosis included more gastritis and peptic ulcers. These patients have less hematochezia, less lower gastrointestinal bleeding and less commonly diagnosed as acute gastroenteritis or Mallory Weiss tear as a final diagnosis. CONCLUSIONS: Pediatric emergency physicians should be aware of clinical and laboratory parameters of patients with clinically significant GIS bleeding to predict which patients are under risk of life threatening blood loss. Patients who have melena, pallor, tachycardia, anemia and uremia at presentation are more prone to have significant GIS bleeding.

Deoxyguanosine kinase deficiency: a report of four patients.

BACKGROUND: Hepatic involvement is a common feature in childhood mitochondrial disorders. Deoxyguanosine kinase (DGUOK) deficiency is one of the mitochondrial DNA depletion syndromes associated with hepatocerebral syndrome. Hepatic disease and neurologic dysfunction occurs within weeks after birth. Low birth weight is one of the common features. This study aims to describe the clinical and laboratory features of four infants carrying four different pathogenic variants in the DGUOK gene. CASE PRESENTATION: Common clinical findings were progressive cholestatic liver failure, hypoglycemia, hypotonia and rotatory nystagmus in our DGUOK deficiency patients. Lactic acidosis, elevated serum tyrosine and ferritin levels were the striking laboratory features. Cholestasis, iron deposits, microvesicular steatosis and fibrosis were the histopathological findings seen in liver biopsies of two patients. All patients died with multi-organ failure between the ages of 42 days and 6 months. CONCLUSIONS: While neurologic findings may occur later in the course of the disease, elevated serum tyrosine levels may alert the physicians to a DGUOK deficiency in a baby with hepatopathy in the presence of the mentioned signs. Early diagnosis is important not only for genetic counseling but also for a possible liver transplantation.