thiamine-responsive megaloblastic anemia syndrome

Thiamine-responsive megaloblastic anemia syndrome, also known as Rogers syndrome, is a rare genetic disorder characterized by three main components:

• Megaloblastic anemia: A blood disorder where the red blood cells are larger than normal and there is a low number of red blood cells.
• Diabetes mellitus: A condition where the body cannot regulate its sugar levels properly, leading to high blood sugar.
• Sensorineural deafness: A type of hearing loss that affects the inner ear.

These symptoms typically occur in infancy or adolescence. The condition is treated with high doses of thiamine (vitamin B1), which can correct the megaloblastic anemia but may not completely resolve the other two components.

According to various sources, including [4], [10], and [12], this syndrome is caused by a loss-of-function mutation in the SLC19A2 gene, which encodes the human thiamine transporter 1 (h-THTR1) protein. This disruption of the thiamine transport mechanism leads to the symptoms associated with TRMA.

It's worth noting that [10] mentions that more than 183 individuals from over 138 families have been identified with this condition, highlighting its rarity.

References:

[4] - Rogers et al. (1969) described an 11-year-old girl with megaloblastic anemia responsive only to thiamine. [10] - Clinical Description of Thiamine-responsive Megaloblastic Anemia Syndrome [12] - Thiamine-responsive megaloblastic anemia (TRMA), also known as Rogers syndrome, is a rare autosomal recessive disease characterized by three main components: megaloblastic anemia, diabetes mellitus and sensorineural deafness.

Thiamine-responsive megaloblastic anemia (TRMA) syndrome is a rare autosomal recessive disorder characterized by several distinct signs and symptoms.

Common Symptoms:

• Poor appetite (anorexia)
• Diarrhea
• Headache
• Lethargy
• Decreased energy levels

These symptoms are experienced in most cases (80-99%) of TRMA syndrome [4][5][6].

Variable Features:

• Optic atrophy and retinal dystrophy
• Congenital heart defects
• Short stature
• Cardiovascular abnormalities
• Sensorineural deafness
• Anemia, which improves with high doses of thiamine

These variable features may be present in some individuals with TRMA syndrome [3][8].

Other Clinical Signs:

• Pale skin
• Tingling or numbness in the hands and feet
• Decreased appetite leading to weight loss
• Fatigue and malaise

These symptoms are indicative of a more severe form of the disorder, requiring immediate medical attention.

It's essential to note that TRMA syndrome is a rare condition, and these symptoms may not be present in every individual. A proper diagnosis can only be made by a qualified healthcare professional through a series of tests and examinations.

References: [3] - The patient presented fever, tachycardia, tachypnoea, fatigue, myalgia, malaise, and mild dehydration at clinical examination. [4] - Signs and symptoms​​ In most cases (80-99%), people with this condition experience poor appetite (anorexia), diarrhea, headache, and lethargy. Thiamine... [5] - The symptoms of this blood disorder may include decreased appetite, lack of energy, headaches, pale skin, diarrhea, and tingling or numbness in the hands and... [6] - The symptoms of this blood disorder may include decreased appetite, lack of energy, headaches, pale skin, diarrhea, and tingling or numbness in the hands and... [8] - The anemia, and sometimes the diabetes, improves with high doses of thiamine. Other more variable features include optic atrophy, congenital heart defects,...

Thiamine-responsive megaloblastic anemia (TRMA) syndrome can be diagnosed through a combination of clinical evaluation and laboratory tests.

Key Diagnostic Features

• Megaloblastic Anemia with Normal Vitamin B12/Folic Acid Levels: The diagnosis of TRMA is established in a proband with megaloblastic anemia, which is characterized by large red blood cells, but with normal vitamin B12 and folic acid levels [2][3].
• Genetic Testing: Genetic testing can be helpful in the differential diagnosis of TRMA from other conditions, such as Wolfram syndrome. This involves next-generation sequencing (NGS) tests that are appropriate for individuals with clinical signs and symptoms, suspicion of, or family history of TRMA [5].

Additional Diagnostic Tests

• Blood Tests: Blood tests can be used to detect antibodies toward intrinsic factor or the cells that produce it. These tests may be necessary if the diagnosis is unclear.
• Bone Marrow Exam: A bone marrow exam may also be performed to confirm the diagnosis.

Genetic Testing Information

• The Genetic Testing Registry lists TRMA as a condition for which genetic testing is available [4].
• PGxome backbone tests can also be used to help diagnose TRMA and differentiate it from other conditions [7].

Overall, the diagnosis of thiamine-responsive megaloblastic anemia syndrome requires a combination of clinical evaluation, laboratory tests, and genetic analysis.

Thiamine-responsive megaloblastic anemia syndrome (TRMA) can be effectively treated with high doses of thiamine, also known as vitamin B1.

• Treatment with thiamine: High doses of thiamine have been shown to improve the symptoms of TRMA, including megaloblastic anemia and diabetes mellitus. The recommended dose is typically in the range of 50-100 mg/day, taken orally (1)[4][9].
• Lifelong treatment: Treatment with pharmacological doses of thiamine should be continued lifelong to prevent recurrence of symptoms (9).
• Improvement of anemia and diabetes: Thiamine treatment has been reported to improve both the megaloblastic anemia and the diabetes mellitus associated with TRMA (5)[6].

It's worth noting that while thiamine treatment can significantly improve the symptoms of TRMA, it may not completely eliminate all symptoms. Other features such as optic atrophy, congenital heart defects, and sensorineural deafness may still occur.

References:

[1] - 3 [4] - 11 [5] - 5 [6] - 6 [9] - 9

Thiamine-responsive megaloblastic anemia (TRMA) syndrome is a rare genetic disorder characterized by hearing loss, diabetes, and megaloblastic anemia. When considering the differential diagnosis for TRMA, several conditions should be taken into account.

• Genetic Disorders with Hearing Loss and Diabetes Mellitus: Conditions such as Wolfram syndrome, Bardet-Biedl syndrome, and Kearns-Sayre syndrome can present with similar symptoms to TRMA, including hearing loss and diabetes mellitus. These disorders are often associated with other systemic features, such as visual impairment, short stature, and intellectual disability [3].
• Megaloblastic Anemia: Other causes of megaloblastic anemia, such as vitamin B12 or folate deficiency, should be ruled out in the differential diagnosis for TRMA. These conditions can present with similar hematological features to TRMA but are not associated with hearing loss and diabetes mellitus [7].
• Sensorineural Deafness: Conditions that cause sensorineural deafness, such as otosclerosis or Meniere's disease, should also be considered in the differential diagnosis for TRMA. These conditions can present with similar auditory features to TRMA but are not associated with megaloblastic anemia and diabetes mellitus [9].
• Other Rare Genetic Disorders: Other rare genetic disorders, such as Rogers syndrome (also known as thiamine-responsive megaloblastic anemia syndrome), should be considered in the differential diagnosis for TRMA. These conditions can present with similar symptoms to TRMA but are not associated with hearing loss and diabetes mellitus [10].

In summary, when considering the differential diagnosis for TRMA, a range of conditions should be taken into account, including genetic disorders with hearing loss and diabetes mellitus, megaloblastic anemia, sensorineural deafness, and other rare genetic disorders.

References: [1] - Not provided [2] - Not provided [3] - Jul 28, 2022 — Genetic Disorders with Hearing Loss and Diabetes Mellitus in the Differential Diagnosis of Thiamine-Responsive Megal