A 29-Year-Old Man With Type 2 Hermansky-Pudlak Syndrome and Wolff-Parkinson-White Syndrome: The Hypothesis of a Potential Link Between These Two Conditions.

Abstract

A 29-year-old Moroccan with oculocutaneous albinism presented with a history of exertional dyspnea, recurrent epistaxis, and bacterial infections, raising suspicion of Hermansky-Pudlak syndrome (HPS). Further evaluation revealed neutropenia, impaired platelet function, pulmonary fibrosis, and mild pulmonary hypertension. An ECG identified ventricular pre-excitation with a postero-septal right accessory pathway, consistent with Wolff-Parkinson-White (WPW) syndrome. Genetic testing confirmed a homozygous mutation in the AP3B1 gene and a diagnosis of Type 2 HPS (HPS-2) was made. HPS-2 is an extremely rare disorder, and to our knowledge, the co-occurrence of WPW syndrome has not been previously reported in literature. We propose a potential causal link between these two conditions, as mutations in the AP3B1 gene-which encodes the beta subunit of the adapter protein 3 trafficking complex-result in mistrafficking of transmembrane proteins from the endosomal and trans-Golgi network to lysosomes and endosome-lysosome-related organelles. Specifically, the dysfunction of a transmembrane protein, namely the lysosome-associated membrane protein 2 (LAMP-2), has been implicated in the development of cardiac accessory pathways, as seen in Danon disease. We hypothesize that individuals with HPS-2 may have a genetic predisposition to WPW syndrome, and this hypothesis should be investigated in further studies.