Mitochondrial diseases in Hong Kong: prevalence, clinical characteristics and genetic landscape
Authors: Wong Tsz-sum , Belaramani Kiran M. , Chan Chun-kong , Chan Wing-ki , Chan Wai-lun Larry , Chang Shek-kwan , Cheung Sing-ngai , Cheung Ka-yin , Cheung Yuk-fai , Chong Shuk-ching Josephine , Chow Chi-kwan Jasmine , Chung Hon-yin Brian , Fan Sin-ying Florence , Fok Wai-ming Joshua , Fong Ka-wing , Fung Tsui-hang Sharon , Hui Kwok-fai , Hui Ting-hin , Hui Joannie , Ko Chun-hung , Kwan Min-chung , Kwok Mei-kwan Anne , Kwok Sung-shing Jeffrey , Lai Moon-sing , Lam Yau-on , Lam Ching-wan , Lau Ming-chung , Law Chun-yiu Eric , Lee Wing-cheong , Lee Han-chih Hencher , Lee Chin-nam , Leung Kin-hang , Leung Kit-yan , Li Siu-hung , Ling Tsz-ki Jacky , Liu Kam-tim Timothy , Lo Fai-man , Lui Hiu-tung , Luk Ching-on , Luk Ho-ming , Ma Che-kwan , Ma Karen , Ma Kam-hung , Mew Yuen-ni , Mo Alex , Ng Sui-fun , Poon Wing-kit Grace , Rodenburg Richard , Sheng Bun , Smeitink Jan , Szeto Cheuk-ling Charing , Tai Shuk-mui , Tse Choi-ting Alan , Tsung Li-yan Lilian , Wong Ho-ming June , Wong Wing-yin Winnie , Wong Kwok-kui , Wong Suet-na Sheila , Wong Chun-nei Virginia , Wong Wai-shan Sammy , Wong Chi-kin Felix , Wu Shun-ping , Wu Hiu-fung Jerome , Yau Man-mut , Yau Kin-cheong Eric , Yeung Wai-lan , Yeung Hon-ming Jonas , Yip Kin-keung Edwin , Young Pui-hong Terence , Yuan Gao , Yuen Yuet-ping Liz , Yuen Chi-lap , Fung Cheuk-wing 
Published: March 2023

Abstract
Objective
To determine the prevalence of mitochondrial diseases (MD) in Hong Kong (HK) and to evaluate the clinical characteristics and genetic landscape of MD patients in the region.

Methods
This study retrospectively reviewed the phenotypic and molecular characteristics of MD patients from participating public hospitals in HK between January 1985 to October 2020. Molecularly and/or enzymatically confirmed MD cases of any age were recruited via the Clinical Analysis and Reporting System (CDARS) using relevant keywords and/or International Classification of Disease (ICD) codes under the HK Hospital Authority or through the personal recollection of treating clinicians among the investigators.

Results
A total of 119 MD patients were recruited and analyzed in the study. The point prevalence of MD in HK was 1.02 in 100,000 people (95% confidence interval 0.81–1.28 in 100,000). 110 patients had molecularly proven MD and the other nine were diagnosed by OXPHOS enzymology analysis or mitochondrial DNA depletion analysis with unknown molecular basis. Pathogenic variants in the mitochondrial genome (72 patients) were more prevalent than those in the nuclear genome (38 patients) in our cohort. The most commonly involved organ system at disease onset was the neurological system, in which developmental delay, seizures or epilepsy, and stroke-like episodes were the most frequently reported presentations. The mortality rate in our cohort was 37%.

Conclusion
This study is a territory-wide overview of the clinical and genetic characteristics of MD patients in a Chinese population, providing the first available prevalence rate of MD in Hong Kong. The findings of this study aim to facilitate future in-depth evaluation of MD and lay the foundation to establish a local MD registry.