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Genotype/phenotype correlations of childhood‐onset congenital sideroblastic anaemia in a European cohort
Author(s) -
Fouquet Cyrielle,
Le Rouzic MarieAmelyne,
Leblanc Thierry,
Fouyssac Fanny,
Leverger Guy,
Hessissen Laila,
Marlin Sandrine,
Bourrat Emmanuelle,
Fahd Mony,
Raffoux Emmanuel,
Vannier JeanPierre,
Jäkel Nadja,
Knoefler Ralf,
Triolo Valerie,
Pasquet Marlene,
Bayart Sophie,
Thuret Isabelle,
Lutz Patrick,
Vermylen Christiane,
Touati Mohamed,
Rose Christian,
Matthes Thomas,
Isidor Bertrand,
Kannengiesser Caroline,
Ducassou Stephane
Publication year - 2019
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.16100
Subject(s) - medicine , compound heterozygosity , cohort , genotype , thrombocytosis , pediatrics , gastroenterology , phenotype , genetics , gene , biology , platelet
Summary 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.