Ciliary function analysis for the diagnosis of primary ciliary dyskinesia:Advantages of ciliogenesis in culture

The gold standard fur the diagnosis of primary ciliary dyskinesia (PCD) is a dynein deficiency shown with transmission electron microscopy. However, t here are many cases of PCD without dynein deficiency. When considering cili ary function, there are similar problems of sensitivity in diagnosis and th ere is also a major lack of specificity. Based on the normal ciliary functi on and ultrastructure and the absence of secondary abnormalities after cili ogenesis in sequential monolayer-suspension culture, the diagnostic value o f ciliary function analysis after ciliogenesis was investigated in more tha n 70 PCD and 640 non-PCD cases. In biopsies, ciliary immotility was found i n 66% of PCD casts but was also found in 8% of non-PCD cases. PCD was later confirmed in 61% of the biopsies with ciliary immotility. Normal ciliary b eat frequency (CBF) was Found in 20% of PCD biopsies. Coordinated ciliary a ctivity was observed in 10% of PCD cases. After ciliogenesis in culture, ci liary immotility was present in 78% of the PCD cases but never in non-PCD c ases. CBF was normal after ciliogenesis in 7% of the PCD cases and was alwa ys found in non-PCD cases. Absence of coordinated ciliary activity was foun d in 100% of PCD cases and 0% of non-PCD cases. In conclusion, while ciliar y function analysis in a biopsy never proves, nor excludes the diagnosis of PCD, after ciliogenesis in culture CBF measurement can be diagnostic for P CD and reaches 100% specificity and sensitivity when considering coordinate d ciliary activity, making it the single 100% diagnostic parameter for PCD.