Genetic defects of thiamine transport and metabolism: a review of clinical phenotypes, genetics and functional studies.

08:00 EDT 16th May 2019 | BioPortfolio

Summary of "Genetic defects of thiamine transport and metabolism: a review of clinical phenotypes, genetics and functional studies."

Thiamine is a crucial cofactor involved in the maintenance of carbohydrate metabolism and participates in multiple cellular metabolic processes within the cytosol, mitochondria and peroxisomes. Currently, four genetic defects have been described causing impairment of thiamine transport and metabolism: SLC19A2 dysfunction leads to diabetes mellitus, megaloblastic anaemia and sensory-neural hearing loss, whereas SLC19A3, SLC25A19 and TPK1-related disorders result in recurrent encephalopathy, basal ganglia necrosis, generalized dystonia, severe disability and early death. In order to achieve early diagnosis and treatment, biomarkers play an important role. SLC19A3 patients present a profound decrease of free-thiamine in CSF and fibroblasts. TPK1 patients show decreased concentrations of thiamine pyrophosphate in blood and muscle. Thiamine supplementation has been shown to improve diabetes and anaemia control in Rogers' syndrome patients due to SLC19A2 deficiency. In a significant number of patients with SLC19A3, thiamine improves clinical outcome and survival, and prevents further metabolic crisis. In SLC25A19 and TPK1 defects, thiamine has also led to clinical stabilization in single cases. Moreover, thiamine supplementation leads to normal concentrations of free-thiamine in the CSF of SLC19A3 patients. Herein we present a literature review of the current knowledge of the disease including related clinical phenotypes, treatment approaches, update of pathogenic variants, as well as in vitro and in vivo functional models that provide pathogenic evidence and propose mechanisms for thiamine deficiency in humans. This article is protected by copyright. All rights reserved.


Journal Details

This article was published in the following journal.

Name: Journal of inherited metabolic disease
ISSN: 1573-2665


DeepDyve research library

PubMed Articles [41399 Associated PubMed Articles listed on BioPortfolio]

Inherited proximal tubular disorders and nephrolithiasis.

The proximal tubule is responsible for reclaiming water, phosphates and amino acids from the tubular filtrate. There are genetic defects in both phosphate and amino acid transporters leading to nephro...

Thiamine Substitution in Alcohol Use Disorder: A Narrative Review of Medical Guidelines.

Patients with alcohol use disorder (AUD) frequently suffer from cognitive deficits ranging from mild symptoms to most severe forms. Wernicke encephalopathy (WE), caused by thiamine deficiency, is a po...

Understanding the basis of Ehlers-Danlos syndrome in the era of the next-generation sequencing.

Ehlers-Danlos syndrome (EDS) is a clinically and genetically heterogeneous group of heritable connective tissue disorders (HCTDs) defined by joint laxity, skin alterations, and joint hypermobility. Th...

Thiamine Prescribing and Wernicke's Encephalopathy Risk Factors in Patients With Alcohol Use Disorders at a Psychiatric Hospital.

Alcohol use disorder (AUD) is the leading cause of thiamine deficiency and can lead to Wernicke's encephalopathy (WE). WE has a higher prevalence of development in patients with AUD, and current recom...

An overview of tools for post-analysis of high-throughput sequencing data in clinical study.

With the advance of high-throughout sequencing technology and its extensive application in clinical diagnosis, analysis of sequencing data has become an important part of clinical diagnosis. To date, ...

Clinical Trials [8175 Associated Clinical Trials listed on BioPortfolio]

Thiamine Supplement in Patients With Severe Hyperthyroidism

Thyrotoxicosis is a hypermetabolic state in which there is increased utilization of thiamine. Thiamine deficiency has been observed in association with hyperthyroidism. Several studies doc...

The Effect of SLC19A3 Inhibition on the Pharmacokinetics of Thiamine

Subjects will be administered thiamine, thiamine with metformin, and thiamine with trimethoprim to determine whether taking a drug and a vitamin together affects the body's ability to abso...

Thiamine Supplementation in Heart Failure

Heart failure (HF) is a major cardiovascular disease with increasing prevalence. Thiamine deficiency is common in HF patients. Previous small studies have shown that thiamine supplementati...

Thiamine Responsive Disorders (TRD) Among Infants in Lao PDR

A hospital- and community-based study in Vientiane, Lao PDR, which will include a group of hospitalized children 21 days to

Thiamine vs. Placebo to Increase Oxygen Consumption After Cardiac Arrest

This study is to evaluate whether thiamine can increase oxygen consumption and lower lactate in patients who initially survive an in-hospital cardiac arrest. Patients who are successfully ...

Medical and Biotech [MESH] Definitions

Veterinary coccidiostat that interferes with thiamine metabolism. It may cause thiamine deficiency.

The use of the GENETIC VARIATION of known functions or phenotypes to correlate the causal effects of those functions or phenotypes with a disease outcome.

The discipline studying genetic composition of populations and effects of factors such as GENETIC SELECTION, population size, MUTATION, migration, and GENETIC DRIFT on the frequencies of various GENOTYPES and PHENOTYPES using a variety of GENETIC TECHNIQUES.

Autosomal recessive neurodegenerative disorders caused by lysosomal membrane transport defects that result in accumulation of free sialic acid (N-ACETYLNEURAMINIC ACID) within the lysosomes. The two main clinical phenotypes, which are allelic variants of the SLC17A5 gene, are ISSD, a severe infantile form, or Salla disease, a slowly progressive adult form, named for the geographic area in Finland where the kindred first studied resided.

Formal programs for assessing drug prescription against some standard. Drug utilization review may consider clinical appropriateness, cost effectiveness, and, in some cases, outcomes. Review is usually retrospective, but some analysis may be done before drugs are dispensed (as in computer systems which advise physicians when prescriptions are entered). Drug utilization review is mandated for Medicaid programs beginning in 1993.

Quick Search


DeepDyve research library

Relevant Topics

Diabetes is a lifelong condition that causes a person's blood sugar level to become too high. The two main types of diabetes are: type 1 diabetes type 2 diabetes In the UK, diabetes affects approximately 2.9 million people. There are a...

Hearing, auditory perception, or audition is the ability to perceive sound by detecting vibrations, changes in the pressure of the surrounding medium through time, through an organ such as the ear. Sound may be heard through solid, liquid, or gaseous mat...

Arthritis Fibromyalgia Gout Lupus Rheumatic Rheumatology is the medical specialty concerned with the diagnosis and management of disease involving joints, tendons, muscles, ligaments and associated structures (Oxford Medical Diction...

Searches Linking to this Article