Abstract
Background
Several metabolic disorders follow an autosomal recessive inheritance pattern. Epidemiological information on these disorders is usually limited in develo** countries. Our objective is to assess carrier frequencies of rare autosomal recessive metabolic diseases in a cohort of Brazilian patients that underwent molecular investigation with exome sequencing and estimate the overall frequency of these diseases using the Hardy–Weinberg equation.
Methods and results
We reviewed the molecular findings of 320 symptomatic patients who had carrier status for recessive diseases actively searched. A total of 205 rare variants were reported in 138 different genes associated with metabolic diseases from 156 patients, which represents that almost half (48.8%) of the patients were carriers of at least one heterozygous pathogenic/likely pathogenic (P/LP) variant for rare metabolic disorders. Most of these variants are harbored by genes associated with multisystemic involvement. We estimated the overall frequency for rare recessive metabolic diseases to be 10.96/10,000 people, while the frequency of metabolic diseases potentially identified by newborn screening was estimated to be 2.93/10,000.
Conclusions
This study shows the potential research utility of exome sequencing to determine carrier status for rare metabolic diseases, which may be a possible strategy to evaluate the clinical and social burden of these conditions at the population level and guide the optimization of health policies and newborn screening programs.
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All authors provided the conception and design of the study, acquisition of data, analysis and interpretation of data, drafting the article, revised it critically for important intellectual content and final approval of the version to be submitted.
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The following authors are employees (received salary and other bonuses) of Fleury Medicina e Saude: CRDCQ, CHC, SFP, APD, CMM. Author CAK declares no financial interests.
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This study was performed in line with the principles of the Declaration of Helsinki. This study was granted ethics committee approval from Fleury Group and Faculdade de Medicina da Universidade de São Paulo (Plataforma Brasil; CAAE# 02617018.3.0000.5474; Fleury# 3.372.339).
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Quaio, C.R.D.A.C., Moreira, C.M., Chung, C.H. et al. Frequency of carriers for rare metabolic diseases in a Brazilian cohort of 320 patients. Mol Biol Rep 49, 3911–3918 (2022). https://doi.org/10.1007/s11033-022-07241-3
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DOI: https://doi.org/10.1007/s11033-022-07241-3