Celiac Disease (CD) is a lifelong autoimmune intestinal disorder resulting from an abnormal response of the small bowel mucosa to gluten peptides derived from food. Gluten protein is found in all forms of wheat and related grains like rye, barley, and triticale. In individuals genetically susceptible to CD, the ingested gluten triggers an autoimmune response that damages the intestinal villi, leading to malabsorption and malnutrition. Symptoms of the disease are related to defects in absorption of nutrients, and include diarrhea, failure to thrive, fatigue, weight loss, anemia (due to iron malabsorption), osteopenia and osteoporosis (due to calcium and vitamin D malabsorption) and abnormal bleeding (malabsorption of vitamin K).
Diagnosis of the disease is complicated by the fact that the symptoms overlap with many other common diseases. However, patients of CD have increased levels of IgA anti-tissue transglutaminase (tTGA), and IgA anti-endomysium antibodies, and this feature is used for confirming the diagnosis. The only way to manage this disease is to switch to a gluten free diet. Symptoms ease within days of switching to this diet. However, in patients with severely damaged intestines, nutrients may have to be directly given through the blood until the villi heal.
CD is a genetic disease that runs in families. The disease has been shown to have a strong association with the HLA-DQ locus. Both HLA-DQA1 and HLA-DQB1 have been implicated in CD. It has been postulated that certain alleles at these loci may be involved in the production of receptors that bind very tightly to gliadin peptides, thereby activating T lymphocytes, and initiating the autoimmune response.
[See: Kuwait > Khuffash et al., 1987].
Khuffash et al. (1987) examined 20 Arab children suffering from Celiac disease (CD) in Kuwait (13 females and 7 males). Two subjects were monozygotic twin girls, four were female siblings coming from a family with 11 offsprings, and 13 subjects were Palestinians, 3 Kuwaitis, 2 Syrians, 1 Egyptian, and 1 Yemeni. The mean age of onset of symptoms in the studied group was 38 months, the mean age at the time of diagnosis was 72 months, the mean of delay was 38 months, and the incidence of CD in the examined region was 1:3000 births. The incidence of CD within subjects of Kuwaiti origin was found to be 1:6500 while in Palestinian subjects the incidence was 1:2400. Subjects were examined through collecting blood samples, multiple intestine biopsies, and duodenal aspirate for the inspection of Giardia. All patients demonstrated chronic diarrhea and slow growth, 16 patients showed abdominal distension, and 5 subjects experienced mood swings, rickets, and celiac crises (hypokalemia). Seven patients were excluded due to obtaining another etiology including Giardia, milk intolerance, and Campylobacter infection. Upon these results, the remaining patients underwent elimination of gluten from their diet which revealed an increase of growth during first year of gluten elimination, while the second biopsy demonstrated a histological remission in 7 patients and mild marginal improvement in 5 subjects. Five patients went through a third biopsy and experienced a clinical and histological relapse while the families of the three remaining children declined a third biopsy. Due to the complexity of identifying CD, Khuffash et al. (1987) believed that cautious long term follow-up of children presenting with chronic diarrhea, milk intolerance, and gastroenteritis syndromes will assist against failing to notice CD or over referrals.
Al-Tawaty and Elbargathy (1998) studied 243 children aged between 6 months and 18 years presenting with features suggestive of celiac disease to Al-Fateh Children's Hospital, Benghazi, Libya from 1976 to 1993. The diagnosis of celiac disease was made using the revised diagnostic criteria of the European Society of Pediatric Gastroenterology and Nutrition. Seventy-seven of the children conformed to these criteria. The male:female ratio was 1:1.3. Weight loss, anemia, anorexia, diarrhea and abdominal distention, in descending order of frequency, were the most frequently occurring clinical features.
In 2003, Ashabani et al. studied the occurrence of serologic markers in a group of Libyan children with positive clinical and histologic findings indicative of celiac disease diagnosis. Thirty-nine children with untreated celiac disease and 50 healthy school children, all younger than 14 years, were studied. Enzyme-linked immunosorbent assay for immunoglobulin G and immunoglobulin A (IgA) antigliadin, antitissue transglutaminase, and anticalreticulin antibodies was used to evaluate the serologic markers of the celiac patients. Immunoglobulin A antiendomysial antibodies were detected by indirect immunofluorescence using human umbilical cord tissue. Major clinical symptoms at presentation were weight loss (82%), abdominal distension (61.5%), diarrhea or steatorrhea (59%), pallor (41%), abdominal pain (20.5%), constipation (15%), vomiting (10%), and short stature (7.7%). Most of these symptoms disappeared after introduction of a gluten-free diet. Two years later, Ashabani et al. (2003) studied the occurrence of CD-related markers in a group of Libyan children with type 1 diabetes mellitus (DM). A cohort of 234 Libyan children with DM (121 males and 113 females) aged between 2 and 25 years and 50 healthy school children were screened for CD. Fifty patients (21.3%) were positive for IgA- and/or IgG-AGA, tTG, and anticalreticulin antibodies. Nineteen of these patients were EmA positive and seven were EmA negative. Ashabani et al. (2003) calculated the prevalence of CD in Libya as 10.3%; a value that is higher than in several European countries.
Majid et al. (2013) reported the first patient with comorbidity of primary sclerosing cholangitis and enteropathy-associated T-cell lymphoma. The patient was a 54-year-old man who stopped gluten-free diet after 15 years history of celiac disease. Majid et al. (2013) hinted that the prognosis in such case is remarkably very poor.
Fraser et al. (2003) studied the possibility of occult celiac disease being the cause of iron deficiency anemias by screening for anti tissue transglutaminase (tTg) and antiendomysial antibody (EMA) titres in 51 patients (43 females) of unexplained iron deficiency anemia. Serum from these patients was analyzed for IgG and IgA tTg antibodies and followed up by IgA EMA. Endoscopy and small bowel biopsy were then used to confirm the diagnosis in patients with positive serology. Two female patients had positive IgA EMA, and biopsy on one revealed subtotal villous atrophy, and accordingly gluten free diet was described to them. Fraser et al. (2004) being the first to report the use of EMA titres to screen occult celiac disease in the Arabian peninsula, concluded that occult celiac disease was present in Oman but masked by the fact that rice was the major dietary carbohydrate, and that it had the same prevalence as that occurring in UK (1/30 iron deficiency anemia patients and 1 in 200-300 of the general population), and that, therefore, it should be considered in any patient with unexplained iron deficiency anemia.
Between 1989 and 1999, 26 cases of celiac disease were handled in King Abdulaziz University Hospital; 38% of them were children who presented at a median age of 3.03 years with mainly gastrointestinal symptoms. As for adults, the median age at presentation was 31.3 years with a tendency to show extra-intestinal symptoms. More females were affected by this disease than males. Intriguingly, recorded cases in Arab adults were on the rise while the opposite trend was noted with children. Prevalence data from the Arab world were comparable to these from the west as reported by Akbar (2000). [Akbar DH. Celiac disease: pattern and trend comparison between Arab and Western population. Kuwait Med J. 2000; 32(4):378-81.]
Al-Aama et al. (2017) investigated the underlying genetic defect in a consanguineous Saudi family affected by Celiac Disease (CD). The 21-year-old female proband from this family suffered from type 1 diabetes mellitus. She and her younger sister both tested positive for endomysial antibodies and a CD diagnosis was confirmed by duodenal biopsy. Except for mild abdominal pain in the younger sister, neither patient had any other symptoms. Whole Exome Sequencing (WES) helped uncover a homozygous insertion c.1683_1684insATT, in the AK5 gene that segregated in an autosomal recessive manner in the family. However, further validation was carried out using 100 CD-affected Saudi patients and 100 healthy Saudi controls. Interestingly, the mutation was found to be highly penetrant in Saudi Arabs (Saudi MAF=0.62, ExAC MAF=0.000008) and was seen to modify the risk of the healthy Saudi population against CD development (p<0.002). This was further consolidated by in-silico analysis which predicted the mutation to induce a gain-of-function in the nucleoside phosphate kinase activity of AK5, potentially down-regulating CD4+ T-cell reactivity against gluten antigens. The authors hence stressed the importance of using population-specific variant databases to prevent false leads.