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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 = (<0.05).Ultrasound liver assessments were performed in 258/341 patients (75.7%). One hundred and twelve patients (43%) had abnormal findings. In 14 patients (5.4%), assessment exhibited advanced liver disease (liver cirrhosis and periportal fibrosis). Out of 190 patients, who were given ursodeoxycholic acid for elevated liver enzymes, 180 (94.7%) exhibited improvement. One patient underwent liver transplant at the age of 12. Four patients were submitted for liver biopsy; periportal fibrosis was observed in 4 patients (1.6%), and liver cirrhosis by ultrasound (US) in 10 patients (4%). 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.
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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.
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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.