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Megaloblastic anemia, thiamine-responsive, with diabetes mellitus and sensorineural deafness(TRMA)

MedGen UID:
83338
Concept ID:
C0342287
Congenital Abnormality
Synonyms: Rogers syndrome; THIAMINE METABOLISM DYSFUNCTION SYNDROME 1 (MEGALOBLASTIC ANEMIA, DIABETES MELLITUS, AND DEAFNESS TYPE); Thiamine responsive megaloblastic anemia syndrome; Thiamine-responsive anemia syndrome; Thiamine-Responsive Megaloblastic Anemia Syndrome; Thiamine-responsive myelodysplasia; TRMA
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Autosomal recessive inheritance refers to genetic conditions that occur only when mutations are present in both copies of a given gene (i.e., the person is homozygous for a mutation, or carries two different mutations of the same gene, a state referred to as compound heterozygosity).
SNOMED CT: Megaloblastic anemia, thiamine-responsive, with diabetes mellitus and sensorineural deafness (237617006); Rogers syndrome (237617006)
 
Gene: SLC19A2
Cytogenetic location: 1q24.2
OMIM®: 249270
Orphanet: ORPHA49827

Disease characteristics

Thiamine-responsive megaloblastic anemia syndrome (TRMA) is characterized by megaloblastic anemia, sensorineural hearing loss, and diabetes mellitus. Onset of megaloblastic anemia is between infancy and adolescence. The anemia is corrected with pharmacologic doses of thiamine (vitamin B1) (25-75 mg/day compared to US RDA of 1.5 mg/day). However, the red cells remain macrocytic. The anemia can recur when thiamine is withdrawn. Progressive sensorineural hearing loss has generally been early and can be detected in toddlers; hearing loss is irreversible and may not be prevented by thiamine treatment. The diabetes mellitus is non-type I in nature, with age of onset from infancy to adolescence.  [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  Diagnosis  |  Clinical Description  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  References  |  Chapter Notes
Authors:
Kimihiko Oishi  |  George A Diaz   view full author information

Additional descriptions

From OMIM
Thiamine-responsive megaloblastic anemia syndrome comprises megaloblastic anemia, diabetes mellitus, and sensorineural deafness. Onset is typically between infancy and adolescence, but all of the cardinal findings are often not present initially. The anemia, and sometimes the diabetes, improves with high doses of thiamine. Other more variable features include optic atrophy, congenital heart defects, short stature, and stroke (summary by Bergmann et al., 2009). Genetic Heterogeneity of Disorders Due to Thiamine Metabolism Dysfunction See also episodic encephalopathies due to defects in thiamine metabolism: biotin-responsive basal ganglia disease (THMD2; 607483), caused by mutation in the SLC19A3 gene (606152) on chromosome 2q; Amish lethal microcephaly (THMD3; 607196) and bilateral striatal necrosis and progressive polyneuropathy (THMD4; 613710), both caused by mutation in the SLC25A19 gene (606521) on chromosome 17q25; and THMD5 (614458), caused by mutation in the TPK1 gene (606370) on chromosome 7q34.  http://www.omim.org/entry/249270
From GHR
Thiamine-responsive megaloblastic anemia syndrome is a rare condition characterized by hearing loss, diabetes, and a blood disorder called megaloblastic anemia. Megaloblastic anemia occurs when a person has a low number of red blood cells (anemia), and the remaining red blood cells are larger than normal (megaloblastic). 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 feet. Individuals with thiamine-responsive megaloblastic anemia syndrome begin to show symptoms of megaloblastic anemia between infancy and adolescence. This syndrome is called "thiamine-responsive" because the anemia can be treated with high doses of vitamin B1 (thiamine). People with thiamine-responsive megaloblastic anemia syndrome develop hearing loss caused by abnormalities of the inner ear (sensorineural hearing loss) during early childhood. It remains unclear whether thiamine treatment can improve hearing or prevent hearing loss. Diabetes becomes apparent in affected individuals sometime between infancy and adolescence. Although these individuals develop diabetes during childhood, they do not have the form of the disease that develops most often in children, called type 1 (autoimmune) diabetes. People with thiamine-responsive megaloblastic anemia syndrome usually require insulin to treat their diabetes. In some cases, treatment with thiamine can reduce the amount of insulin a person needs. Some individuals with thiamine-responsive megaloblastic anemia syndrome develop optic atrophy, which is the degeneration (atrophy) of the nerves that carry information from the eyes to the brain. Heart and blood vessel (cardiovascular) problems such as heart rhythm abnormalities and heart defects have also been reported in some people with this syndrome.  http://ghr.nlm.nih.gov/condition/thiamine-responsive-megaloblastic-anemia-syndrome

Clinical features

Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
Cryptorchidism
MedGen UID:
504309
Concept ID:
CN000029
Finding
Absence of one or both testes from the scrotum owing to failure of the testis or testes to descend through the inguinal canal to the testis.
Aminoaciduria
MedGen UID:
425142
Concept ID:
CN003029
Finding
An increased concentration of an amino acid in the urine.
Visual impairment
MedGen UID:
22663
Concept ID:
C0042798
Finding
Vision considered to be inferior to normal vision as represented by accepted standards of acuity, field of vision, or motility. Low vision generally refers to visual disorders that are caused by diseases that cannot be corrected by refraction (e.g., MACULAR DEGENERATION; RETINITIS PIGMENTOSA; DIABETIC RETINOPATHY, etc.).
Abnormal retinal pigmentation
MedGen UID:
350681
Concept ID:
C1862475
Finding
Nystagmus
MedGen UID:
409575
Concept ID:
C1963184
Finding
Retinal degeneration
MedGen UID:
504488
Concept ID:
CN000512
Finding
A deterioration of the retina. This nonspecific term is retained here because of its wide use in the literature, but if possible new annotations should indicate the precise type of retinal abnormality.
Cone-rod dystrophy
MedGen UID:
504490
Concept ID:
CN000514
Finding
Visual loss
MedGen UID:
504502
Concept ID:
CN000537
Finding
Loss of visual acuity (implying that vision was better at a certain timepoint in live - otherwise the term is impaired vision or a subclass of that).
Optic atrophy
MedGen UID:
504537
Concept ID:
CN000609
Finding
Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.
Sensorineural hearing impairment
MedGen UID:
504436
Concept ID:
CN000380
Finding
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.
Stroke
MedGen UID:
340407
Concept ID:
C1849743
Finding
Seizures
MedGen UID:
409523
Concept ID:
C1959629
Finding
Ataxia
MedGen UID:
504767
Concept ID:
CN001146
Finding
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- oder overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Global developmental delay
MedGen UID:
504774
Concept ID:
CN001157
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Cerebral ischemia
MedGen UID:
505309
Concept ID:
CN002398
Finding
Type I diabetes mellitus
MedGen UID:
334999
Concept ID:
C1844664
Finding
Diabetes mellitus
MedGen UID:
504609
Concept ID:
CN000766
Finding
A group of abnormalities characterized by hyperglycemia and glucose intolerance.
Gastroesophageal reflux
MedGen UID:
505057
Concept ID:
CN001828
Finding
A condition in which the stomach contents leak backwards from the stomach into the esophagus through the lower esophageal sphincter.
Abnormality of the skin
MedGen UID:
504656
Concept ID:
CN000890
Finding
An abnormality of the skin.
Hoarse voice
MedGen UID:
504872
Concept ID:
CN001465
Finding
Hoarseness refers to a change in the pitch or quality of the voice, with the voice sounding weak, very breathy, scratchy, or husky.
Arrhythmia
MedGen UID:
66750
Concept ID:
C0237314
Finding
Stroke
MedGen UID:
340407
Concept ID:
C1849743
Finding
Ventricular septal defect
MedGen UID:
347827
Concept ID:
C1859213
Finding
Sudden cardiac death
MedGen UID:
369872
Concept ID:
C1968862
Finding
Defect in the atrial septum
MedGen UID:
504879
Concept ID:
CN001485
Finding
Atrial septal defect (ASD) is a congenital abnormality of the interatrial septum that enables blood flow between the left and right atria via the interatrial septum.
Congestive heart failure
MedGen UID:
504881
Concept ID:
CN001488
Finding
The presence of an abnormality of cardiac function that is responsible for the failure of the heart to pump blood at a rate that is commensurate with the needs of the tissues or a state in which abnormally elevated filling pressures are required for the heart to do so. Heart failure is frequently related to a defect in myocardial contraction.
Cardiomyopathy
MedGen UID:
504883
Concept ID:
CN001491
Finding
A myocardial disorder in which the heart muscle is structurally and functionally abnormal, in the absence of coronary artery disease, hypertension, valvular disease and congenital heart disease sufficient to cause the observed myocardial abnormality.
Situs inversus totalis
MedGen UID:
504917
Concept ID:
CN001542
Finding
A left-right reversal (or \
Cerebral ischemia
MedGen UID:
505309
Concept ID:
CN002398
Finding
Congenital septal defect
MedGen UID:
505678
Concept ID:
CN004209
Finding
Thrombocytopenia
MedGen UID:
52737
Concept ID:
C0040034
Disease or Syndrome
A finding based on laboratory test results that indicate a decrease in number of platelets in a blood specimen.
Sideroblastic anemia
MedGen UID:
505008
Concept ID:
CN001740
Finding
Sideroblastic anemia results from a defect in the incorporation of iron into the heme molecule. A sideroblast is an erythroblast that has stainable deposits of iron in cytoplasm (this can be demonstrated by Prussian blue staining).
Macrocytic anemia
MedGen UID:
505031
Concept ID:
CN001784
Finding
A type of anemia characterized by increased size of erythrocytes with increased mean corpuscular volume (MCV) and increased mean corpuscular hemoglobin (MCH).
Thiamine-responsive megaloblastic anemia
MedGen UID:
428115
Concept ID:
CN004305
Finding
A type of megaloblastic anemia (i.e., anemia characterized by the presence of erythroblasts that are larger than normal) that improves upon the administration of thiamine.
Type I diabetes mellitus
MedGen UID:
334999
Concept ID:
C1844664
Finding
Diabetes mellitus
MedGen UID:
504609
Concept ID:
CN000766
Finding
A group of abnormalities characterized by hyperglycemia and glucose intolerance.
Aminoaciduria
MedGen UID:
425142
Concept ID:
CN003029
Finding
An increased concentration of an amino acid in the urine.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews
  • CROGMegaloblastic anemia, thiamine-responsive, with diabetes mellitus and sensorineural deafness

Recent clinical studies

Etiology

Setoodeh A, Haghighi A, Saleh-Gohari N, Ellard S, Haghighi A
Gene 2013 May 1;519(2):295-7. Epub 2013 Feb 20 doi: 10.1016/j.gene.2013.02.008. [Epub ahead of print] PMID: 23454484Free PMC Article
Yilmaz Agladioglu S, Aycan Z, Bas VN, Peltek Kendirci HN, Onder A
Genet Couns 2012;23(2):149-56. PMID: 22876572
Borgna-Pignatti C, Azzalli M, Pedretti S
J Pediatr 2009 Aug;155(2):295-7. doi: 10.1016/j.jpeds.2009.01.062. PMID: 19619756
Ganesh R, Ezhilarasi S, Vasanthi T, Gowrishankar K, Rajajee S
Indian J Pediatr 2009 Mar;76(3):313-4. Epub 2009 Apr 6 doi: 10.1007/s12098-009-0058-5. [Epub ahead of print] PMID: 19347672
Valerio G, Franzese A, Poggi V, Tenore A
Diabetes Care 1998 Jan;21(1):38-41. PMID: 9538968

Diagnosis

Yilmaz Agladioglu S, Aycan Z, Bas VN, Peltek Kendirci HN, Onder A
Genet Couns 2012;23(2):149-56. PMID: 22876572
Bay A, Keskin M, Hizli S, Uygun H, Dai A, Gumruk F
Int J Hematol 2010 Oct;92(3):524-6. Epub 2010 Sep 11 doi: 10.1007/s12185-010-0681-y. [Epub ahead of print] PMID: 20835854
Borgna-Pignatti C, Azzalli M, Pedretti S
J Pediatr 2009 Aug;155(2):295-7. doi: 10.1016/j.jpeds.2009.01.062. PMID: 19619756
Ganesh R, Ezhilarasi S, Vasanthi T, Gowrishankar K, Rajajee S
Indian J Pediatr 2009 Mar;76(3):313-4. Epub 2009 Apr 6 doi: 10.1007/s12098-009-0058-5. [Epub ahead of print] PMID: 19347672
Yeşilkaya E, Bideci A, Temizkan M, Kaya Z, Camurdan O, Koç A, Bozkaya D, Koçak U, Cinaz P
J Trop Pediatr 2009 Aug;55(4):265-7. Epub 2008 Jul 9 doi: 10.1093/tropej/fmn060. [Epub ahead of print] PMID: 18614593

Therapy

Yilmaz Agladioglu S, Aycan Z, Bas VN, Peltek Kendirci HN, Onder A
Genet Couns 2012;23(2):149-56. PMID: 22876572
Bay A, Keskin M, Hizli S, Uygun H, Dai A, Gumruk F
Int J Hematol 2010 Oct;92(3):524-6. Epub 2010 Sep 11 doi: 10.1007/s12185-010-0681-y. [Epub ahead of print] PMID: 20835854
Borgna-Pignatti C, Azzalli M, Pedretti S
J Pediatr 2009 Aug;155(2):295-7. doi: 10.1016/j.jpeds.2009.01.062. PMID: 19619756
Ganesh R, Ezhilarasi S, Vasanthi T, Gowrishankar K, Rajajee S
Indian J Pediatr 2009 Mar;76(3):313-4. Epub 2009 Apr 6 doi: 10.1007/s12098-009-0058-5. [Epub ahead of print] PMID: 19347672
Yeşilkaya E, Bideci A, Temizkan M, Kaya Z, Camurdan O, Koç A, Bozkaya D, Koçak U, Cinaz P
J Trop Pediatr 2009 Aug;55(4):265-7. Epub 2008 Jul 9 doi: 10.1093/tropej/fmn060. [Epub ahead of print] PMID: 18614593

Prognosis

Srikrupa NN, Meenakshi S, Arokiasamy T, Murali K, Soumittra N
Ophthalmic Genet 2014 Jun;35(2):119-24. Epub 2013 May 2 doi: 10.3109/13816810.2013.793363. [Epub ahead of print] PMID: 23638917
Yilmaz Agladioglu S, Aycan Z, Bas VN, Peltek Kendirci HN, Onder A
Genet Couns 2012;23(2):149-56. PMID: 22876572
Borgna-Pignatti C, Azzalli M, Pedretti S
J Pediatr 2009 Aug;155(2):295-7. doi: 10.1016/j.jpeds.2009.01.062. PMID: 19619756
Ganesh R, Ezhilarasi S, Vasanthi T, Gowrishankar K, Rajajee S
Indian J Pediatr 2009 Mar;76(3):313-4. Epub 2009 Apr 6 doi: 10.1007/s12098-009-0058-5. [Epub ahead of print] PMID: 19347672
Valerio G, Franzese A, Poggi V, Tenore A
Diabetes Care 1998 Jan;21(1):38-41. PMID: 9538968

Clinical prediction guides

Srikrupa NN, Meenakshi S, Arokiasamy T, Murali K, Soumittra N
Ophthalmic Genet 2014 Jun;35(2):119-24. Epub 2013 May 2 doi: 10.3109/13816810.2013.793363. [Epub ahead of print] PMID: 23638917
Pichler H, Zeitlhofer P, Dworzak MN, Diakos C, Haas OA, Kager L
Eur J Pediatr 2012 Nov;171(11):1711-5. Epub 2012 May 11 doi: 10.1007/s00431-012-1730-8. [Epub ahead of print] PMID: 22576805
Meire FM, Van Genderen MM, Lemmens K, Ens-Dokkum MH
Ophthalmic Genet 2000 Dec;21(4):243-50. PMID: 11135496
Raz T, Barrett T, Szargel R, Mandel H, Neufeld EJ, Nosaka K, Viana MB, Cohen N
Hum Genet 1998 Oct;103(4):455-61. PMID: 9856490
Neufeld EJ, Mandel H, Raz T, Szargel R, Yandava CN, Stagg A, Fauré S, Barrett T, Buist N, Cohen N
Am J Hum Genet 1997 Dec;61(6):1335-41. doi: 10.1086/301642. PMID: 9399900Free PMC Article

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