BACKGROUND Cystic fibrosis (CF) is the most common, life-threatening, autosomal-recessive disorder among Caucasians. To date, approximately 2000 mutations in the CFTR gene have been reported. Some of these mutations are very rare, and some represent individual sequence changes in the gene. The introduction of newborn screening (NBS) in high prevalence countries for CF has considerably changed the diagnosing of this metabolic disease. Currently, in most cases, a diagnosis is made based on NBS, including or expanded with DNA analysis and confirmed with sweat chloride tests, rather than waiting until the child has already developed signs and symptoms. However, in rare cases, NBS does not provide enough information to confirm or reject a CF diagnosis. Not only are there small groups of patients who have false-negative or false-positive NBS results, but there is also a growing number of patients with positive NBS results in whom results of sweat tests and genetic examinations do not provide definite conclusions. Despite all knowledge and modern diagnostic tools at our disposal, sometimes the clinical presentation is so inconclusive, that making a final diagnosis remains a challenge. CASE PRESENTATION In this case report, we present a male infant of Polish origin, whose symptoms and laboratory findings (including metabolic acidosis) were strongly suggestive of metabolic disease other than cystic fibrosis. Newborn screening for CF was positive, but the first sweat test results were equivocal, and initial and extended molecular tests were negative. Finally, after considering broad differential diagnosis, introducing treatment specific for CF and excluding other metabolic diseases, a third expanded genetic test revealed the presence of a rare pathogenic mutation in both alleles of the CFTR gene: c.4035_4038dupCCTA (p.Ser1347ProfsX13). CONCLUSION Although CF is considered a monogenic disorder, the relationship between genotype and phenotype is very complex. The reported case shows the unusual presentation of the disease. The patient's clinical symptoms and laboratory findings, in combination with molecular test results, provide useful information for further observing the genotype-phenotype correlations in cystic fibrosis.

中文翻译：

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纯合患者罕见CFTR突变的囊性纤维化临床表现罕见：一例。

背景技术囊性纤维化（CF）是高加索人中最常见，威胁生命的常染色体隐性遗传疾病。迄今为止，已经报道了CFTR基因中大约2000个突变。这些突变中的一些非常罕见，有些代表基因中各个序列的变化。在高发国家，CF的新生儿筛查（NBS）的引入极大地改变了这种代谢疾病的诊断。当前，在大多数情况下，诊断是基于NBS进行的，包括或通过DNA分析进行诊断，并通过汗液氯化物检测进行确认，而不是等到孩子已经出现体征和症状后再进行诊断。但是，在极少数情况下，NBS无法提供足够的信息来确认或拒绝CF诊断。不仅有少数患者的NBS结果为假阴性或假阳性，但是，越来越多的NBS结果呈阳性的患者无法通过汗液测试和基因检查得出明确的结论。尽管我们掌握了所有知识和现代诊断工具，但有时临床表现尚无定论，因此最终诊断仍然是一个挑战。病例介绍在本病例报告中，我们介绍了一名波兰籍男婴，其症状和实验室检查结果（包括代谢性酸中毒）强烈提示除囊性纤维化以外的其他代谢性疾病。新生儿CF筛查为阳性，但首次出汗测试结果不明确，初始和扩展分子测试均为阴性。最后，在考虑了广泛的鉴别诊断之后，引入了针对CF的治疗方法，并排除了其他代谢性疾病，第三次扩展的基因测试揭示了CFTR基因的两个等位基因c.4035_4038dupCCTA（p.Ser1347ProfsX13）中都存在罕见的致病突变。结论尽管CF被认为是一种单基因疾病，但基因型和表型之间的关系非常复杂。报告的病例显示出该疾病的异常表现。患者的临床症状和实验室检查结果与分子检测结果相结合，为进一步观察囊性纤维化的基因型与表型相关性提供了有用的信息。报告的病例显示出该疾病的异常表现。患者的临床症状和实验室检查结果与分子检测结果相结合，为进一步观察囊性纤维化的基因型与表型相关性提供了有用的信息。报告的病例显示出该疾病的异常表现。患者的临床症状和实验室检查结果与分子检测结果相结合，为进一步观察囊性纤维化的基因型与表型相关性提供了有用的信息。