Mikstiene Violeta, Songailiene Jurgita, Byckova Jekaterina, Rutkauskiene Giedre, Jasinskiene Edita, Verkauskiene Rasa, Lesinskas Eugenijus, Utkus Algirdas
Department of Human and Medical Genetics, Faculty of Medicine, Vilnius University, Vilnius, Lithuania.
Centre of Ear, Nose and Throat Diseases, Vilnius University Hospital Santariškių Clinics, Vilnius, Lithuania.
Am J Med Genet A. 2015 Jul;167(7):1605-9. doi: 10.1002/ajmg.a.37015. Epub 2015 Feb 23.
Thiamine responsive megaloblastic anemia syndrome (TRMAS) is a rare autosomal recessive disorder especially in countries where consanguinity is uncommon. Three main features are characteristic of the disease - megaloblastic anemia, early onset deafness, and non-type I diabetes. TRMAS is a Mendelian disorder; a gene SLC19A2 coding high affinity thiamine transporter mediating vitamin B1 uptake through cell membrane has been identified. We present the first patient with TRMAS in Lithuania - a 3-year-old boy born to a non-consanguineous family with a novel homozygous SLC19A2 gene mutation. The patient had insulin dependent diabetes (onset 11 months), respiratory illness (onset 11 months), bilateral profound hearing loss (onset at 7 months, verified at 20 months), refractory anemia (onset 2 years), and decreased vision acuity and photophobia (onset 2.5 years). The psychomotor abilities developed according to age. Phenotypic evaluation did not reveal any dysmorphic features. The clinical diagnosis of TRMAS was suspected and daily supplementation with thiamine 100 mg was started. The condition of the patient markedly improved several days after the initiation of treatment. The results of SLC19A2 gene molecular testing confirmed the clinical diagnosis - novel homozygous c.[205G>T], p.[(Val69Phe)] mutation changing conserved amino acid residue or even interfering the mRNA splicing. Clinical heterogeneity, diverse dynamics, and wide spectrum of symptoms are aggravating factors in the diagnosis. The possibility of treatment demands early recognition of disorder to facilitate the improvement of the patient's condition.
硫胺素反应性巨幼细胞贫血综合征(TRMAS)是一种罕见的常染色体隐性疾病,在近亲结婚不常见的国家尤为如此。该疾病具有三个主要特征——巨幼细胞贫血、早发性耳聋和非I型糖尿病。TRMAS是一种孟德尔疾病;已鉴定出一个编码高亲和力硫胺素转运蛋白的基因SLC19A2,该转运蛋白介导维生素B1通过细胞膜的摄取。我们报告了立陶宛首例TRMAS患者——一名3岁男孩,出生于非近亲家庭,携带一种新的纯合SLC19A2基因突变。该患者患有胰岛素依赖型糖尿病(发病于11个月)、呼吸系统疾病(发病于11个月)、双侧重度听力丧失(发病于7个月,20个月时确诊)、难治性贫血(发病于2岁)以及视力下降和畏光(发病于2.5岁)。其精神运动能力随年龄正常发育。表型评估未发现任何畸形特征。怀疑为TRMAS临床诊断,并开始每日补充100毫克硫胺素。治疗开始几天后患者病情明显改善。SLC19A2基因分子检测结果证实了临床诊断——新的纯合c.[205G>T],p.[(Val69Phe)]突变,该突变改变了保守氨基酸残基,甚至干扰了mRNA剪接。临床异质性、多样的动态变化和广泛的症状是诊断中的加重因素。治疗的可能性要求早期识别该疾病,以促进患者病情的改善。