Abnormal profiles of cathepsin C secreted in urine of Papillon Lefevre syndrome patients.

BACKGROUND: Papillon Lefevre syndrome (PLS) is an autosomal recessive disorder that results from a mutated gene that encodes a lysosomal peptidase known as cathepsin C (CTSC). The clinical presentation of PLS involves mainly palmoplantar keratosis and periodontitis with a variable degree of severity. SUBJECTS: and methods: Our study included ten patients with a broad spectrum of palmoplantar keratosis and periodontitis severity. CTSC variants were detected by Sanger sequencing. CTSC protein secreted in urine was detected by western blotting. RESULTS: Five patients have missense variants, Four have nonsense variants, and one has splice variants in CTSC. The activation products of cathepsin C protein (Heavy and light chains) were absent in all patients' urine samples except one with a significantly reduced level compared to the controls. The dimeric form of CTSC protein was found in all the studied cases. The monomeric form was found in five cases. The products of proteolytic activation of CTSC by other cathepsins (L and S) were found in the urine samples of five of the patients. Each patient had a characteristic pattern of accumulated CTSC protein maturation/activation substrates, intermediates, and products. 40% of the patients had the activation products of other lysosomal cathepsins. CONCLUSION: Urinary CTSC in PLS patients could be used as a diagnostic biomarker for the biochemical screening of the disease. Different variants in CTSC result in different profiles of CTSC secreted in the urine of PLS patients. The profiles of secreted CTSC in urine could be correlated to the severity of palmoplantar keratosis.

Could Congenital Insensitivity to Pain with Anhidrosis Be Misdiagnosed as Papillon-Lefèvre Syndrome?

Papillon-Lefèvre syndrome (PLS) is a rare autosomal recessive disorder characterized by early loss of teeth with hyperkeratosis of the palms and soles. Congenital insensitivity to pain with anhidrosis (CIPA) is a disorder of decreased pain sensation, decreased sweating, recurrent infections, and fever. Here, we report a 5-year-old girl born to consanguineous parents with a family history of a similarly affected sibling. The girl presented with early loss of teeth and palmoplantar hyperkeratosis, hence, provisionally diagnosed as PLS. Further clinical examination and detailed history taking shifted the diagnosis to CIPA. CIPA could be misdiagnosed as PLS. Congenital insensitivity to pain with anhidrosis, although rare, should be considered in the differential diagnosis of PLS.