Clinical Profile of Georgian Pediatric Cystic Fibrosis Patients with 1677delTA Mutation
DOI:
https://doi.org/10.52340/GBMN.2025.01.01.135Keywords:
1677delTA mutation, CFTR, cystic fibrosis, Georgia, pancreatic insufficiency, Pseudomonas AeruginosaAbstract
Background: Cystic fibrosis (CF) is an autosomal recessive disease caused by CFTR mutations leading to multisystem involvement. The 1677delTA mutation, rare globally but common in Georgia, is associated with severe disease. Objectives: We aimed to characterize the clinical features, pancreatic status, growth outcomes, and Pseudomonas aeruginosa colonization in Georgian pediatric CF patients carrying the 1677delTA mutation. Methods: A retrospective review of 90 pediatric CF patients registered in the National Rare Diseases Program was conducted. Genotypes, pancreatic elastase, growth parameters (CDC percentiles), P. aeruginosa colonization (Leeds criteria), and distal intestinal obstruction syndrome (DIOS) were analyzed. Results: Among 90 patients, 24 (26.7%) were homozygous and 32 (35.6%) heterozygous for 1677delTA. Median age at diagnosis was <1 year, with over half identified through newborn screening (NBS). Severe pancreatic insufficiency predominated (80% in homozygotes, 70% in heterozygotes), while 10-20% showed intermediate or sufficient function. Growth was generally preserved: 50-55% had BMI within the normal range. Chronic P. aeruginosa infection occurred in 20% of homozygotes and 25% of heterozygotes; DIOS was observed in ~10%. The most frequent accompanying mutations were D110H, E92K, W1282X, and F508del. Conclusions: The 1677delTA mutation is highly prevalent in Georgian pediatric CF patients and is typically associated with severe pancreatic insufficiency and early-onset disease. Genotype-guided management is essential to optimize outcomes, provide individualized care, and guide national CF policies. The observed sibling cases highlight the consistent disease pattern within families and reinforce the importance of early diagnosis and tailored management. Access to CFTR modulators could offer therapeutic benefits for heterozygous patients when available.References
Sputum culture (average 4/year);
Fecal pancreatic elastase was assessed at diagnosis and re-evaluated during follow-up in patients who retained pancreatic sufficiency until the onset of insufficiency;
Anthropometry: weight, height, BMI, and percentile charts (using CDC growth charts);
Classification of Pseudomonas aeruginosa colonization: chronic (Leeds criteria: more than 50% of sputum cultures over one year positive for Pseudomonas), acute (isolated in the following 3 months), ever-present (any previous isolation);
Genotypes, pancreatic function, age at diagnosis, and colonization status.
Two siblings homozygous for 1677delTA, aged 16 and 11 years, both with severe pancreatic insufficiency and BMI 21.9 and 17.3, respectively; neither had DIOS or Pseudomonas colonization;
Two siblings homozygous for 1677delTA, aged 14 and 16 years, both with severe pancreatic insufficiency and BMI 18.2 and 17.6; one had DIOS (score 2), neither had Pseudomonas colonization;
Two siblings heterozygous for 1677delTA and I1234V, aged 16 and 13 years, both with severe pancreatic insufficiency and chronic Pseudomonas colonization (first isolation at 14 and 10 years). Another sibling from the same family carried Leu997Phe/Ile1234Val, 11 years old, diagnosed at 2 years;
Two siblings heterozygous for 1677delTA and E92K, aged 14 and 8 years, both with intermediate pancreatic insufficiency and BMI 15.0 and 16.0; neither had DIOS or Pseudomonas colonization;
Two siblings heterozygous for 1677delTA and F508del, aged 10 and 5 years, both with severe pancreatic insufficiency; the younger sibling had Pseudomonas colonization at 1 year, and neither had DIOS.
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