Clinical, Laboratory, Radiological, and Genetic Characteristics of Pediatric Patients with Alagille Syndrome.

Background: Alagille syndrome (ALGS) is an autosomal dominant disease caused by JAG1 or NOTCH2 mutation. It is diagnosed by the presence of three out of five features: characteristic facies, posterior embryotoxon, peripheral pulmonary stenosis, vertebral defects, and interlobular bile duct paucity. This study aimed to review the prevalence, clinical presentations, diagnosis, treatment, and outcome of patients with ALGS. Materials and Methods: This is a retrospective review of patients with ALGS at the Pediatric Department, Salmaniya Medical Complex, Bahrain, between August 1994 and October 2022. The diagnosis was based on clinical, laboratory, radiological, histopathological, and genetic findings. Results: Five patients were found to have ALGS. The prevalence of ALGS in Bahrain was 1.04 patients per 100,000 (0.001%). Four were Bahraini and three were females. Median birth weight was 2.3 (2.3-2.5) kg. All patients presented at the time of birth with low birth weight, cholestatic jaundice, clay-colored stool, heart murmur, and dysmorphic facial features. All had congenital heart diseases, two had butterfly vertebrae, and one had posterior embryotoxon. All had elevated liver enzymes and normal abdominal ultrasound. Three had positive hepatobiliary iminodiacetic acid scan and one had bile duct paucity in liver biopsy. Three had intraoperative cholangiogram. Four were positive for JAG1 mutation. All received ursodeoxycholic acid and fat-soluble vitamins. Two required liver transplantation. Conclusion: ALGS is a rare disorder in Bahrain. Diagnosis is challenging as the disease can be associated with or misdiagnosed as biliary atresia. Patients with ALGS are at high risk of morbidity either by unnecessary intraoperative cholangiogram or unavoidable liver transplantation.

The Prevalence of Iron and Vitamin D Deficiencies in Pediatric Patients With Inflammatory Bowel Disease in Bahrain.

Introduction Inflammatory bowel diseases (IBD) are chronic diseases that can affect nutrient absorption leading to micronutrient deficiencies and biochemical abnormalities.This study aimed to assess certain serum micronutrients and nutritionally related biochemical markers levels in patients with pediatric IBD and to compare the actual levels and the prevalence of micronutrients deficiencies and biochemical abnormalities between patients with Crohn's disease (CD) and those with ulcerative colitis (UC). Methods A retrospective cross-sectional study reviewing medical records of patients with IBD was conducted in the pediatric department, Salmaniya medical complex, Bahrain, from 1 January 1984 to 31 December 2021. Demographic data and laboratory results related to micronutrients and biochemical markers including full blood count, total protein, albumin, globulin, iron, ferritin, folic acid, vitamin B12, calcium, phosphorous, magnesium, and vitamin D levels were collected upon presentation before starting the treatment. Nutritional deficiencies were compared based on sex, nationality, type of IBD, age at presentation, disease duration, weight at diagnosis, and inflammatory markers levels including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Results Of 157 patients with pediatric IBD, 117 (74.5%) were included. Sixty-six (56.4%) patients were males. Sixty-six (56.4%) had CD and 51 (43.6%) had UC. No patient had indeterminant colitis. The mean age at presentation was 10.8±3.8 years. Most patients had one or more micronutrient deficiencies (n=110, 94%). Anemia was a common finding (n=79/116, 68.1%), with iron deficiency anemia (IDA) being predominant. Low iron levels were noted in 64/77 (83.1%) patients with a median of 5.0 (2.0-9.3) µmol/L (normal range, 11.6-31.3); isolated iron deficiency (ID) in 11/18 (61.1%) and IDA in 53/59 (89.8%) patients. Vitamin D deficiency was the second most common (n=45/61, 73.8%). Serum albumin, ferritin, calcium, phosphorous, and magnesium were deficient in 29.2%, 27.8%, 31.7%, 12.5%, and 10%, respectively. One patient had vitamin B12 deficiency while none had folate deficiency. Patients with CD had significantly lower serum iron (5.4±5.6 versus 8.1±6.09 µmol//L, p=0.02) and lower serum protein (71.7±8.7 versus 75.4±9.9 g/L, p=0.043) but higher serum ferritin (45 (19-110.2) versus 21.3 (10.3-51.2) µg/L, p=0.046) compared to those with UC. Elevated ESR was noted in 62/105 (59.1%) patients while high CRP was found in 67/104 (64.4%). Patients with low iron had higher ESR (28 (17-47) versus 14 (10-33) mm/h, p=0.028) and higher CRP (13.3 (1.6-42) versus 1.8 (0.9-4.6) mg/L, p=0.019) levels compared to those with normal levels. Conclusion Patients with pediatric IBD are at risk of multiple micronutrient deficiencies and biochemical abnormalities. Iron and vitamin D deficiencies are the most frequent. Patients with CD are more prone to have lower serum iron and protein levels than those with UC. ID was associated with elevated inflammatory markers.

Linear Growth Impairment in Patients With Pediatric Inflammatory Bowel Disease.

Introduction Linear growth impairment (LGI) is one of the complications of pediatric inflammatory bowel disease (IBD). This study aimed to assess the linear growth of patients with pediatric IBD and to detect the frequency and the possible risk factors of LGI. Methods A retrospective cross-sectional review of medical records of patients with pediatric IBD was conducted in the pediatrics department, Salmaniya Medical Complex, Bahrain, from 1984 to 2019. Demographic and anthropometric data were gathered. World Health Organization (WHO) standards and references were used to define LGI. According to WHO, stunting and severe stunting were defined as length/height for age of <-2 standard deviations and <-3 standard deviations from age and sex-specific reference means, respectively. To determine the possible risk factors for LGI, stunted patients were compared with normal height patients in regard to demographic data, clinical presentations, and treatment used. Results Out of 130 patients with pediatric IBD, 88 (67.7%) had anthropometric data available. Fifty-five (62.5%) were males. Forty-seven (53.4%) had Crohn's disease and 41 (46.6%) had ulcerative colitis. The mean age at presentation was 10.7±3.8 years. The median age at the time of growth measurement was 14.2 (interquartile range=12.1-24.4) years. Fifteen (17%) patients were stunted, and seven (46.7%) of those stunted patients were severely stunted. Weight at presentation was lower in stunted patients (21.6±5.9 kilograms) compared to normal height patients (31±13.4 kilogram) (p=0.048). Sex, delivery type, birth weight, height at presentation, age at presentation, age at growth measurements, IBD type, disease duration, presence of extraintestinal manifestations, and prednisolone and biologic therapy use were not significant factors of stunting. Conclusion Patients with pediatric IBD have a high prevalence of LGI compared to the general population. Low weight at disease presentation is the only significant risk factor for LGI. This might indicate that IBD as a disease by itself is having the main negative impact on linear growth.

Celiac disease in children: Increasing prevalence and changing clinical presentations.

BACKGROUND: Celiac disease (CD) is a chronic autoimmune enteropathy. It results from genetic predisposition and exposure to gluten-containing food. The prevalence and presentation of CD vary among populations. PURPOSE: This study aimed to describe the prevalence and clinical characteristics of CD in children in Bahrain. METHODS: We retrospectively reviewed the medical records of children diagnosed with CD in the pediatric department, Salmaniya Medical Complex, Bahrain, in 1988-2018. Their clinical, biochemical, serological, and histopathological findings were documented. Adherence to the recommended gluten-free diet (GFD) was assessed. RESULTS: Of 86 patients with CD, 67 were included. The CD prevalence was 0.02%. A significant increase in prevalence in the last decade was observed (P<0.0001). Thirty-eight patients (56.7%) were males. The median (interquartile range) age at presentation was 4.45 (1.5-7.3) years. A family history of CD was positive in 13 out of 43 patients (30.2%). Pallor and failure to thrive were the most common presentations. The most frequent associated disease was iron-deficiency anemia in 23 patients (69.7%). Positive serology was found in 32 of 45 patients (71.1%). Marsh-Oberhuber type III was found in 16 of 35 patients (45.7%). Seropositive patients were significantly older (P=0.025) and had more severe duodenal histology (P=0.002). Adherence to GFD was poor in 27 patients (64.3%). CONCLUSION: This study revealed a significant increase in CD prevalence over the last decade. Atypical presentations were frequent. Most patients had poor adherence to GFD.