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thiamine-responsive megaloblastic anemia syndrome - Clinical Profile, Genes & Research | Kisho | Kisho

Organ System	Phenotype Count	Example Features
Heart and blood vessels	5	Stroke, Arrhythmia, Ventricular septal defect
Brain and nerves	4	Stroke, Seizure, Ataxia
Blood and immune system	3	Thiamine-responsive megaloblastic anemia, Sideroblastic anemia, Low platelet count (thrombocytopenia)
Eyes	3	Nystagmus, Retinal degeneration, Damage to the optic nerve (optic atrophy)
Growth and development	1	Short stature
Digestive system	1	Gastroesophageal reflux
Hormones	1	Diabetes mellitus
Skin	1	Abnormality of the skin
Ears	1	Inner ear hearing loss (sensorineural hearing impairment)
Muscles	1	Damage to the optic nerve (optic atrophy)

GeneReviews

Clinical Guidance

Thiamine-responsive megaloblastic anemia syndrome (TRMA) is characterized by the triad of megaloblastic anemia, progressive sensorineural hearing loss, and diabetes mellitus. To date, more than 183 individuals from more than 138 families have been identified . Table 2. Thiamine-Responsive Megaloblastic Anemia Syndrome: Frequency of Select Features

Feature	% of Personsw/Feature	Comment
Megaloblastic anemia	60%-70%	Anemia is present in 90% of persons.
Progressive sensorineural deafness	90%	—
Non-type I diabetes mellitus	90%	—
Ophthalmologic manifestations	20%-30%	Incl optic atrophy
Cardiovascular abnormalities	20%-30%	—
Neurologic manifestations	20%-40%	—
Thrombocytopenia	10%-30%	Megaloblastic anemia. The earliest findings of significant bone marrow problems have been in the first year of life and the latest in the teenage years.

Source: GeneReviews — "Thiamine-Responsive Megaloblastic Anemia Syndrome"

Diagnosis

Drawn from GeneReviews diagnostic guidelines, newborn screening panel status (RUSP), and ClinGen gene-disease validity classifications. Reflects current clinical evidence and consensus where available.

GeneReviews

Diagnostic Criteria

Suggestive Findings

Thiamine-responsive megaloblastic anemia syndrome (TRMA) should be suspected in individuals with the following triad of clinical features:

Source: GeneReviews — "Thiamine-Responsive Megaloblastic Anemia Syndrome"

GeneReviews

Differential Diagnosis

Anemia. The combination of megaloblastic red cell changes and ringed sideroblasts in individuals with thiamine-responsive megaloblastic anemia syndrome (TRMA) is unique among anemias influenced by inborn errors of metabolism or nutritional causes. Among acquired anemias, this combination is most suggestive of myelodysplastic syndromes in which megaloblastosis and sideroblasts are often noted. TRMA should not be confused with myelodysplastic disorders of premalignant potential. Progressive sensorineural hearing loss and diabetes mellitus. See . Table 3. Genetic Disorders with Hearing Loss and Diabetes Mellitus in the Differential Diagnosis of Thiamine-Responsive Megaloblastic Anemia Syndrome

Gene / Genetic Mechanism	Disorder	MOI	Overlapping Features	Distinguishing Features / Comment
WFS1	WFS1 Wolfram syndrome spectrum disorder (incl DIDMOAD)	ARAD1	Variable combinations of DM, optic atrophy, deafness	Notably missing megaloblastic anemia thiamine responsiveness
CISD2

Genetic testing for SLC19A2 is available. Testing is considered confirmatory for diagnosis.

Biomarker and diagnostic research for thiamine-responsive megaloblastic anemia syndrome has been reported in the published literature.

Treatment

Compiled from FDA-approved drug records, orphan drug designations, and FDA Adverse Event Reporting System (FAERS) safety data. GeneReviews management guidance is included where available.

No approved treatments are currently available for thiamine-responsive megaloblastic anemia syndrome. The disease remains an area of unmet medical need.

GeneReviews

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with thiamine-responsive megaloblastic anemia syndrome (TRMA), the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 4. Recommended Evaluations Following Initial Diagnosis in Individuals with Thiamine-Responsive Megaloblastic Anemia Syndrome

System/Concern	Evaluation	Comment
Hearing	Audiologic eval	—
Endocrine	Fasting serum glucose concentration, OGTT, urinalysis to diagnose DM	—
Eyes	Ophthalmologic eval	Cardiac
counseling	By genetics professionals1	To inform affected persons families re nature, MOI, implications of TRMA to facilitate medical personal decision making DM = diabetes mellitus; MOI = mode of inheritance; OGTT = oral glucose tolerance test 1.
Treatment of Manifestations in Individuals with Thiamine-Responsive Megaloblastic Anemia Syndrome Manifestation/Concern	Treatment	Considerations/Other Megaloblastic anemia

Source: GeneReviews — "Thiamine-Responsive Megaloblastic Anemia Syndrome"

GeneReviews

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "Thiamine-Responsive Megaloblastic Anemia Syndrome"

Clinical Trials

View trials for thiamine-responsive megaloblastic anemia syndrome

Explore Trials

Research Landscape

Sourced from ClinicalTrials.gov and PubMed. Publication types are classified using NLM-curated article metadata; research type breakdowns reflect the nature of published work for this disease.

No clinical trials have been registered for thiamine-responsive megaloblastic anemia syndrome.

18 publications have been identified in PubMed for thiamine-responsive megaloblastic anemia syndrome. Research spans Case Report / Case Series (47%), Review / Meta-Analysis (29%), and Basic Science / Preclinical (12%).

Research Type	Count	% of Total
Patient case studies	8	47%
Research summaries	5	29%
Laboratory research	2	12%
Testing and diagnosis research	1	6%
Disease patterns and progression	1	6%

Recent Publications

Hariz A (2026). [PMID: 30725939](https://pubmed.ncbi.nlm.nih.gov/30725939/). *Unknown Journal*. [Review / Meta-Analysis]
Upadhyay Z (2026). [PMID: 41960466](https://pubmed.ncbi.nlm.nih.gov/41960466/). *Bioinformation*. [Review / Meta-Analysis]
Jiménez FX (2026). [PMID: 41840683](https://pubmed.ncbi.nlm.nih.gov/41840683/). *Journal of medical case reports*. [Case Report / Case Series]
Dallan A (2025). [PMID: 40186230](https://pubmed.ncbi.nlm.nih.gov/40186230/). *Orphanet journal of rare diseases*. [Review / Meta-Analysis]
Shi Y (2025). [PMID: 40220483](https://pubmed.ncbi.nlm.nih.gov/40220483/). *Brazilian journal of otorhinolaryngology*. [Case Report / Case Series]
Kaur G (2025). [PMID: 38391342](https://pubmed.ncbi.nlm.nih.gov/38391342/). *Indian journal of pathology & microbiology*. [Diagnostic / Biomarker]
Qin Y (2025). [PMID: 40071807](https://pubmed.ncbi.nlm.nih.gov/40071807/). *Endokrynologia Polska*. [Basic Science / Preclinical]
Klötzer C (2025). [PMID: 39467528](https://pubmed.ncbi.nlm.nih.gov/39467528/). *Acta haematologica*. [Case Report / Case Series]
Suanes Zubizarreta CA (2025). [PMID: 41210025](https://pubmed.ncbi.nlm.nih.gov/41210025/). *Cureus*. [Case Report / Case Series]
Shadab M (2025). [PMID: 40377830](https://pubmed.ncbi.nlm.nih.gov/40377830/). *Molecular diagnosis & therapy*. [Case Report / Case Series]

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thiamine-responsive megaloblastic anemia syndrome

Overview

Clinical Presentation

Clinical Guidance

Explore clinical features

Genetic Landscape

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Differential Diagnosis

Treatment

Management Guidelines

Therapies Under Investigation

Clinical Trials

Prognosis

Surveillance Guidelines

Hematologic

Hearing

Endocrine

Cardiac

Neurologic

Research Landscape

Recent Publications

Medical References

External Resources

OMIM

Orphanet

GARD

Questions for Your Care Team

Questions for Your Care Team

thiamine-responsive megaloblastic anemia syndrome

Overview

Clinical Presentation

Clinical Guidance

Explore clinical features

Genetic Landscape

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Differential Diagnosis

Treatment

Management Guidelines

Therapies Under Investigation

Clinical Trials

Prognosis

Surveillance Guidelines

Hematologic

Hearing

Endocrine

Cardiac

Neurologic

Research Landscape

Recent Publications

Medical References

External Resources

OMIM

Orphanet

GARD

Related Diseases

Questions for Your Care Team

Questions for Your Care Team