Also known as: Thiamine metabolism dysfunction syndrome 1 (megaloblastic anemia, diabetes mellitus, and deafness type); THMD1; Megaloblastic anemia, thiamine-responsive, with diabetes mellitus and sensorineural deafness; Rogers syndrome; Thiamine-responsive anemia syndrome
Thiamine-responsive myelodysplasia
OMIM#249270 https://omim.org/entry/249270
1. The Disease:
Thiamine-responsive megaloblastic anemia (TRMA) is characterized by a triad of megaloblastic anemia, non-type I diabetes mellitus, and sensorineural deafness.
2. The symptoms:
TRMA can present at any age between infancy and adolescence, although often not all key features are manifested at onset. TRMA is typically characterized by the triad of megaloblastic anemia responding to thiamine, sensorineural deafness, and non-type I diabetes mellitus. Lack of early signs or symptoms does not exclude the diagnosis.
Clinical megaloblastic anaemia manifestations may comprise hyporexia, lethargy, cephalalgia, pallor, diarrhoea, and paraesthesia in hands and feet.
Other variable clinical signs include retinal dystrophy and optic nerve atrophy; short stature; cardiovascular abnormalities including congenital heart defects such as atrial and/or ventricular septal defect and arrhythmia/conduction anomalies; seizures and strokes.
The variable phenotypic presentation of TRMA syndrome may cause a significant delay between the onset of symptoms and an accurate diagnosis.
3. Actions to take in case of early diagnosis:
A bone marrow assessment showing megaloblastic anaemia in association with erythroblasts with iron-filled mitochondria (ringed sideroblasts) can be helpful. Affected individuals have normal thiamine serum levels.
Newborns should be screened by distortion-product otoacoustic emissions (DPOAE) and brainstem evoked response audiometry (BERA).
TRMA is a lifelong disease requiring lifetime management and regular follow-up with a Paediatric Neurology Center Management is provided by multidisciplinary team.
Lifelong use of pharmacologic doses (50-100 mg/day) of oral thiamine (vitamin B1) in affected individuals regardless of age.
Red blood cell transfusion for severe anaemia.
Hearing loss appears irremediable and has a variable timeframe.
There is still debate on whether prenatal and early thiamine treatment in affected individuals significantly delays the onset and reduces the hearing defect; several patients diagnosed at a young age have preserved hearing with thiamine treatment since a young age. Hearing aids and palliative care are recommended.
Management includes regular haematological monitoring, glucose tolerance, urine, hearing, ophthalmologic and cardiac assessment.
Genetic counselling is highly recommended for family planning and evaluation of at-risk family members such as siblings.