Pediatric Diabetes 2007: 8: 239–241 All rights reserved # 2007 The Authors Journal compilation # 2007 Blackwell Munksgaard Pediatric Diabetes Case Report Thiamine-responsive megaloblastic anaemia: a cause of syndromic diabetes in childhood Olsen BS, Hahnemann JMD, Schwartz M, Østergaard E. Thiamine- responsive megaloblastic anaemia: a cause of syndromic diabetes in childhood. Pediatric Diabetes 2007: 8: 239–241. Abstract: Thiamine-responsive megaloblastic anaemia (TRMA) is a rare autosomal recessive condition, characterized by megaloblastic anaemia, non-autoimmune diabetes mellitus, and sensorineural hearing loss. We describe three infants with TRMA from two consanguineous Pakistani families, who were not known to be related but originated from the same area in Pakistan. All children were homozygous, and the parents were heterozygous for a c.196G.T mutation in the SLC19A2 gene on chromosome 1q23.3, which encodes a high-affinity thiamine transporter. The result is an abnormal thiamine transportation and vitamin deficiency in the cells. Thiamine in high doses (100–200 mg/d) reversed the anaemia in all our patients. Two patients discontinued insulin treatment successfully after a short period, while the third patient had to continue with insulin. The hearing loss persisted in all three children. The diagnosis of TRMA should be suspected in patients with syndromic diabetes including hearing loss and anaemia, even if the latter is only very mild and, particularly, in the case of consanguinity. Birthe S Olsen a , Johanne MD Hahnemann b , Marianne Schwartz c and Elsebeth Østergaard b,c a Department of Paediatrics, Glostrup University Hospital, Glostrup, Denmark; b The Kennedy Institute – National Eye Clinic, Glostrup, Denmark; and c Department of Clinical Genetics, Rigshospitalet, Copenhagen, Denmark Key words: autosomal recessive – deafness – megaloblastic anaemia – non-immune diabetes – SLC19A2 gene – TRMA Corresponding author: Birthe Susanne Olsen Department of Paediatrics Glostrup University Hospital DK-2600 Glostrup Denmark. Tel: 14543233021; fax: 14543233964; e-mail: bsuo@glostruphosp.kbhamt.dk Submitted 27 January 2006. Accepted for publication 15 January 2007 In Denmark, the majority of children (.90%) with diabetes have type 1 diabetes (1). Thiamine-responsive megaloblastic anaemia (TRMA) or Rogers syndrome is a rare autosomal recessive condition, first described by Rogers et al. in 1969 (2) and till now reported in less than 30 families (3). The cardinal features of TRMA are non-autoimmune diabetes mellitus, meg- aloblastic anaemia, and sensorineural hearing loss (2). Less frequently occurring symptoms are cardiac anomalies (4, 5), optic atrophy, retinal degeneration (6, 7), and cerebrovascular accidents (8). In 1999, a mutation in the SLC19A2 gene on chromosome 1q23.3 was first reported as the cause of the disorder (9–11). The gene encodes a high-affinity thiamine transporter, and mutations in the gene lead to abnormal thiamine transport and vitamin defi- ciency in the cells. We present here three patients, all diagnosed with TRMA at an young age in our Danish paediatric diabetes clinic. All patients had a Pakistani back- ground, and two of the patients were cousins, while the third was apparently unrelated to the others. All three patients, however, came from a rather limited area in Pakistan. Case reports Case 1 was a boy and the first child of healthy first- cousin parents. Non-immune diabetes and megalo- blastic anaemia was diagnosed at 10 months and severe sensory–neural hearing loss at 2 yr. At age 4 yr, TRMA was suspected and diagnosed by mutation analysis. The boy started oral treatment with thiamine 200 mg/24 h (Table 1). 239