PP25 GENETICALLY CONFIRMED PRIMARY CILIARY DYSKINESIA (PCD) IN MALAYSIA

Mariana Daud, 
Paediatric Respiratory Unit, Hospital Raja Perempuan Zainab11 (HRPZ11), Kota Bharu, Kelantan

Objective:

Primary ciliary dyskinesia (PCD) is a rare inherited disease characterized by motile cilia malfunction with varied clinical and genetic profile. Clinical symptoms include left-right lateralization, infertility, and chronic respiratory illness. Diagnosis of PCD requires combinations of tests, including nasal brushing, nasal nitric oxide (nNO) and genetic analysis.The purpose of this study was to clarify the clinical profile of Malaysian patients with genetically confirmed PCD, and investigate the nNO level and the common mutations in these patients. 

Methods:

A retrospective chart review of PCD patients was performed at Paediatric Respiratory Clinic, HRPZ11,Kelantan who had Whole Exon Sequencing (WES) done at 3billion Laboratory, South Korea between  October-December 2021. Data on the demographic profile, situs/laterality status, PrImary CiliARy DyskinesiA Rule (PICADAR) score, nNO concentration, and thoracic high resolution computed tomography scan findings were collected. 

Results:

Seven patients (5 females) were diagnosed with PCD. Age at diagnosis was between 1 to 24 years (median, 12 years). Respiratory and nasal symptoms were the most common complaint (100% each), followed by aural (42.9%) symptoms. Situs inversus was present in 3 (42.9%) cases. None had congenital cardiac anomalies.The median interval from suspected to confirmed PCD was 2.8 years. The mean PICADAR score was 8.2. Majority (85.7% ) of patients had bronchiectasis at diagnosis of PCD.The mean nNO level was 20.5 ppb  (7-32ppb)(PCD reference:< 171 ppb). The common mutations identified were CCNO in 4/7  patients (57.1%),followed by DNAAF11 in 2/7 patients (28.6%), and DNAAF4 in 1/7(14.3%). All the mutated genes were associated with Autosomal Recessive (AR) PCD, but  no history of consanguinity in the affected family.

Conclusion:

Common mutated gene in Malaysian patients with PCD are Autosomal Recessive CCNO mutation.All patients except one (technically infeasible for nNO testing) have markedly low nNO. Situs inversus with a high PICADAR score should have a high index of suspicion of PCD.