From a reproductive specialist to a pulmonologist, or a Long path to diagnosis: clinical observations

Diagnosis of many inherited diseases, particularly primary ciliary dyskinesia and cystic fibrosis (CF), remains inadequate. These diseases are often detected late in the course of infertility evaluation. The aim is to describe two clinical observations of male infertility with late detection of hereditary respiratory tract diseases. Methods. Two male patients, aged 33 and 32 years, with primary marital infertility due to total or subtotal asthenoteratozoospermia were studied. A comprehensive clinical examination, CT of the chest and paranasal sinuses, standard spermatological examination, electron microscopic examination of spermatozoa and nasal epithelial cells, CFTR gene sequencing, whole exome sequencing, and direct automated Sanger sequencing were performed. Results. Based on the results of a comprehensive genetic, pulmonological, andrological, and electron microscopic examination, both patients were diagnosed with autosomal recessive monogenic diseases associated with respiratory damage and primary male infertility. The patient with total asthenoteratozoospermia was diagnosed with primary ciliary dyskinesia (PCD) associated with probable pathogenic variants in the DRC1 gene, while the patient with obstructive azoospermia was diagnosed with a pancreatic-insufficient of cystic fibrosis caused by two pathogenic variants in the CFTR gene. Conclusion. The presented clinical cases demonstrate a prolonged diagnostic search in patients associated with an unpronounced clinical picture, lack of detailed anamnesis and appropriate investigations.