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Introduction Bacterial infections in CF patients are common and start early in life. The prognosis of the disease is substantially dependent on chronic respiratory infection and inflammation. Pseudomonas aeruginosa (PA) infection or chronic colonization have been established to cause a chronic decline in pulmonary function (PFT), and/or increase CF mortality. Objectives To obtain the prevalence of all bacterial pathogens in our CF patients and assess their evolution over time. Method A retrospective review of 327 patients with confirmed CF of all age groups, who had respiratory culture samples at the first visit and on a regular follow-up between January 1, 1990 and December 2018, was conducted. Results A total of 327 patients had a respiratory culture obtained at presentation. Two hundred and sixteen (66%) of 327 patients are alive, while 111 (34%) have died. Respiratory cultures were taken from nasopharyngeal aspiration (NPA) in 199 patients (61%), tracheal aspirate in 9 (3%), bronchoalveolar lavage (BAL)in one (0.29%), and in 124 patients (38%), sputum was induced. The eastern province contributed to the highest number of patients (122, 37.7%). There is a persistent increase in the prevalence of the common bacteria over the follow-up period of 7 years, namely Hemophilus influenzae (H. influenzae), Staphylococcus aureus (S. aureus), and all Pseudomonas (P. aeruginosa) culture types. Comparing cultures from the first and last follow-up visits, there was an increase in the prevalence of all (P. aeruginosa) cultures from 120 (34%) to 137 (53%), and a decrease in the prevalence of (S. aureus) and (H. influenzae) during the same follow-up period. Conclusion There is a progressive increase in the number of patients with the most pathogenic types of bacteria because of the advanced age at presentation. As more adult patients are enrolled, there is a need for improved awareness regarding the early eradication of pathogenic bacteria to prevent progressive pulmonary damage.

Introduction: Previous data showed that dental caries is common in the Saudi general population as well as in the Cystic fibrosis patients. Objectives: to identify the correlation of dental caries severity with cystic fibrosis (CFTR) gene mutations in a tertiary care center Methodology: Retrospective cohort study through reviewing medical files for cystic fibrosis patients who had dental assessment during the period January 1998 to December 2018. Results: A total of 56 patients in group 1 (less than 12 years of age) and 55 patients for group 2 (more than 12 years of age). The score for dental caries (decay, missing and filled teeth) dmft/DMFT were 4.85 (4.6) for group 1 and 5.94 (4.27) for group 2. There were 3 common mutations in both groups namely in c.3700A>G, c.1418delG and c.1911delG. There is another common mutation in group 1 located in c.579+1G>T. Additionally, group 2 has another 3 common mutations that included c.416A>T, c.3909C>G, and c.1647T>G. Almost 95 % of mutations are in homozygous state in both groups. There was no single mutation that favors deterioration in DFMT score. Almost all mutations have similar scores, but certainly, group 2 has worse DFMT compared to group 1. There was no difference in dmft/DMFT scores between homozygous and heterozygous CFTR in both groups. Conclusion: No identified mutation that correlates with worsening in dental caries scores. There was no difference in dental caries’ scores between homozygous and heterozygous CFTR in both pediatric and adult groups

Introduction Cystic fibrosis (CF) has been reported before in Saudi Arabia and the Gulf area. It has been found that screening for 10 most common cystic fibrosis transmembrane conductance regulator (CFTR) mutations can detect 80% of positive CFTR cases. Objectives To determine the geographic distribution of the most common CFTR variants in 5 regions of Saudi Arabia. Methodology A retrospective chart review of all CFTR variants conducted from January 1, 1992 to December 1, 2017. Results The ten most common CFTR mutations in the Saudi population were as follows: p.Gly473GlufsX54 (17%), p.Phe508del (12%), p.Ile1234Val (12%), 3120+1G > A (11%), 711+1G > T (9%), p.His139Leu (6%), p.Gln637Hisfs (5%), p.Ser549Arg (3%), p.N1303K (3%), and delExon19-21 (2%) along with other variants 79 (20%). In terms of the highest frequency, the c.2988+1G > A (3120+1G > A) variant was found in the eastern province (7.3%) of Saudi Arabia, the c.1418delG (p.Gly473GlufsX54) variant in the northern province (6.8%), the c.579+1G > T (711+1G > T) variant in the southern province (4.8%), the c.3700A > G (p.Ile1234Val) variant in the central province (4.8%), and c.1521_1523delCTT (p.Phe508del) variant in the western province (4.3%). Conclusion The eastern and the northern provinces have the highest prevalence of CF, with the c.2988+1G > A (3120+1G > A) and c.1418delG (p.Gly473GlufsX54) variants showing the highest distribution in the Saudi CF population, which may reflect the effect of consanguinity within the same tribe. Proper family screening and counseling should be emphasized.

Double homozygous mutation with the presence of double mutations in each allele is a very rare phenomenon with only 2 reports that have described this phenomenon in the medical literature.

Background Internationally, Cystic fibrosis-associated liver disease (CFLD) is considered the third leading cause of death, following lung disease and transplantation complications. Aims To identify the prevalence of CFLD in cystic fibrosis (CF) patients. Methodology A retrospective chart review for all patients with CF liver disease from a tertiary care center. Result A total of 341 CF patients were included. The mean age at the diagnosis of liver disease is 13.5 (7.6) years.The first elevated ALT was reported in 190/341 patients (56%), elevated AST in 124 patients (36%), elevated alkaline phosphatase (ALP) in 166 patients (49.1%), elevated GGT in 57 patients (23%), and elevated bilirubin in 24 patients (7%). There was an improvement of the liver enzyme values during the follow-up period, P-value = ( Conclusion Patients with CF should be screened early for liver enzymes, and should undergo the US study to detect liver disease at early stages and to prevent its progression.

Introduction Meconium ileus (MI) is one of the most common causes of intestinal obstruction in newborns. It is the earliest clinical manifestation of cystic fibrosis (CF). MI is suspected if a baby fails to pass meconium shortly after birth and develops symptoms of bowel obstruction, such as distention of the abdomen or vomiting. MI can lead to bowel perforation, a twisting of the bowel, or inflammation and infection of the abdominal cavity. Objectives To find the incidence and prevalence of meconium ileus in cystic fibrosis patients and to report on the most common gene mutation of MI in CF patients. Methodology Retrospective review of the medical documentations of all MI patients during the period of 1989–2018. Results A total of 40 CF confirmed patients were presented with MI. Twenty-nine patients (71%) are alive and 11 patients (29%) died or lost to follow-up. The following CFTR mutations were found: Eight patients (20%) with c.2988+1G>A; Intron 18. Seven patients (17.5%) with c.1418delG; Exon 11. Five patients (12.5%) with c.579+1G>T; Intron 5. Four patients (10%) with c.1911delG; Exon 14. Four patients (10%) with c.1521_1523delCTT; Exon 11. Four patients (10%) with c.416A>T; Exon 13. Three patients (7.5%) with c.2421A>G; Exon 14. Two patients (5%) with c.3908A>C; Exon 21. One patient (2.5%) with c.3889dupT; Exon 24. One patient (2.5%) with c.1657C>T; Exon 12. One patient (2.5%) with c.2547C>A; Exon 14a. Eighteen patients (45%) were presented with vomiting, 38 patients (95%) had postnatal radiological findings, 7 patients (17.5%) had electrolytes imbalance. Five patients (12.5%) had cholestasis and 4 patients (10%) developed chronic liver disease. Thirty-five patients (79.5%) underwent surgical repair and 9 patients (20.5%) were treated medically. Mean age of operation was 2.25 (2) days. Of 9 patients, 6 (66.6%) were treated with gastrograffin enema, 2 patients (22.2%) with oral N-acetylcysteine and 1 patient (11.1%) with saline rectal wash. Thirteen patients (31.5%) required TPN. Five patients had recurrent operation. Conclusion CF and meconium ileus are commonly present in CF patients in Saudi Arabia. Prognosis is similar to other CFs without MI, if treated early. Thirty percent of our CF/MI patients have intronic mutations.

Introduction Celiac disease (CD) has been described before in Saudi Arabia (SA) to be at the range of 1%–2% in the general population, but the association of celiac disease and cystic fibrosis (CF) has never been described before in the Middle East. Objectives To describe the prevalence of the association of CD and CF in patients with gastrointestinal symptomatology in a tertiary care center. Method ology: A retrospective charts review of all confirmed CD and CF patients for the years 1989–2018. Results In a total of 391 confirmed CF patients, 74 of them (19%) had celiac screening due to their symptomatology in the form of (abdominal pain and distension, vomiting, diarrhea despite adequate pancreatic enzyme replacements, and had high antigliadin antibodies and anti-transglutaminase IgA (tTGA). Thirty-five of the 74 patients were male (47.3%, and 39 (52.7%) were female patients. The mean age at diagnosis of CD was 6.1 (3.9), and the mean age at follow up was 7 (5 years). Only 2 of the 74 patients (3%) had bowel biopsies with the typical pathological findings of CD with villous atrophy. Both patients were placed on a gluten-free diet and showed marked improvement in symptomatology and weight gain. Conclusion CD screening should be considered in all CF patients despite the absence of symptoms. The prevalence of CD in CF patients in SA is similar to or slightly higher than that of the general population. A further study to screen the whole CF population is needed to delineate the actual prevalence, particularly in nonsymptomatic CF.

BACKGROUND: Cystic fibrosis (CF) occurs in populations in Saudi Arabia and the Gulf area. Approximately 2000 known variants have been identified for the CF transmembrane conductance regulator (CTFR) gene. Screening for ten of the most common variants can detect 80% of alleles. OBJECTIVE: Determine the pattern of CFTR variants in the CF population of Saudi Arabia. DESIGN: A retrospective, descriptive. SETTING: Tertiary care center. PATIENTS AND METHODS: We examined the medical records of 396 confirmed CF patients of all age groups that were positive for a CFTR variant from the period of 1 January 1998 to 1 December 2017. MAIN OUTCOME MEASURES: Zygosity, morbidity and mortality patterns of different types of CFTR variants. SAMPLE SIZE: 312 families that included 396 patients. RESULTS: Of 48 variants identified, 6 were novel, having not been described in the medical literature. A homozygous state was found in 283 families (90.7%) and compound heterozygosity in 23 (7.4%). Six families were heterozygous (1.9%). Median age (interquartile range) was 10.2 months (4.4 months to 5.7 years) at diagnosis and 9.7 (5.4-16.5) years at follow up. Of 396 patients, 378 patients (95.5%) survived and 18 (4.5%) died. The ten most common variants identified in descending frequency were: p.Gly473GlufsX54 in 98 alleles (16%), p.Ile1234Val in 66 alleles (11%), F508del in 64 alleles (11%), 711+1G>T in 62 alleles (10%), 3120+1G>A in 62 alleles (11%), p.His139Leuin 38 alleles (6.4%), p.Gln637Hisfs in 30 alleles (5.2%), p.Ser549Arg in 27 alleles (4.5%), p.Asn1303Lys in 14 alleles (2.3%), delExon19-21in 10 alleles (1.6%). This analysis identified 79.2% of our CFTR variants. CONCLUSION: CFTR mutational patterns in our CF population are characterized by a high allelic heterogeneity. The high prevalence of homozygous variants reflects the high level of consanguinity between parents. LIMITATIONS: Our CFTR screening reflected only about 80% of CF patients in Saudi Arabia. CONFLICT OF INTEREST: None.

Cardiac catheterization is important in the diagnosis and risk stratification of pulmonary hypertensive vascular disease (PHVD) in children. Acute vasoreactivity testing provides key information about management, prognosis, therapeutic strategies, and efficacy. Data obtained at cardiac catheterization continue to play an important role in determining the surgical options for children with congenital heart disease and clinical evidence of increased pulmonary vascular resistance. The Pediatric and Congenital Heart Disease Task Forces of the Pulmonary Vascular Research Institute met to develop a consensus statement regarding indications for, conduct of, acute vasoreactivity testing with, and pitfalls and risks of cardiac catheterization in children with PHVD. This document contains the essentials of those discussions to provide a rationale for the hemodynamic assessment by cardiac catheterization of children with PHVD.

Cystic fibrosis (CF) is a lethal, monogenic disorder that affects multiple organ systems of the body. The incidence has been described before in the Middle East to be 1 in 2000 to 1 in 5800 live births, and the median survival was estimated to be from 10 to 20 years of age.The present article attempts to revisit various facets of this disease and specifically highlights the most important lacunae that exist in treating CF. In addition, it also tries to emphasize the steps in improving the median survival of patients with CF, in these countries.

We report the results of clinical exome sequencing (CES) on >2,200 previously unpublished Saudi families as a first-tier test. The predominance of autosomal-recessive causes allowed us to make several key observations. We highlight 155 genes that we propose to be recessive, disease-related candidates. We report additional mutational events in 64 previously reported candidates (40 recessive), and these events support their candidacy. We report recessive forms of genes that were previously associated only with dominant disorders and that have phenotypes ranging from consistent with to conspicuously distinct from the known dominant phenotypes. We also report homozygous loss-of-function events that can inform the genetics of complex diseases. We were also able to deduce the likely causal variant in most couples who presented after the loss of one or more children, but we lack samples from those children. Although a similar pattern of mostly recessive causes was observed in the prenatal setting, the higher proportion of loss-of-function events in these cases was notable. The allelic series presented by the wealth of recessive variants greatly expanded the phenotypic expression of the respective genes. We also make important observations about dominant disorders; these observations include the pattern of de novo variants, the identification of 74 candidate dominant, disease-related genes, and the potential confirmation of 21 previously reported candidates. Finally, we describe the influence of a predominantly autosomal-recessive landscape on the clinical utility of rapid sequencing (Flash Exome). Our cohort’s genotypic and phenotypic data represent a unique resource that can contribute to improved variant interpretation through data sharing.

To identify factors that contributed to morbidity and mortality of cystic fibrosis (CF) population in the Kingdom of Saudi Arabia (KSA).This retrospective chart review was carried out in King Faisal Specialist Hospital and Research Centre, Riyadh, KSA, during a 9 year period, November 1993 to November 2002, on confirmed CF patients, for demographic, clinical and mortality data.A total of 190 CF patients were diagnosed during the 9 years. One hundred and sixty-four (86%) patients are alive, 26 (14%) died. Ninety-nine (52%) were males and 91 (48%) were females. Age at diagnosis 2.8 3.5 years, and period of follow up 3 3 years. In 80% of patients, symptoms started1 year of age. Sixty-five percent of patients were in the mild to moderate malnutrition stage (90th percentile), and 63% are in the mild to moderate stunted growth (90th percentile). Factors that contributed to early mortality are: calculated weight/height (p-value 0.01), low albumin level at follow up (0.001), high hematocrit (HCT) (p-values=0.0002), low mean corpuscular volume (MCV) (p-0.0002), low mean corpuscular hemoglobin concentration (MCHC) (p-value 0.001), early development of antibiotic resistance (p-value=0.01).High HCT, low MCV, low MCHC and low albumin are factors related to poor prognosis and early death in CF patients. Iron supplement should be given to these patients even in the presence of normal hemoglobin. Early nutritional rehabilitation is needed to improve survival of our CF patients. Cohort isolation should be encouraged in CF centres. Early treatment of chronic pseudo colonization should be adopted to improve survival.

OBJECTIVE: This study was conducted to review the etiological factors and diseases associated with pediatric noncystic fibrosis bronchiectasis in a tertiary care center in Saudi Arabia. MATERIALS AND METHODS: A retrospective review of all patients with confirmed noncystic fibrosis (Non-CF) bronchiectasis by chest X-ray and/or CT chest in a pulmonary clinic during the period 1993–2005 at a tertiary care center in Riyadh. RESULTS: A total of 151 cases were diagnosed as Non-CF bronchiectasis. Seventy-five (49.7%) were male, 76 (50.3%) were female; 148 (98%) are alive and 3 (2%) died. The southwestern regions constituted 72 (50%) of the cases. There was a period of (5 ± 3.2) years between the start of symptoms and diagnosis of bronchiectasis. More than two-thirds of the patients had cough, tachypnea, wheezing, sputum production and failure to thrive. Ninety-one (60%) had associated diseases: Pulmonary diseases in 48 (32%), immunodeficiency in 27 (18%), central nervous system anomalies in 10 (7%), cardiac in 10 (7%) and asthma in 103 (68%) of the patients. Left lower lobe was commonly involved in 114 (76%) patients. Sixty-eight (67%) were found to have sinusitis. More than two-thirds of patients had two or more associated diseases. Forty-nine (32%) developed gastroesophageal reflux. Hemophilus influenza was cultured in 56 (37%), strept pneumoniae in 25 (17%) and pseudomonas aeruginosa in 24 (16%) of the patients. Eighty percent of the patients who had pulmonary function test had abnormal changes. Disease progression was related to development of symptoms before 5 years of age, persistent atelectasis and right lower lobe involvement (P< 0.05). CONCLUSION: Non-CF bronchiectasis should be included in the differential diagnosis of recurrent chest infection in Saudi Arabia. Early diagnosis and identification of associated diseases is needed to prevent progression of the disease.

Standardization of the diagnostic routine for children with congenital heart disease associated with pulmonary arterial hypertension (PAH-CHD) is crucial, in particular since inappropriate assignment to repair of the cardiac lesions (e.g., surgical repair in patients with elevated pulmonary vascular resistance) may be detrimental and associated with poor outcomes. Thus, members of the Congenital Heart Disease and Pediatric Task Forces of the Pulmonary Vascular Research Institute decided to conduct a survey aimed at collecting expert opinion from different institutions in several countries, covering many aspects of the management of PAH-CHD, from clinical recognition to noninvasive and invasive diagnostic procedures and immediate postoperative support. In privileged communities, the vast majority of children with congenital cardiac shunts are now treated early in life, on the basis of noninvasive diagnostic evaluation, and have an uneventful postoperative course, with no residual PAH. However, a small percentage of patients (older at presentation, with extracardiac syndromes or absence of clinical features of increased pulmonary blood flow, thus suggesting elevated pulmonary vascular resistance) remain at a higher risk of complications and unfavorable outcomes. These patients need a more sophisticated diagnostic approach, including invasive procedures. The authors emphasize that decision making regarding operability is based not only on cardiac catheterization data but also on the complete diagnostic picture, which includes the clinical history, physical examination, and all aspects of noninvasive evaluation.