SLC5A1 Mutations in Saudi Arabian Patients With Congenital Glucose-Galactose Malabsorption.

Congenital glucose-galactose malabsorption (cGGM) is a rare autosomal recessive disorder, caused by mutations in the SLC5A1 gene, encoding the sodium/glucose cotransporter 1, which may result in severe life-threatening osmotic diarrhea due to the accumulation of unabsorbed sugars in the intestinal lumen. If treated early with elimination of glucose and galactose from the diet, patients usually recover and develop normally. We present clinical and molecular data from 16 unrelated cGGM diagnosed Saudi patients from consanguineous families with majority of them having previous positive family history of cGGM. Sanger sequencing for the full coding regions of SLC5A1 for all patients resulted in the identification of 4 allelic variants in a homozygous state. Two mutations are novel; c.265G>A (p.G89R) and c.1304 G>A (p.G435D), and 2 have been previously reported to cause cGGM, c.765 C>G (p.C255W) and c.1136 G>A (p.R379Q). This is the first report delineating the clinical and molecular basis of cGGM in patients from this region.

Novel PHKG2 mutation causing GSD IX with prominent liver disease: report of three cases and review of literature.

Glycogen storage disease type IX (GSD IX) is a common form of glycogenosis due to mutations in PHKA1, PHKA2, or PHKB and PHKG2 genes resulting in the deficiency of phosphorylase kinase. The first two genes are X-linked while the latter two follow an autosomal recessive inheritance. The majority of cases of GSD IX are attributed to defects in PHKA2 which usually cause a mild disease. We report three patients with PHKG2-related GSD IX presenting with significant hepatic involvement, fibrosis, and cirrhosis. Interestingly, the homozygosity mapping resolved a dilemma about an erroneously normal phosphorylase kinase activity in patient 1. The novel mutation found in all the three patients (p.G220E) affects the catalytic subunit of the phosphorylase kinase. Increasing evidence shows that patients with PHKG2 mutations have a severe hepatic phenotype within the heterogeneous GSD IX disorder. Therefore, defect in PHKG2 should be considered in patients with suspected glycogenosis associated with significant liver fibrosis and cirrhosis.

Surgical consequences in infants with delayed diagnosis of congenital chloride diarrhea.

Despite the usual typical presentation, congenital chloride diarrhea (CCD) poses multiple diagnostic challenges. It has an incidence of 1/5000 in Saudi Arabia. CCD can mimic intestinal obstruction and result in avoidable surgical interventions. Contributing factors are abdominal distension and the watery (urine-like) diarrhea that is often interpreted as delayed passage of meconium. Surgical interventions would unnecessarily increase the morbidity. Therefore, a high index of suspicion and educating neonatologists, general pediatricians, and pediatric surgeons regarding this diagnostic entity is essential. Here we describe five such cases.

Characteristics of pediatric ulcerative colitis in Saudi Arabia: a multicenter national study.

BACKGROUND: Despite the extensive reporting of pediatric ulcerative colitis (UC) from industrialized developed countries, reports from developing countries are limited to small-case series from single centers. The objective of our large multicenter study was to determine the clinical, laboratory, endoscopic characteristics of UC in children from a developing country, Saudi Arabia. DESIGN AND SETTINGS: A retrospective study of children diagnosed with UC under the age of 18 years during the period from 2003 to 2012. METHODS: Patients enrolled from 15 medical centers from different regions in Saudi Arabia. A unified database collection form specifically designed for this study was completed by all participating centers. RESULTS: A total of 188 children were diagnosed with UC during the study period (97 males [51.6%] and 91 females [48.4%]). The mean age at diagnosis was 9.1 years, and the mean duration of symptoms before diagnosis was 8.7 months. Consanguinity was present in 57 cases (32.6%), and the family history of inflammatory bowel disease (IBD) was noted in 16 cases (9%). The most common clinical presentation was blood in stool (90%), followed by diarrhea (86%) and abdominal pain (62%). Laboratory investigations revealed elevated erythrocyte sedimentation rate (82%), anemia (75%), thrombocytosis (72%), and hypoalbuminemia (33%). The extent of the disease was pan colonic in 46.1%, and confined to left side of colon and rectum in 23% and 9.6% of the cases, respectively. CONCLUSION: This demographically pediatric IBD retrospective study revealed age-related variation in the distribution of IBD. Clinical presentation, with a high prevalence of positive consanguinity and positive family history, was noted in young patients with UC. The data from this study indicate that UC is increasingly recognized in Saudi Arabia and show many similarities to data from North America and Europe.

Gastrointestinal basidiobolomycosis: mimicking Crohns disease case report and review of the literature.

Gastrointestinal basidiobolomycosis (GIB) is an unusual fungal infection that manifests in the skin and rarely involves other systems. All of the few cases of GIB reported so far were diagnosed with difficulty, necessitating laparotomy and resection of the inflamed part of the bowel. We report a child with GIB who was successfully diagnosed endoscopically without surgical intervention.

Chronic diarrhea and skin hyperpigmentation: a new association.

BACKGROUND/AIMS: The objective of this study was to describe patients with chronic diarrhea and abnormal skin hyperpigmentation with distinct distribution. METHODS: This is a retrospective review of children who presented with diarrhea and skin hyperpigmentation. The clinical presentation, laboratory investigations as well as endoscopic and histological data were reviewed. RESULTS: Seven patients with chronic diarrhea had abnormal skin hyperpigmentation with distinct distribution and presented in the first two months of life. Six patients had other features such as abnormal hair and facial dysmorphism. Mental retardation was reported in one patient. Consanguinity was positive in six patients, and there was family history of consanguinity in four patients, with two patients being siblings. No significant immunodeficiency was reported. Intestinal biopsies were obtained in six patients and showed active chronic inflammation in three patients, partial villous atrophy in two patients, and eosinophilic infiltrate with mild villous atrophy in one patient. Colonic biopsies showed mild focal colitis in three patients and mild colitis with eosinophilic infiltrate in one patient. Skin biopsies showed a greater number of melanophagies with fibrosis of papillary derma in two patients but skin biopsy was normal in one patient. The hair of two patients was analyzed by electron microscopy, which showed an abnormal pattern with decreased pigmentation and diameter; however, its chemical analysis was normal. Two other patients had trichorrhexis nodosa, but no abnormalities were seen in one patient. Chromosomal number was normal in three patients. One patient died because of sepsis, and only one patient was dependent on total parenteral nutrition. CONCLUSIONS: We believe that this association might represent a new syndrome with an autosomal recessive inheritance that warrants further studies.