Three siblings with thiamine-responsive megaloblastic anemia (TRMA) with a homozygous c.454delGGCATinsAT mutation in SLC19A2 are described. The index case presented at 14 months’ old with severe non-ketotic hyperglycemia, dehydration, seizures and sinovenous thrombosis. She was started on insulin and developed sensorineural hearing loss around 2 years old. Two siblings were found to have the same mutation and were started on thiamine. One sibling developed transient hyperglycemia after several years of thiamine supplementation of 12 mg/kg that resolved with an increased thiamine dose (23 mg/kg). A younger sibling continues to remain diabetes-free on thiamine (24 mg/kg). The clinical course in this family suggests that there is an effect of thiamine on pancreatic beta cell function in patients with TRMA given the resolution of impaired fasting glucose with increasing thiamine dose in one sibling and the lack of diabetes to date in the siblings that were treated early with thiamine.
We are grateful to the family of our patients who have agreed to share their children’s stories.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
1. Maassen JA. Mitochondrial diabetes, diabetes and the thiamine-responsive megaloblastic anaemia syndrome and MODY-2. Diseases with common pathophysiology? Panminerva Med 2002;44:295–300.Search in Google Scholar
2. Scharfe C, Hauschild M, Klopstock T, Janssen AJ, Heidemann PH, et al. A novel mutation in the thiamine responsive megaloblastic anaemia gene SLC19A2 in a patient with deficiency of respiratory chain complex I. J Med Genet 2000;37:669–73.10.1136/jmg.37.9.669Search in Google Scholar
3. Meire FM, Van Genderen MM, Lemmens K, Ens-Dokkum MH. Thiamine-responsive megaloblastic anemia syndrome (TRMA) with cone-rod dystrophy. Ophthalmic Genet 2000;21:243–50.10.1076/1381-6810(200012)2141-HFT243Search in Google Scholar
4. Yilmaz Agladioglu S, Aycan Z, Bas VN, Peltek Kendirci HN, Onder A. Thiamine-responsive megaloblastic anemia syndrome: a novel mutation. Genet Couns 2012;23:149–56.Search in Google Scholar
5. Ricketts CJ, Minton JA, Samuel J, Ariyawansa I, Wales JK, et al. Thiamine-responsive megaloblastic anaemia syndrome: long-term follow-up and mutation analysis of seven families. Acta Paediatr 2006;95:99–104.10.1111/j.1651-2227.2006.tb02188.xSearch in Google Scholar
6. Bappal B, Nair R, Shaikh H, Al Khusaiby SM, de Silva V. Five years followup of diabetes mellitus in two siblings with thiamine responsive megaloblastic anemia. Indian Pediatr 2001;38:1295–8.Search in Google Scholar
7. Gritli S, Omar S, Tartaglini E, Guannouni S, Fleming JC, et al. A novel mutation in the SLC19A2 gene in a Tunisian family with thiamine-responsive megaloblastic anaemia, diabetes and deafness syndrome. Br J Haematol 2001;113:508–13.10.1046/j.1365-2141.2001.02774.xSearch in Google Scholar PubMed
8. Villa V, Rivellese A, Di Salle F, Iovine C, Poggi V, et al. Acute ischemic stroke in a young woman with the thiamine-responsive megaloblastic anemia syndrome. J Clin Endocrinol Metab 2000;85:947–9.10.1210/jcem.85.3.6419Search in Google Scholar PubMed
9. Mozzillo E, Melis D, Falco M, Fattorusso V, Taurisano R, et al. Thiamine responsive megaloblastic anemia: a novel SLC19A2 compound heterozygous mutation in two siblings. Pediatr Diabetes 2013;14:384–7.10.1111/j.1399-5448.2012.00921.xSearch in Google Scholar PubMed
10. Pichler H, Zeitlhofer P, Dworzak MN, Diakos C, Haas OA, et al. Thiamine-responsive megaloblastic anemia (TRMA) in an Austrian boy with compound heterozygous SLC19A2 mutations. Eur J Pediatr 2012;171:1711–5.10.1007/s00431-012-1730-8Search in Google Scholar PubMed
11. Ganie MA, Ali I, Ahangar AG, Wani MM, Ahmed S, et al. Thiamine responsive megaloblastic anemia syndrome associated with patent ductus arteriosus: First case report from Kashmir Valley of the Indian subcontinent. Indian J Endocrinol Metab 2012;16:646–50.10.4103/2230-8210.98033Search in Google Scholar PubMed PubMed Central
12. Bergmann AK, Sahai I, Falcone JF, Fleming J, Bagg A, et al. Thiamine-responsive megaloblastic anemia: identification of novel compound heterozygotes and mutation update. J Pediatr 2009;155:888–92 e1.10.1016/j.jpeds.2009.06.017Search in Google Scholar PubMed PubMed Central
13. Alzahrani AS, Baitei E, Zou M, Shi Y. Thiamine transporter mutation: an example of monogenic diabetes mellitus. Eur J Endocrinol 2006;155:787–92.10.1530/eje.1.02305Search in Google Scholar PubMed
14. Ganesh R, Ezhilarasi S, Vasanthi T, Gowrishankar K, Rajajee S. Thiamine responsive megaloblastic anemia syndrome. Indian J Pediatr 2009;76:313–4.10.1007/s12098-009-0058-5Search in Google Scholar
15. Pomero F, Allione A, Molinar Min A, La Selva M, Porta M. Thiamine, beta-cell function and peripheral glucose utilization in thiamine-responsive megaloblastic anemia (TRMA) syndrome. Acta Diabetol 2000;37:103.10.1007/s005920070027Search in Google Scholar
16. Bouyahia O, Ouderni M, Ben Mansour F, Matoussi N, Khaldi F. Diabetic acido-ketosis revealing thiamine-responsive megaloblastic anemia. Ann Endocrinol (Paris) 2009;70:477–9.10.1016/j.ando.2009.09.001Search in Google Scholar
17. Kurtoglu S, Hatipoglu N, Keskin M, Kendirci M, Akcakus M. Thiamine withdrawal can lead to diabetic ketoacidosis in thiamine responsive megaloblastic anemia: report of two siblings. J Pediatr Endocrinol Metab 2008;21:393–7.10.1515/JPEM.2008.21.4.393Search in Google Scholar
18. Beshlawi I, Al Zadjali S, Bashir W, Elshinawy M, Alrawas A, et al. Thiamine responsive megaloblastic anemia: the puzzling phenotype. Pediatr Blood Cancer 2014;61:528–31.10.1002/pbc.24849Search in Google Scholar
19. Finkel L, Piantino J, Goldstein J, Wainwright MS. Venous stroke and status epilepticus due to milk-induced anemia in a child. Pediatr Emerg Care 2015;31:129–31.10.1097/PEC.0000000000000306Search in Google Scholar
20. Aissi D, Dennis J, Ladouceur M, Truong V, Zwingerman N, et al. Genome-wide investigation of DNA methylation marks associated with FV Leiden mutation. PLoS One 2014;9:e108087.10.1371/journal.pone.0108087Search in Google Scholar
21. Heit JA, Armasu SM, Asmann YW, Cunningham JM, Matsumoto ME, et al. A genome-wide association study of venous thromboembolism identifies risk variants in chromosomes 1q24.2 and 9q. J Thromb Haemost 2012;10:1521–31.10.1111/j.1538-7836.2012.04810.xSearch in Google Scholar
22. Shaw-Smith C, Flanagan SE, Patch AM, Grulich-Henn J, Habeb AM, et al. Recessive SLC19A2 mutations are a cause of neonatal diabetes mellitus in thiamine-responsive megaloblastic anaemia. Pediatr Diabetes 2012;13:314–21.10.1111/j.1399-5448.2012.00855.xSearch in Google Scholar
23. Viana MB, Carvalho RI. Thiamine-responsive megaloblastic anemia, sensorineural deafness, and diabetes mellitus: A new syndrome? J Pediatr 1978;93:235–8.10.1016/S0022-3476(78)80503-4Search in Google Scholar
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