Valentina Bravatà1, Luigi Minafra1, Graziella Callari2, Cecilia Gelfi3, Luigi Maria Edoardo Grimaldi4. 1. Istituto di bioimmagini e fisiologia molecolare CNR-LATO, Cefalù PA, Scilly, Italy. 2. U.O. Neurologia, Fondazione Istituto "San Raffaele-G. Giglio", Cefalù PA, Scilly, Italy. 3. Istituto di bioimmagini e fisiologia molecolare CNR-LATO, Cefalù PA, Scilly, Italy; Department of Biomedical Sciences for Health, University of Milan, Milan, Italy. 4. U.O. Neurologia, Fondazione Istituto "San Raffaele-G. Giglio", Cefalù PA, Scilly, Italy. Electronic address: Luigi.grimaldi@hsr.it.
Abstract
OBJECTIVE: Thiamine or vitamin B1 deficiency diminishes thiamine-dependent enzymatic activity, alters mitochondrial function, impairs oxidative metabolism, and causes selective neuronal death. We analyzed for the first time, the role of all known mutations within three specific thiamine carrier genes, SLC19 A2, SLC19 A3, and SLC25 A19, in a patient with atrophic beriberi, a multiorgan nutritional disease caused by thiamine deficiency. METHODS: A 44-year-old male alcoholic patient from Morocco developed massive bilateral leg edema, a subacute sensorimotor neuropathy, and incontinence. Despite normal vitamin B1 serum levels, his clinical picture was rapidly reverted by high-dose intramuscular thiamine treatment, suggesting a possible genetic resistance. We used polymerase chain reaction followed by amplicon sequencing to study all the known thiamine-related gene mutations identified within the Human Gene Mutation Database. RESULTS: Thirty-seven mutations were tested: 29 in SLC19 A2, 6 in SLC19 A3, and 2 in SLC25 A19. Mutational analyses showed a wild-type genotype for all sequences investigated. CONCLUSION: This is the first genetic study in beriberi disease. We did not detect any known mutation in any of the three genes in a sporadic dry beriberi patient. We cannot exclude a role for other known or unknown mutations, in the same genes or in other thiamine-associated genes, in the occurrence of this nutritional neuropathy.
OBJECTIVE:Thiamine or vitamin B1 deficiency diminishes thiamine-dependent enzymatic activity, alters mitochondrial function, impairs oxidative metabolism, and causes selective neuronal death. We analyzed for the first time, the role of all known mutations within three specific thiamine carrier genes, SLC19 A2, SLC19 A3, and SLC25 A19, in a patient with atrophic beriberi, a multiorgan nutritional disease caused by thiamine deficiency. METHODS: A 44-year-old male alcoholic patient from Morocco developed massive bilateral leg edema, a subacute sensorimotor neuropathy, and incontinence. Despite normal vitamin B1 serum levels, his clinical picture was rapidly reverted by high-dose intramuscular thiamine treatment, suggesting a possible genetic resistance. We used polymerase chain reaction followed by amplicon sequencing to study all the known thiamine-related gene mutations identified within the Human Gene Mutation Database. RESULTS: Thirty-seven mutations were tested: 29 in SLC19 A2, 6 in SLC19 A3, and 2 in SLC25 A19. Mutational analyses showed a wild-type genotype for all sequences investigated. CONCLUSION: This is the first genetic study in beriberi disease. We did not detect any known mutation in any of the three genes in a sporadic dry beriberi patient. We cannot exclude a role for other known or unknown mutations, in the same genes or in other thiamine-associated genes, in the occurrence of this nutritional neuropathy.
Authors: María Del Milagro Teran; Alejandra de Moreno de LeBlanc; Graciela Savoy de Giori; Jean Guy LeBlanc Journal: Appl Microbiol Biotechnol Date: 2021-02-06 Impact factor: 4.813
Authors: Valentina Bravatà; Luigi Minafra; Giusi I Forte; Francesco P Cammarata; Michele Saporito; Filippo Boniforti; Domenico Lio; Maria C Gilardi; Cristina Messa Journal: BMC Res Notes Date: 2015-02-04