Case Report: Genetic and Clinical Features of Maternal Uniparental Isodisomy-Induced Thiamine-Responsive Megaloblastic Anemia Syndrome

Abstract

Background: Thiamine-responsive megaloblastic anemia syndrome (TRMA) is a rare autosomal recessive hereditary disease due to mutations in SLC19A2. Some cases show familial inheritance.Case report: A female patient (from a gravida 1, para 1 mother) of 3.5 years of age was admitted to the Pediatric Hematology Department of Xianyang Caihong Hospital in June 2019. The patient had severe anemia, acupoint-size bleeding spots, and a few ecchymoses all over her body, as well as astigmatism and hyperopia. Hearing was normal. The patient had diabetes. Bone marrow biopsy suggested a myelodysplastic syndrome. The patient had a c.515G>A (p.G172D) homozygous mutation of SLC19A2 (NM_006996), indicating TRMA. Genetic testing revealed that the two alleles were inherited from her mother alone due to maternal uniparental isodisomy (UPD). The patient was treated with thiamine and a subcutaneous injection of insulin. The patient recovered well and was discharged. She continued thiamine and insulin at the same dose and was followed once a month. The last follow-up on September 15, 2020, showed no anemia or bleeding. She had a sound hearing and normal blood routine and fasting glucose levels. Hyperopia and astigmatism did not improve.Conclusion: The patient had TRMA induced by the c.515G>A (p.G172D) homozygous mutation of SLC19A2 inherited through maternal UPD. The genetic diagnosis of TRMA is of significance for guiding clinical treatment. Early treatment with exogenous thiamine can improve some of the clinical features of TRMA.

Leber congenital amaurosis as an initial manifestation in a Chinese patient with thiamine‐responsive megaloblastic anemia syndrome

“…But we do not know if they will show up later. The similar situation, delayed diagnosis, has been reported in many previous cases (Kang et al, 2021; Odaman‐Al et al, 2019; Pichler et al, 2012; Pomahačová et al, 2017; Potter et al, 2017). This is mostly attributed to the low awareness of clinicians for this syndrome and treating TRMA as separate unrelated diseases over a long period of time.…”

Systematic Review of Treatment of Beta-Cell Monogenic Diabetes

“…The data from case reports and case series are shown in tables 7 and 8, respectively. Diabetes was diagnosed at the median age of 1.15 (range, 0.2 – 5.4, n=44) years in case reports 88–116 and between median ages of 1.4 and 2.2 (0.1 – 12, n=51) years in the three case series 117–119 . Insulin was the most common therapy for diabetes (n=89/95) with one patient also using SU (glimepiride), and 6 not receiving any antidiabetic therapy.…”

Acute hearing and visual loss caused by thiamine deficiency

“…Thiamine transporter gene defects lead to dysfunction of multiple cellular metabolic processes. TRMA is characterized by megaloblastic anaemia, diabetes, and sensory-neural deafness and is also associated with congenital heart disease, arrhythmia, cardiomyopathy, retinal degeneration, optic atrophy, and stroke [ 8 , 9 ].…”