• Something wrong with this record ?

Pharmacogenomics in diabetes: outcomes of thiamine therapy in TRMA syndrome

AM. Habeb, SE. Flanagan, MA. Zulali, MA. Abdullah, R. Pomahačová, V. Boyadzhiev, LE. Colindres, GV. Godoy, T. Vasanthi, R. Al Saif, A. Setoodeh, A. Haghighi, A. Haghighi, Y. Shaalan, . , AT. Hattersley, S. Ellard, E. De Franco,

. 2018 ; 61 (5) : 1027-1036. [pub] 20180215

Language English Country Germany

Document type Journal Article, Observational Study, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc19012832
E-resources Online Full text

NLK ProQuest Central from 1999-01-01 to 1 year ago
Medline Complete (EBSCOhost) from 2000-01-01 to 1 year ago
Health & Medicine (ProQuest) from 1999-01-01 to 1 year ago
Public Health Database (ProQuest) from 1999-01-01 to 1 year ago

Links

PubMed 29450569
DOI 10.1007/s00125-018-4554-x
Knihovny.cz E-resources

AIMS/HYPOTHESIS: Diabetes is one of the cardinal features of thiamine-responsive megaloblastic anaemia (TRMA) syndrome. Current knowledge of this rare monogenic diabetes subtype is limited. We investigated the genotype, phenotype and response to thiamine (vitamin B1) in a cohort of individuals with TRMA-related diabetes. METHODS: We studied 32 individuals with biallelic SLC19A2 mutations identified by Sanger or next generation sequencing. Clinical details were collected through a follow-up questionnaire. RESULTS: We identified 24 different mutations, of which nine are novel. The onset of the first TRMA symptom ranged from birth to 4 years (median 6 months [interquartile range, IQR 3-24]) and median age at diabetes onset was 10 months (IQR 5-27). At presentation, three individuals had isolated diabetes and 12 had asymptomatic hyperglycaemia. Follow-up data was available for 15 individuals treated with thiamine for a median 4.7 years (IQR 3-10). Four patients were able to stop insulin and seven achieved better glycaemic control on lower insulin doses. These 11 patients were significantly younger at diabetes diagnosis (p = 0.042), at genetic testing (p = 0.01) and when starting thiamine (p = 0.007) compared with the rest of the cohort. All patients treated with thiamine became transfusion-independent and adolescents achieved normal puberty. There were no additional benefits of thiamine doses >150 mg/day and no reported side effects up to 300 mg/day. CONCLUSIONS/INTERPRETATION: In TRMA syndrome, diabetes can be asymptomatic and present before the appearance of other features. Prompt recognition is essential as early treatment with thiamine can result in improved glycaemic control, with some individuals becoming insulin-independent. DATA AVAILABILITY: SLC19A2 mutation details have been deposited in the Decipher database ( https://decipher.sanger.ac.uk/ ).

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc19012832
003      
CZ-PrNML
005      
20190411104524.0
007      
ta
008      
190405s2018 gw f 000 0|eng||
009      
AR
024    7_
$a 10.1007/s00125-018-4554-x $2 doi
035    __
$a (PubMed)29450569
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a gw
100    1_
$a Habeb, Abdelhadi M $u Paediatric Department, Prince Mohammed bin Abdulaziz Hospital, National Guard Ministry, P.O. Box 40740, Al Madinah, 41511, Kingdom of Saudi Arabia. amhabeb@hotmail.com.
245    10
$a Pharmacogenomics in diabetes: outcomes of thiamine therapy in TRMA syndrome / $c AM. Habeb, SE. Flanagan, MA. Zulali, MA. Abdullah, R. Pomahačová, V. Boyadzhiev, LE. Colindres, GV. Godoy, T. Vasanthi, R. Al Saif, A. Setoodeh, A. Haghighi, A. Haghighi, Y. Shaalan, . , AT. Hattersley, S. Ellard, E. De Franco,
520    9_
$a AIMS/HYPOTHESIS: Diabetes is one of the cardinal features of thiamine-responsive megaloblastic anaemia (TRMA) syndrome. Current knowledge of this rare monogenic diabetes subtype is limited. We investigated the genotype, phenotype and response to thiamine (vitamin B1) in a cohort of individuals with TRMA-related diabetes. METHODS: We studied 32 individuals with biallelic SLC19A2 mutations identified by Sanger or next generation sequencing. Clinical details were collected through a follow-up questionnaire. RESULTS: We identified 24 different mutations, of which nine are novel. The onset of the first TRMA symptom ranged from birth to 4 years (median 6 months [interquartile range, IQR 3-24]) and median age at diabetes onset was 10 months (IQR 5-27). At presentation, three individuals had isolated diabetes and 12 had asymptomatic hyperglycaemia. Follow-up data was available for 15 individuals treated with thiamine for a median 4.7 years (IQR 3-10). Four patients were able to stop insulin and seven achieved better glycaemic control on lower insulin doses. These 11 patients were significantly younger at diabetes diagnosis (p = 0.042), at genetic testing (p = 0.01) and when starting thiamine (p = 0.007) compared with the rest of the cohort. All patients treated with thiamine became transfusion-independent and adolescents achieved normal puberty. There were no additional benefits of thiamine doses >150 mg/day and no reported side effects up to 300 mg/day. CONCLUSIONS/INTERPRETATION: In TRMA syndrome, diabetes can be asymptomatic and present before the appearance of other features. Prompt recognition is essential as early treatment with thiamine can result in improved glycaemic control, with some individuals becoming insulin-independent. DATA AVAILABILITY: SLC19A2 mutation details have been deposited in the Decipher database ( https://decipher.sanger.ac.uk/ ).
650    _2
$a alely $7 D000483
650    _2
$a megaloblastová anemie $x farmakoterapie $x genetika $7 D000749
650    _2
$a předškolní dítě $7 D002675
650    _2
$a kohortové studie $7 D015331
650    _2
$a diabetes mellitus $x farmakoterapie $x genetika $7 D003920
650    _2
$a ženské pohlaví $7 D005260
650    _2
$a genetické testování $7 D005820
650    _2
$a genotyp $7 D005838
650    _2
$a percepční nedoslýchavost $x farmakoterapie $x genetika $7 D006319
650    _2
$a lidé $7 D006801
650    _2
$a kojenec $7 D007223
650    _2
$a mužské pohlaví $7 D008297
650    _2
$a membránové transportní proteiny $x genetika $7 D026901
650    _2
$a mutace $7 D009154
650    12
$a farmakogenetika $7 D010597
650    _2
$a fenotyp $7 D010641
650    _2
$a průzkumy a dotazníky $7 D011795
650    _2
$a thiamin $x terapeutické užití $7 D013831
650    _2
$a nedostatek thiaminu $x vrozené $x farmakoterapie $x genetika $7 D013832
655    _2
$a časopisecké články $7 D016428
655    _2
$a pozorovací studie $7 D064888
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Flanagan, Sarah E $u Institute of Biomedical and Clinical Science, University of Exeter Medical School, Royal Devon and Exeter Hospital, Barrack Road, Exeter, EX2 5DW, UK.
700    1_
$a Zulali, Mohamed A $u Paediatric Department, College of Medicine, Taibah University, Madinah, Kingdom of Saudi Arabia.
700    1_
$a Abdullah, Mohamed A $u Paediatric Department, Khartoum University, Khartoum, Sudan.
700    1_
$a Pomahačová, Renata $u Department of Paediatrics, Charles University, Medical Faculty and University Hospital Pilsen, Pilsen, Czech Republic.
700    1_
$a Boyadzhiev, Veselin $u Medical University, Varna, Bulgaria.
700    1_
$a Colindres, Lesby E $u Hospital María De Especialidades Pediatricas, Tegucigalpa, Honduras.
700    1_
$a Godoy, Guillermo V $u Hospital María De Especialidades Pediatricas, Tegucigalpa, Honduras.
700    1_
$a Vasanthi, Thiruvengadam $u Kanchi Kamakoh Child Trust Hospital, Chennai, India.
700    1_
$a Al Saif, Ramlah $u Paediatric Department, Maternity and Children's Hospital, Dammam, Kingdom of Saudi Arabia.
700    1_
$a Setoodeh, Aria $u Growth & Development Research Centre, University of Tehran, Medical Sciences, Tehran, Iran.
700    1_
$a Haghighi, Amirreza $u Toronto General Hospital, University of Toronto, Toronto, ON, Canada.
700    1_
$a Haghighi, Alireza $u Department of Genetics and Medicine, Harvard Medical School, Boston, MA, USA. Broad Institutes of Harvard and MIT, Cambridge, MA, USA. Partners HealthCare Laboratory for Molecular Medicine, Cambridge, MA, USA.
700    1_
$a Shaalan, Yomna $u Faculty of Medicine, Cairo University, Cairo, Egypt.
700    1_
$a ,
700    1_
$a Hattersley, Andrew T $u Institute of Biomedical and Clinical Science, University of Exeter Medical School, Royal Devon and Exeter Hospital, Barrack Road, Exeter, EX2 5DW, UK.
700    1_
$a Ellard, Sian $u Institute of Biomedical and Clinical Science, University of Exeter Medical School, Royal Devon and Exeter Hospital, Barrack Road, Exeter, EX2 5DW, UK.
700    1_
$a De Franco, Elisa $u Institute of Biomedical and Clinical Science, University of Exeter Medical School, Royal Devon and Exeter Hospital, Barrack Road, Exeter, EX2 5DW, UK. e.de-franco@exeter.ac.uk.
773    0_
$w MED00001391 $t Diabetologia $x 1432-0428 $g Roč. 61, č. 5 (2018), s. 1027-1036
856    41
$u https://pubmed.ncbi.nlm.nih.gov/29450569 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20190405 $b ABA008
991    __
$a 20190411104541 $b ABA008
999    __
$a ok $b bmc $g 1392142 $s 1051137
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2018 $b 61 $c 5 $d 1027-1036 $e 20180215 $i 1432-0428 $m Diabetologia (Berlin) $n Diabetologia $x MED00001391
LZP    __
$a Pubmed-20190405

Find record

Citation metrics

Archiving options