AACG Oral 4: PREVALENCE AND NATURAL HISTORY OF RESPIRATORY CHAIN DISORDERS IN A 10-YEAR BIRTH COHORT

摘要

Background: Mitochondrial respiratory chain disorders (RCD) comprise over 200 monogenic disorders; however, well-defined pe-diatric population-based studies are scarce. Aim: To describe the natural history of childhood-onset RC disorders. Methods: One-hundred-twelve patients with a definite diagnosis by Bernier criteria (91 with molecular diagnoses), born in South East Australia between 1987 and 1996 with onset by age 16 years, were included. Analyses were conducted using Excel 2017, SPSS v19, and Prism 7. Results: Age of onset ranged from 0 to 165.5 months. Male:female ratio was 1.3 (p = .078). The minimum birth prevalence per 100,000 (MBP) was estimated overall to be 6.56 (95% CI [5.45, 7.90]), 1.7(95% CI [1.18, 2.44]) for mitochondrial (mt) DNA mutations and 3.63 (95% CI [2.83, 4.66]) for nuclear mutations. The most common clinical syndrome was Leigh (-like) (n = 38, MBP 2.23, 95% CI [1.62, 3.06]) followed by Alpers and childhood myocerebrohepatopathy disorders (n = 14, MBP 0.82,95% CI [0.49,1.38]). Median survival was longer for mtDNA than nuclear mutations (322 vs. 27 months and 25 months for unknown genetic defect; p = .0007). Median survival within the mtDNA group was longer for tRNA genes than protein encoding genes (322 vs. 38 months). Discussion: The MBP is comparable with our previously published estimate of 6.2 (from 43 patients born between 1991 and 1994). This larger cohort provides estimates for the prevalence of nuclear and mtDNA mutations and important natural history information. Conclusion: This study highlights the wide clinical heterogeneity of RCD and provides natural history data, which illustrate how stratification by molecular and clinical phenotype can contribute to genetic counseling, surveillance, and resource allocation.