INTRODUCTION: The etiology of bronchiectasis may be idiopathic in up to one half of adults. Consideration of Primary Ciliary Dyskinesia (PCD) may not be considered in adults without dextrocardia. We present a subject with bronchiectasis with PCD and central pair absence, a rare variant of PCD not previously diagnosed at such a late age.
CASE PRESENTATION: A 37-year-old recent immigrant from Pakistan presented to the Chest Clinic with recurrent upper and lower respiratory tract infection which he had for many years, decreased exercise tolerance, weight loss, fatigue, and night sweats. He was a current smoker of 3-4 cigarettes/day . He had chronic hepatitis C and complained of anosmia. He had no allergies, no alcohol or drug use, and denied any family history of similar problems. He has one son with mental retardation. His pulmonary function revealed moderate obstruction with normal total lung capacity and diffusion. Clinical examination revealed a gentleman with wheezing at all visits with a chronic cough. A CT scan revealed bronchiectasis predominant in the right middle lobe and less in both lower lobes. Sputum for AFB smear and culture were negative for TB. HIV infection, cystic fibrosis, and alpha-1 antitrypsin deficiency were ruled out and work-up for collagen vascular diseases was negative including a negative ANA and RF. His total immunoglobulins IgG, IgA, IgM, and IgE levels were normal except for subclass analysis of IgG-4 levels which were slightly low. He has been managed with smoking cessation (he has quit for over 1 year), and has been treated intermittently with different antibiotic regimens with sputum cultures growing out multi-drug resistant Pseudomonas, Aspergillus Fumigatus, and Mycobacterium mucogenicum. He also is on inhaled steroid and bronchodilators to try to minimize his chronic wheezing. In order to try to make a more definitive diagnosis he was referred to ENT and had both maxillary sinus drainage and nasal epithelial biopsy to rule out primary ciliary dyskinesia (PCD). Electron microscopy revealed ciliary cross sections with absence of the central doublet/microtubule pair consistent with PCD with central pair absence(1).
DISCUSSION: PCD is a ciliopathy that is associated with an array of ultrastructural defects of cilia. This genetic disorder is primarily autosomal recessive and is seen in about 1:15-30,000 live births (1,2). Cases of PCD can be grouped into dynein arm defects (78-96%) and central ciliary defects (4-22%). Central ciliary defects, as seen in this case, are not associated with defects in laterality whereas more then 50% of PCD patients have laterality defects and up to 50% have Kartagener’s syndrome (dextrocardia, sinusitis, bronchiectasis). Genetic linkage studies have revealed heterozygous nonsense mutations in radial spoke head protein genes, probably RSPH9 and RSPH4A, causing PCD with the central microtubular defect as seen here (2). Interestingly, ciliary beat frequency can be normal, but beat pattern can be circular instead of the normal forward-backward motion. Our patient was also noted to have heterogeneous ultrastructural abnormalities of some peripheral microtubules, consistent with acquired defects related to recurrent airway damage. It is unknown if IgG-4 subclass deficiency is related to PCD.
CONCLUSIONS: Adults with recurrent sinopulmonary infections and idiopathic bronchiectasis should be considered for evaluation of PCD. The presence of fertility and absence of typical features, like childhood presentation, situs inversus, family history, and infertility do not exclude the possibility of PCD. PCD with central pair abnormality, although rare, is not associated with laterality defects and this is the first reported case of this specific abnormality detected at such a late age. Definitive detection of causes of bronchiectasis will lead to better understanding of disease processes, facilitate patient management, and impact on potential decisions regarding the possibility of lung transplants.
Reference #1 Papon JF, Coste A, et. al. A 20-year experience of electron microscopy in the diagnosis of primary ciliary dyskinesia. Eur Respir J 2010;35:1057-63.
Reference #2 Castleman, VH, Romio L, et al.Mutations in Radial Spoke Head Protein Genes RSPH9 and RSPH4A Cause Primary Ciliary Dyskinesia with Central-Microtubular-Pair Abnormalities. Am Journal of Human Genetics 2009;84(2):197-209.
DISCLOSURE: The following authors have nothing to disclose: Sikander Zulqarnain, Gene Pesola
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