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J Pediatr Genet 2022; 11(03): 236-239
DOI: 10.1055/s-0040-1717136
Case Report

Importance of Immediate Thiamine Therapy in Children with Suspected Thiamine-Responsive Megaloblastic Anemia—Report on Two Patients Carrying a Novel SLC19A2 Gene Mutation

Anita Spehar Uroic
1   Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics, University Hospital Centre Zagreb, Zagreb, Croatia
,
Dragan Milenkovic
2   Varnamo Hospital, Varnamo, Sweden
,
Elisa De Franco
3   Molecular Genetics, University of Exeter Medical School, Exeter, United Kingdom
,
Ernest Bilic
4   Department of Pediatrics, University Hospital Centre Zagreb, Medical School, University of Zagreb, Zagreb, Croatia
,
Natasa Rojnic Putarek
5   Medical School, Juraj Dobrila Univeristy of Pula, Pula, Croatia
,
Nevena Krnic
4   Department of Pediatrics, University Hospital Centre Zagreb, Medical School, University of Zagreb, Zagreb, Croatia
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Abstract

Thiamine-responsive megaloblastic anemia (TRMA) is an autosomal recessive disorder characterized by the development of megaloblastic anemia, diabetes mellitus, and sensorineural deafness. We report on the first two Croatian patients with TRMA, compound heterozygotes for nonsense, c.373C > T; p.(Gln125Ter) and novel missense variant, c.1214C > G; p.(Thr405Arg) in SLC19A2 gene. The first was diagnosed at 4 months with diabetes mellitus and severe anemia requiring transfusions. As TRMA was suspected, thiamine therapy was immediately started to prevent further transfusions and insulin therapy. His brother developed extreme anemia at 3 weeks of age while waiting for the results of the genetic test. Severe anemia in this sibling may have been prevented if thiamine had been initiated earlier.

Keywords

thiamine-responsive megaloblastic anemia - neonatal diabetes mellitus - SLC19A2 gene


Publication History

Received: 27 June 2020

Accepted: 26 August 2020

Article published online:
08 October 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
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  • References

  • 1 Porter FS, Rogers LE, Sidbury Jr JB. Thiamine-responsive megaloblastic anemia. J Pediatr 1969; 74 (04) 494-504
    CrossrefPubMedGoogle Scholar
  • 2 Shaw-Smith C, Flanagan SE, Patch AM. et al. Recessive SLC19A2 mutations are a cause of neonatal diabetes mellitus in thiamine-responsive megaloblastic anaemia. Pediatr Diabetes 2012; 13 (04) 314-321
    CrossrefPubMedGoogle Scholar
  • 3 Bergmann AK, Sahai I, Falcone JF. et al. Thiamine-responsive megaloblastic anemia: identification of novel compound heterozygotes and mutation update. J Pediatr 2009; 155 (06) 888-892.e1
    CrossrefPubMedGoogle Scholar
  • 4 Liberman MC, Tartaglini E, Fleming JC, Neufeld EJ. Deletion of SLC19A2, the high affinity thiamine transporter, causes selective inner hair cell loss and an auditory neuropathy phenotype. J Assoc Res Otolaryngol 2006; 7 (03) 211-217
    CrossrefPubMedGoogle Scholar
  • 5 Habeb AM, Flanagan SE, Zulali MA. International Neonatal Diabetes Consortium. et al. Pharmacogenomics in diabetes: outcomes of thiamine therapy in TRMA syndrome. Diabetologia 2018; 61 (05) 1027-1036
    CrossrefPubMedGoogle Scholar
  • 6 Kipioti A, George ND, Hoffbrand AV, Sheridan E. Cone-rod dystrophy in thiamine-responsive megaloblastic anemia. J Pediatr Ophthalmol Strabismus 2003; 40 (02) 105-107
    CrossrefPubMedGoogle Scholar
  • 7 Meire FM, Van Genderen MM, Lemmens K, Ens-Dokkum MH. Thiamine-responsive megaloblastic anemia syndrome (TRMA) with cone-rod dystrophy. Ophthalmic Genet 2000; 21 (04) 243-250
    CrossrefPubMedGoogle Scholar
  • 8 Ricketts CJ, Minton JA, Samuel J. et al. Thiamine-responsive megaloblastic anaemia syndrome: long-term follow-up and mutation analysis of seven families. Acta Paediatr 2006; 95 (01) 99-104
    CrossrefPubMedGoogle Scholar
  • 9 Potter K, Wu J, Lauzon J, Ho J. Beta cell function and clinical course in three siblings with thiamine-responsive megaloblastic anemia (TRMA) treated with thiamine supplementation. J Pediatr Endocrinol Metab 2017; 30 (02) 241-246
    CrossrefPubMedGoogle Scholar
  • 10 Onal H, Bariş S, Ozdil M. et al. Thiamine-responsive megaloblastic anemia: early diagnosis may be effective in preventing deafness. Turk J Pediatr 2009; 51 (03) 301-304
    PubMedGoogle Scholar
  • 11 Mikstiene V, Songailiene J, Byckova J. et al. Thiamine responsive megaloblastic anemia syndrome: a novel homozygous SLC19A2 gene mutation identified. Am J Med Genet A 2015; 167 (07) 1605-1609
    CrossrefPubMedGoogle Scholar
  • 12 European Commission, Health & Consumer Protection Directorate-General. Opinion of the Scientific Committee on Food on the Tolerable Upper Intake Level of Vitamin B1 Official report. 2001 , Accessed August 6, 2020 at: https://ec.europa.eu/food/sites/food/files/safety/docs/sci-com_scf_out93_en.pdf
    PubMedGoogle Scholar