1. Genotype/phenotype correlations of childhood‐onset congenital sideroblastic anaemia in a European cohort
- Author
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Guy Leverger, Marie-Amelyne Le Rouzic, Christian Rose, Laila Hessissen, Nadja Jäkel, Bertrand Isidor, Stéphane Ducassou, Patrick Lutz, Sophie Bayart, Cyrielle Fouquet, Mony Fahd, Emmanuelle Bourrat, Marlène Pasquet, Fanny Fouyssac, Mohamed Touati, Isabelle Thuret, Thierry Leblanc, Christiane Vermylen, Ralf Knoefler, Sandrine Marlin, Thomas Matthes, Valerie Triolo, Emmanuel Raffoux, Jean-Pierre Vannier, and Caroline Kannengiesser
- Subjects
Male ,medicine.medical_specialty ,genotype phenotype correlation ,Mitochondrial Membrane Transport Proteins ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Germline mutation ,Diabetes mellitus ,Internal medicine ,Genotype ,medicine ,Humans ,congenital sideroblastic anaemia ,Child ,Genetic Association Studies ,Immunodeficiency ,Retrospective Studies ,ddc:616 ,Thrombocytosis ,business.industry ,Genetic Diseases, X-Linked ,Hematology ,medicine.disease ,Nucleotidyltransferases ,Phenotype ,Anemia, Sideroblastic ,Europe ,iron overload ,030220 oncology & carcinogenesis ,Mutation ,Cohort ,Female ,business ,5-Aminolevulinate Synthetase ,030215 immunology ,Rare disease - Abstract
Congenital sideroblastic anaemia (CSA) is a rare disease caused by germline mutations of genes involved in haem and iron-sulphur cluster formation, and mitochondrial protein biosynthesis. We performed a retrospective multicentre European study of a cohort of childhood-onset CSA patients to explore genotype/phenotype correlations. We studied 23 females and 20 males with symptoms of CSA. Among the patients, the most frequently mutated genes were ALAS2 (n = 10; 23·3%) and SLC25A38 (n = 8; 18·6%), causing isolated forms of microcytic anaemia of varying severity. Five patients with SLC19A2 mutations suffered from thiamine-responsive megaloblastic anaemia and three exhibited the 'anaemia, deafness and diabetes' triad. Three patients with TRNT1 mutations exhibited severe early onset microcytic anaemia associated with thrombocytosis, and two exhibited B-cell immunodeficiency, inflammatory syndrome and psychomotor delay. The prognoses of patients with TRNT1 and SLC2A38 mutations were generally dismal because of comorbidities or severe iron overload. No molecular diagnosis could be established in 14/43 cases. This study emphasizes the frequency of ALAS2 and SLC25A38 mutations and provides the largest comprehensive analysis to date of genotype/phenotype correlations in CSA. Further studies of CSA patients with data recorded in an international registry would be helpful to improve patient management and establish standardized guidelines.
- Published
- 2019