Mitochondrial diseases in Hong Kong: prevalence, clinical characteristics and genetic landscape

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.

Keywords: Hong Kong; Mitochondrial diseases; Prevalence.

Fig. 1

Distribution of Mitochondrial syndromes (total 74). The absolute number of cases are shown in parentheses. Abbreviations: CPEO Chronic progressive external ophthalmoplegia, KSS Kearns Sayre syndrome, LHON Leber hereditary optic neuropathy, MEGDEL 3-methylglutaconic aciduria, deafness, encephalopathy, and Leigh-like disease, MELAS Mitochondrial Encephalopathy, lactic acidosis, and stroke-like episodes, MERRF Myoclonus Epilepsy with ragged red fibers, MIDD Maternally Inherited Diabetes and Deafness

Fig. 2

Distribution of mitochondrial DNA pathogenic variants (total 72). The absolute number of cases are shown in parentheses. Others (1.4%/1 patient each): m.10197G>A, m.11778G>A, m.8622delC, m.3946G>A, m.13052G>A. Within these mtDNA pathogenic variants, m.3946G>A, m.13094T>C, and m.13052G>A are not included in the hotspots analyses in several public hospitals. MtDNA deletion also cannot be tested by hotspot analyses. Therefore, total 12 patients (16.7% of total) cannot be identified by hotspot analyses alone

Fig. 3

Distribution of nuclear DNA pathogenic variants (total 38). The absolute number of cases are shown in parentheses. Others (2.7%/1 patient each): CHKB, COQ7, GTPBP3, LDHD, NDUFAF5, NDUFA9, NDUFS3, SERAC1