Importance of Immediate Thiamine Therapy in Children with Suspected Thiamine-Responsive Megaloblastic Anemia—Report on Two Patients Carrying a Novel SLC19A2 Gene Mutation

Milenković, Dragan; Franco, Elisa De; Bilić, Ernest; Putarek, Nataša Rojnić; Krnić, Nevena

doi:10.1055/s-0040-1717136

Cited by 4 publications

(8 citation statements)

References 11 publications

(30 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Apart from typical symptoms, stroke or stroke-like episodes could also be observed, even with homozygous null mutations. Basic therapy is pharmacological doses of thiamine (25–75 mg per day) [ 81 , 82 , 86 , 87 , 88 , 89 ]. However pathogenesis of stroke-like episodes and other neurological features in patients with TRMA is still unclear; it may be connected with complex I of respiratory chain dysfunction due to thiamine deficiency, induction of oxidative stress and reduction in oxidative phosphorylation due to the lower synthesis of thiamine pyrophosphate, which is the cofactor of PDHE1α [ 81 , 82 , 88 , 90 ].…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Stroke-like Episodes in Inherited Neurometabolic Disorders

2022

View full text Add to dashboard Cite

Stroke-like episodes (SLEs) are significant clinical manifestations of metabolic disorders affecting the central nervous system. Morphological equivalents presented in neuroimaging procedures are described as stroke-like lesions (SLLs). It is crucial to distinguish SLEs from cerebral infarction or intracerebral hemorrhage, mainly due to the variety in management. Another significant issue to underline is the meaning of the main pathogenetic hypotheses in the development of SLEs. The diagnostic process is based on the patient’s medical history, physical and neurological examination, neuroimaging techniques and laboratory and genetic testing. Implementation of treatment is generally symptomatic and includes L-arginine supplementation and adequate antiepileptic management. The main aim of the current review was to summarize the basic and actual knowledge about the occurrence of SLEs in various inherited neurometabolic disorders, discuss the possible pathomechanism of their development, underline the role of neuroimaging in the detection of SLLs and identification of the electroencephalographic patterns as well as histological abnormalities in inherited disorders of metabolism.

show abstract

Section: Resultsmentioning

confidence: 99%

“…Neurological manifestations are observed in 20–40 % of patients with TRMA in their early childhood [ 81 , 82 , 87 , 88 ]. THTR2 transporter seems to be more essential for thiamine brain active transport than the THTR1 channel [ 88 , 90 ] ( Table 4 ) [ 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 ].…”

Section: Resultsmentioning

confidence: 99%

Stroke-like Episodes in Inherited Neurometabolic Disorders

2022

View full text Add to dashboard Cite

show abstract

“…About 40 SLC19A2 mutations have been characterized, among which most are missense, nonsense, or insertions and deletions. 2 Such mutations have been described to lead to abnormal production of either aberrant or absent thiamine transporter protein, causing phenotype variations, and have been linked to TRMA presenting as a spectrum of symptoms and associated conditions. Other mutations may cause protein misfolding, interrupting its integration with the cell membrane.…”

Section: Discussionmentioning

confidence: 99%

“…The hemoglobin level in one patient increased to 12.9 g/dL, but insulin therapy was still required. 2,9 Even with a high thiamine therapy dose, hearing loss may be progressive, irreversible, or unresponsive, and it is worth noting that cochlear implantation may be beneficial for improving hearing loss, with significant benefits. 10 Although it is simple, early thiamine therapy, when suspecting TRMA, may suffice to improve anemia and aid euglycemic control.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Thiamine-Responsive Megaloblastic Anemia Syndrome Combined with Thalassemia Trait: A Rare Association

Mabrouk,

Aburawi

2023

Ibnosina Journal of Medicine and Biomedical Sciences

View full text Add to dashboard Cite

Introduction Thiamine-responsive megaloblastic anemia syndrome (TRMA, OMIM reference 249270), also known as Rogers' syndrome, is a rare type of anemia characterized by the triad megaloblastic anemia, sensorineural hearing loss, and diabetes mellitus (DM). Disturbance of thiamine transport into cells results from homozygous or compound heterozygous mutations in the SLC19A2 gene. Case Report We report the case of an 8-year-old girl who presented at age 4 years with anemia. She had a combined hematological profile of microcytic and macrocytic anemia. The parents refused bone marrow aspiration and genetic diagnosis. Hemoglobin electrophoresis established the thalassemia trait. She was later confirmed to have sensorineural deafness and monogenic DM. A tentative TRMA diagnosis was based on megaloblastic anemia, sensorineural deafness, and monogenic DM triad. The patient was treated empirically with a daily dose of thiamine 200 mg; her hemoglobin level normalized, but the deafness and DM did not improve. Conclusion In routine practice, patients with TRMA must be evaluated thoroughly for other causes of megaloblastic anemia, including therapeutic thiamine trials in the presence of sensorineural deafness or DM. These patients should be followed throughout their life span both for DM and to control their response to thiamine therapy for megaloblastic anemia.

show abstract

Systematic Review of Treatment of Beta-Cell Monogenic Diabetes

Naylor

Patel

Kettunen

et al. 2023

Preprint

View full text Add to dashboard Cite

Background: Beta-cell monogenic forms of diabetes are the area of diabetes care with the strongest support for a precision medicine approach. We systematically reviewed treatment of hyperglycemia in GCK-related hyperglycemia, HNF1A-diabetes, HNF4A-diabetes, HNF1B-diabetes, Mitochondrial diabetes (MD) due to m.3243A>G variant, 6q24-transient neonatal diabetes (TND) and SLC19A2-diabetes (Thiamine-Responsive Megaloblastic Anemia, TRMA). Methods: Systematic review with data sources from PubMed, MEDLINE and Embase were performed answering specific therapeutic questions for the different subtypes. Individual and group level data was extracted for glycemic outcomes in individuals with genetically confirmed monogenic diabetes. Results: 147 studies met inclusion criteria with only six experimental studies (four randomized trials for HNF1A-diabetes) and the rest being single case reports or cohort studies. Most studies were rated as having moderate or serious risk of bias. For GCK-related hyperglycemia, six studies (35 individuals) showed no deterioration in HbA1c on discontinuing glucose lowering therapy. A randomized trial (n=18 per group) showed that sulfonylureas (SU) were more effective in HNF1A-diabetes than in type 2 diabetes, and cohort and case studies supported SU effectiveness in lowering HbA1c. Two crossover trials (n=15 and n=16) suggested glinides and GLP-1 receptor agonists might be used in place of SU. Evidence for HNF4A-diabetes was limited to three studies (16 individuals) showing lower HbA1c with SU therapy. The 13 studies in HNF1B-diabetes (n=301) and 10 in MD with m.3243A>G variant (n=250) showed that while some patients can be treated with oral agents the majority of patients were insulin treated. In HNF1B-diabetes the attempts to transfer from insulin to oral hypoglycemic agents (OHA) were unsuccessful in most cases. In 6q24-TND there were insufficient studies supporting OHA close to diagnosis before remission but more support for their use after relapse. In SLC19A2-diabetes there was some evidence that treatment with thiamine improved glycemic control and reduced insulin requirement while less than half achieved insulin-independency. Conclusion: There is limited evidence to guide the treatment in monogenic diabetes with most studies being non-randomized and small. The combined data does support: no treatment being needed in GCK-related hyperglycemia; SU being used as the first line treatment in HNF1A-diabetes; SU can be tried in HNF4A-diabetes; insulin often needed in HNF1B-diabetes and MD with the m.3243A>G variant; SU can be tried in 6q24-TND relapse; and thiamine may improve glycemic control in SLC19A2-diabetes. Further evidence, particularly randomized comparative studies, are needed to examine the optimum treatment for glycemic response in all monogenic subtypes.

show abstract

Importance of Immediate Thiamine Therapy in Children with Suspected Thiamine-Responsive Megaloblastic Anemia—Report on Two Patients Carrying a Novel SLC19A2 Gene Mutation

Cited by 4 publications

References 11 publications

Stroke-like Episodes in Inherited Neurometabolic Disorders

Stroke-like Episodes in Inherited Neurometabolic Disorders

Thiamine-Responsive Megaloblastic Anemia Syndrome Combined with Thalassemia Trait: A Rare Association

Systematic Review of Treatment of Beta-Cell Monogenic Diabetes

Contact Info

Product

Resources

About