Search

Thiamine-responsive megaloblastic anaemia (TRMA) is a rare autosomal recessive disorder characterised by the clinical triad of megaloblastic anaemia, sensorineural hearing loss and diabetes mellitus (DM) in young patients. We present a case of a young man with type 1 DM who presented with pancytopenia of unclear aetiology, initially attributed to a COVID-19 infection. After obtaining a bone marrow biopsy and pursuing genetic testing, two pathogenic variants of the SLC19A2 gene consistent with TRMA were discovered in this patient. Treatment with 100 mg of thiamine oral supplementation daily led to the complete resolution of his pancytopenia. It is important to consider a genetic cause of pancytopenia in a young person. Early recognition and diagnosis of TRMA can be life-altering given early treatment can reduce insulin requirements and resolve anaemia., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

A female child with deafness was diagnosed to have neonatal diabetes mellitus at the age of 6 months, on routine evaluation prior to cochlear implant surgery. She presented to us at 11 months of age with diabetic ketoacidosis due to an intercurrent febrile illness. Her haematological parameters showed megaloblastic anaemia and thrombocytopenia. Therefore a possibility of Thiamine Responsive Megaloblastic Anaemia (TRMA) syndrome was considered. She was empirically treated with parenteral thiamine hydrochloride (Hcl). Subsequently, due to the unavailability of pharmacological preparation of oral thiamine Hcl in a recommended dose she was treated with benfotiamine. She had a sustained improvement in all her haematological parameters on oral benfotiamine. The insulin requirement progressively reduced and she is currently in remission for last 2 years. The genetic analysis confirmed the diagnosis of TRMA syndrome. Thus benfotiamine can be considered a new treatment option in management of TRMA syndrome., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Thiamine-responsive megaloblastic anaemia (TRMA) is a syndrome associated with megaloblastic anaemia, diabetes mellitus and sensorineural deafness, due to mutations in the SLC19A2 gene, which codes for a thiamine carrier protein. Oral thiamine supplementation is the main treatment. We report the case of a 25-year-old woman known for TRMA, who presented with pancytopenia (haemoglobin 7.6 g/dL, leucocytes 2.9×10 9 /L, thrombocytes 6×10 9 /L) revealed by dyspnoea. Investigations excluded coagulopathy, a recent viral infection, vitamin and iron deficiencies, and a malignant process. We later found out that thiamine treatment had been discontinued 5 weeks before, due to prescription error. Parenteral thiamine administration resulted in the recovery of haematopoiesis within 3 weeks. Pancytopenia is uncommon in patients with TRMA. Pre-existing medullary impairment caused by the patient's daily antipsychotic medications or the natural course of the syndrome may explain the severity of the laboratory findings in our patient., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

This report describes a 26 year old woman, of Pakistani origin, who presented five months postpartum with severe megaloblastic anaemia as a result of nutritional folate deficiency. This case was unusual in that a small number of myeloblasts were present in the peripheral blood at presentation, and this circulating population temporarily increased in size when folate replacement was begun. We also highlight the need to recognise the non-linear relation between haematocrit and red blood cell folate concentration when the haematocrit is very low (< 0.15) and emphasise the importance of the clinical history.

Aims: To determine the maturity of reticulocytes in patients with anaemia as a result of various haematological disorders including those with qualitative abnormalities such as ineffective erythropoiesis or dyserythropoiesis., Methods: The number of mature reticulocytes was measured with flow cytometry in venous blood samples from 122 patients with haematological disorders and 100 healthy controls. Reticulocytes were classified into three categories by the fluorescence intensity of auramin O staining: low fluorescence ratio (LFR), medium fluorescence ratio (MFR), and high fluorescence ratio (HFR). Immature reticulocytes were determined as the aggregate of MFR and HFR (%)., Results: The mean (2SD) number of immature reticulocytes in 100 normal subjects was 9.0 (7.0)%. Significantly high mean values of immature reticulocytes with a normal or reduced reticulocyte count were shown in 90 patients with dyserythropoietic or ineffective erythropoietic conditions, such as acute myeloid leukaemia (AML) (n = 37), myelodysplastic syndrome (MDS) (n = 35), aplastic anaemia (AA) (n = 8), or megaloblastic anaemia (MA), (n = 6). Reticulocyte ratios returned to normal after successful treatment of patients with AML (n = 10) and MA (n = 3). However, high percentages of immature reticulocytes with increased reticulocyte counts were consistently observed in patients with enhanced erythropoiesis such as those with acquired autoimmune haemolytic anaemias (AIHA) (n = 4) or acute blood loss (ABL) (n = 4). Reticulocyte maturity was within the normal range in patients with reduced erythropoiesis such as occurs in chronic renal failure (CRF) (n = 11), or in iron deficiency anaemia (IDA) (n = 13)., Conclusions: The evaluation of reticulocyte maturity with total reticulocyte count seems to be clinically useful for estimating the qualitative impairment of erythropoiesis, and so could help differentiate haematological disorders.

Methylation of cytosine residues in DNA samples, collected before and serially after cobalamin treatment from patients with cobalamin deficiency, was studied using restriction endonucleases Hpa II and Msp I and an epsilon globin gene probe. There was no evidence of hypomethylation in any of the samples. It was concluded that although hypomethylation of metabolites such as choline occurs, that of DNA is preserved in megaloblastic anaemia.

Lymphocyte subpopulations and intrinsic factor and gastric parietal cell antibodies have been measured in 23 patients with megaloblastic anaemia who responded to treatment with hydroxocobalamin. The ratio of helper (OKT4) to suppressor (OKT8) lymphocytes was significantly increased in patients with intrinsic factor antibody compared with those who lacked the antibody. No such correlation was found for gastric parietal cell antibody. Alterations in the lymphocyte helper to suppressor (OKT4:OKT8) ratio may be associated with pernicious anaemia.