Pediatrics

Symptoms & The Classic Triad

At a Glance

TRMA’s classic pattern includes anemia caused by unusually large red blood cells, non-autoimmune diabetes, and hearing loss that is often permanent. Symptoms may appear at different ages, so a child can have TRMA when only one is present; eye or heart problems are possible but variable.

Thiamine-Responsive Megaloblastic Anemia (TRMA) is often described by doctors as a “triad”—a group of three core symptoms that occur together ^[1]. However, for many families, these symptoms do not arrive all at once. They can appear at different times, sometimes years apart, and may develop anytime from birth through adolescence ^[2]^[3].

The Classic Triad

The “classic” presentation of TRMA involves three specific conditions:

Megaloblastic Anemia: This is a type of anemia where the bone marrow produces red blood cells that are unusually large (megaloblastic) and do not function correctly ^[4]. Unlike more common forms of anemia, this is not caused by a lack of iron, Vitamin B12, or folate in the diet; rather, it is caused by the body’s inability to get thiamine into the blood-producing cells ^[5]^[6].
Diabetes Mellitus: In TRMA, diabetes is non-autoimmune, meaning the body’s immune system is not attacking the pancreas. Instead, the cells that produce insulin struggle to function without enough thiamine ^[7]. This often develops in infancy or early childhood (one registry study noted a median age of onset around 10 to 17 months, though it can occur earlier or later) ^[2]^[8].
Sensorineural Hearing Loss: This is hearing loss caused by damage to the tiny hair cells in the inner ear or the pathways that carry sound signals to the brain ^[3]. It is typically permanent and often affects both ears ^[9].

Atypical and Early Presentations

It is important to know that the absence of one or two of these symptoms does not rule out TRMA ^[9]. Because the symptoms can emerge at different stages, your child might only show one sign at the time of diagnosis ^[10].

Diabetes First: Some children present with high blood sugar (diabetes) as their only symptom for months or years before anemia or hearing loss is detected ^[2].
Hearing Loss First: In other cases, severe hearing loss is the first sign noticed by parents, occurring before any changes in blood counts or blood sugar ^[3].
Incomplete Triad: Some patients may never develop the full triad, or the use of thiamine treatment early in life may prevent some symptoms—like anemia—from ever appearing ^[11]^[12].

Beyond the Triad: Additional Symptoms

While the triad is the most common way TRMA is recognized, the lack of thiamine can affect other parts of the body as well. These extra-triad manifestations are less common and highly variable, so they should be viewed as reported possibilities rather than inevitable outcomes.

Vision and Eye Health

The eyes are very sensitive to thiamine levels. Some individuals with TRMA develop ophthalmologic (eye-related) conditions, including:

Retinal Dystrophy/Retinitis Pigmentosa: A breakdown of the light-sensitive tissue at the back of the eye, which can cause trouble seeing at night or loss of side vision ^[13]^[14].
Optic Atrophy: Damage to the nerve that connects the eye to the brain ^[15].
Cone-Rod Dystrophy: A condition affecting the cells in the eye responsible for color and detail ^[16].

Heart and Rhythm

TRMA can sometimes affect the heart’s electrical system, leading to cardiac arrhythmias (irregular heartbeats) ^[17]. This can include supraventricular tachycardia (an abnormally fast heartbeat) or the absence of certain waves on an electrocardiogram (ECG), which tracks the heart’s electrical activity ^[18]^[19].

Other Observations

Rarely, other symptoms have been reported in case studies, such as shorter than average height (short stature), an enlarged liver (hepatomegaly), or neurological issues like seizures or strokes ^[17]^[20]^[21]. Because every child is different, your care team will tailor an individualized surveillance plan to monitor for these possibilities.

Common questions in this guide

What are the three classic symptoms of TRMA?

The classic TRMA triad consists of megaloblastic anemia, non-autoimmune diabetes mellitus, and sensorineural hearing loss. The three problems do not always begin at the same age or appear together.

Can a child have TRMA without all three parts of the triad?

Yes. One or two features may be missing when TRMA is recognized, and some people never develop the full triad. Starting thiamine treatment early may prevent some features, including anemia, from appearing.

Which symptom may be the first sign of TRMA?

There is no single pattern. Some children first develop high blood sugar or diabetes, while others first show severe hearing loss; blood-count changes may be found later.

What symptoms can occur beyond the classic TRMA triad?

Possible additional findings include eye problems such as retinal dystrophy, optic nerve damage, or cone-rod dystrophy, as well as irregular heart rhythms. Rare reports also describe short stature, an enlarged liver, seizures, or strokes, but these findings are variable and are not expected in every person.

What does non-autoimmune diabetes mean in TRMA?

It means the immune system is not attacking the insulin-producing cells in the pancreas. In TRMA, these cells may have difficulty functioning when thiamine is not adequately available.

What health monitoring may a child with TRMA need?

The monitoring plan is individualized and may include blood counts, blood sugar, hearing, vision, and heart-rhythm checks. Ask the care team when the next hearing test, eye exam, blood test, or electrocardiogram (ECG) is needed and which changes should prompt a call.

Get notified when new evidence is published on Thiamine-responsive megaloblastic anemia syndrome.

We monitor PubMed for new peer-reviewed studies on this topic and email a short summary when something meaningful changes.

References (21)

1
[Thiamine-responsive megaloblastic anemia or Rogers syndrome: A literature review].
Lu H, Lu H, Vaucher J, et al.
La Revue de medecine interne 2019; (40(1)):20-27 doi:10.1016/j.revmed.2018.06.005.
PMID: 30031565
2
Pharmacogenomics in diabetes: outcomes of thiamine therapy in TRMA syndrome.
Habeb AM, Flanagan SE, Zulali MA, et al.
Diabetologia 2018; (61(5)):1027-1036 doi:10.1007/s00125-018-4554-x.
PMID: 29450569
3
Thiamine responsive megaloblastic anemia syndrome: a novel homozygous SLC19A2 gene mutation identified.
Mikstiene V, Songailiene J, Byckova J, et al.
American journal of medical genetics. Part A 2015; (167(7)):1605-9 doi:10.1002/ajmg.a.37015.
PMID: 25707023
4
Thiamine-Responsive Megaloblastic Anemia Syndrome Mimicking Myelodysplastic Neoplasm.
Klötzer C, Schnabel F, Kubasch AS, et al.
Acta haematologica 2025; (148(4)):380-385 doi:10.1159/000542286.
PMID: 39467528
5
Thiamine Responsive Megaloblastic Anaemia, Diabetes Mellitus and Sensorineural Hearing Loss in a Child.
Khurshid A, Fatimah S, Altaf C, et al.
Journal of the College of Physicians and Surgeons--Pakistan : JCPSP 2018; (28(9)):S169-S171 doi:10.29271/jcpsp.2018.09.S169.
PMID: 30173687
6
Infantile-onset thiamine responsive megaloblastic anemia syndrome with SLC19A2 mutation: a case report.
Katipoğlu N, Karapinar TH, Demir K, et al.
Archivos argentinos de pediatria 2017; (115(3)):e153-e156 doi:10.5546/aap.2017.eng.e153.
PMID: 28504500
7
Identification of novel compound heterozygous variants in SLC19A2 and the genotype-phenotype associations in thiamine-responsive megaloblastic anemia.
Zhang S, Qiao Y, Wang Z, et al.
Clinica chimica acta; international journal of clinical chemistry 2021; (516()):157-168 doi:10.1016/j.cca.2021.01.025.
PMID: 33571483
8
Thiamine-Responsive Megaloblastic Anemia-Related Diabetes: Long-Term Clinical Outcomes in 23 Pediatric Patients From the DPV and SWEET Registries.
Warncke K, Prinz N, Iotova V, et al.
Canadian journal of diabetes 2021; (45(6)):539-545 doi:10.1016/j.jcjd.2020.11.006.
PMID: 33388275
9
Diagnosis of a patient with severe sensorineural hearing loss as the initial symptom caused by novel compound heterozygous variant in SLC19A2 gene.
Shi Y, Li J, Chen X, et al.
Brazilian journal of otorhinolaryngology 2025; (91(4)):101581 doi:10.1016/j.bjorl.2025.101581.
PMID: 40220483
10
An Endemic Region of Thiamine-Responsive Megaloblastic Anemia Caused by an SLC19A2 c.1223+1G>A Founder Mutation.
Gurzhikhanova M, Fomenko S, Chekanov N, et al.
International journal of molecular sciences 2026; (27(14)) doi:10.3390/ijms27146274.
PMID: 42511616
11
Beta cell function and clinical course in three siblings with thiamine-responsive megaloblastic anemia (TRMA) treated with thiamine supplementation.
Potter K, Wu J, Lauzon J, Ho J
Journal of pediatric endocrinology & metabolism : JPEM 2017; (30(2)):241-246.
PMID: 28076318
12
Early thiamine therapy in Rogers syndrome: Systematic review of hematologic, auditory and glycemic outcomes.
Upadhyay Z, Sudani S, Jain A
Bioinformation 2026; (22(1)):26-30 doi:10.6026/973206300220026.
PMID: 41960466
13
Leber congenital amaurosis as an initial manifestation in a Chinese patient with thiamine-responsive megaloblastic anemia syndrome.
Wu S, Yuan Z, Sun Z, et al.
American journal of medical genetics. Part A 2022; (188(3)):948-952 doi:10.1002/ajmg.a.62582.
PMID: 34821467
14
Novel nonsense mutation (p.Ile411Metfs*12) in the SLC19A2 gene causing Thiamine Responsive Megaloblastic Anemia in an Indian patient.
Manimaran P, Subramanian VS, Karthi S, et al.
Clinica chimica acta; international journal of clinical chemistry 2016; (452()):44-9.
PMID: 26549656
15
Thiamine-Responsive Megaloblastic Anaemia With Hypothyroidism, A Puzzling Association.
Rai VR, Ibrahim MN, Javed MN, et al.
Journal of Ayub Medical College, Abbottabad : JAMC 2023; (35(Suppl 1)(4)):S804-S806 doi:10.55519/JAMC-S4-12486.
PMID: 38406914
16
LONG-TERM MULTIMODAL IMAGING OF OCULAR FINDINGS ASSOCIATED WITH THIAMINE-RESPONSIVE MEGALOBLASTIC ANEMIA.
Tsui E, Tauber J, Barbazetto I, Gelman SK
Retinal cases & brief reports 2020; (14(3)):247-250 doi:10.1097/ICB.0000000000000686.
PMID: 29210962
17
TRMA syndrome with a severe phenotype, cerebral infarction, and novel compound heterozygous SLC19A2 mutation: a case report.
Li X, Cheng Q, Ding Y, et al.
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18
Arrhythmia in thiamine responsive megaloblastic anemia syndrome.
Argun M, Baykan A, Hatipoğlu N, et al.
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PMID: 30511554
19
An extremely rare case of Rogers syndrome or thiamine responsive megaloblastic anemia.
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20
Recurrent Stroke in a Child with TRMA Syndrome and SLC19A2 Gene Mutation.
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PMID: 29379566
21
Thiamine-responsive megaloblastic anemia syndrome with novel compound heterozygous SLC19A2 mutations and thrombotic events: a case report.
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This page describes TRMA symptoms for educational purposes only and does not constitute medical advice. Your child's healthcare team should interpret symptoms and plan blood, hearing, eye, and other monitoring.