MCID: THM002
MIFTS: 41

Thiamine-Responsive Megaloblastic Anemia Syndrome

Categories: Genetic diseases, Rare diseases, Metabolic diseases, Ear diseases, Endocrine diseases, Fetal diseases, Blood diseases

Aliases & Classifications for Thiamine-Responsive Megaloblastic Anemia Syndrome

MalaCards integrated aliases for Thiamine-Responsive Megaloblastic Anemia Syndrome:

Name: Thiamine-Responsive Megaloblastic Anemia Syndrome 53 12 23 24 55 71 13 51
Rogers Syndrome 53 12 23 49 24 55 71
Trma 53 12 23 49 24 55 71
Thiamine-Responsive Myelodysplasia 53 12 49 24 71
Thiamine-Responsive Anemia Syndrome 53 12 49 71
Thiamine Metabolism Dysfunction Syndrome 1 53 12 71
Thmd1 53 12 71
Megaloblastic Anemia, Thiamine-Responsive, with Diabetes Mellitus and Sensorineural Deafness 53 28
Thiamine-Responsive Megaloblastic Anemia with Diabetes Mellitus and Sensorineural Deafness 12 55
Megaloblastic Anemia Thiamine-Responsive with Diabetes Mellitus and Sensorineural Deafness 49 71
Thiamine Responsive Megaloblastic Anemia Syndrome 49 41
Thiamine-Responsive Megaloblastic Anemia 36 69
Thiamine Metabolism Dysfunction Syndrome 1 ; Thmd1 53

Characteristics:

Orphanet epidemiological data:

55
thiamine-responsive megaloblastic anemia syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood; Age of death: any age;

OMIM:

53
Inheritance:
autosomal recessive

Miscellaneous:
onset in early childhood (infancy to 6 years)
classic triad is megaloblastic anemia, diabetes, and deafness, but some patients may not have this triad
variable severity of phenotype and other features may be present
later onset associated with milder severity has been reported
anemia, diabetes, and deafness often show onset at different ages
diabetes and anemia respond to high doses of thiamine supplementation


HPO:

31
thiamine-responsive megaloblastic anemia syndrome:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Thiamine-Responsive Megaloblastic Anemia Syndrome

Genetics Home Reference : 24 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).

MalaCards based summary : Thiamine-Responsive Megaloblastic Anemia Syndrome, also known as rogers syndrome, is related to thiamine metabolism dysfunction syndrome 2 and anemia, congenital dyserythropoietic, type iii, and has symptoms including headache, diarrhea and lethargy. An important gene associated with Thiamine-Responsive Megaloblastic Anemia Syndrome is SLC19A2 (Solute Carrier Family 19 Member 2), and among its related pathways/superpathways are Metabolism of water-soluble vitamins and cofactors and Vitamin digestion and absorption. Affiliated tissues include heart and skin.

Disease Ontology : 12 An autosomal recessive disease characterized by megaloblastic anemia, non-type I diabetes mellitus, and sensorineural deafness where the anemia and sometimes diabetes is repsonsive to high doses of thiamine that has material basis in homozygous mutation in the SLC19A2 gene on chromosome 1q24.

NIH Rare Diseases : 49 Thiamine-responsive megaloblastic anemiasyndrome is a very rare condition characterized by hearing loss, diabetes, and a blood disorder called megaloblastic anemia. Affected individuals begin to show symptoms of this condition between infancy and adolescence. This syndrome is called "thiamine-responsive" because the anemia can be treated with high doses of vitamin B1 (thiamine). This condition is caused by mutations in the SLC19A2 gene and is inherited in an autosomal recessive fashion. Last updated: 11/28/2011

OMIM : 53 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). (249270)

UniProtKB/Swiss-Prot : 71 Thiamine-responsive megaloblastic anemia syndrome: An autosomal recessive disease characterized by 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.

GeneReviews: NBK1282

Related Diseases for Thiamine-Responsive Megaloblastic Anemia Syndrome

Diseases related to Thiamine-Responsive Megaloblastic Anemia Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 13)
# Related Disease Score Top Affiliating Genes
1 thiamine metabolism dysfunction syndrome 2 30.4 SLC19A1 SLC19A2
2 anemia, congenital dyserythropoietic, type iii 11.3
3 diabetes and deafness, maternally inherited 11.0
4 microcephaly, amish type 10.9
5 thiamine metabolism dysfunction syndrome 4 10.9
6 thiamine metabolism dysfunction syndrome 5 10.9
7 megaloblastic anemia 10.7
8 diabetes mellitus 10.3
9 cone-rod dystrophy 2 10.1
10 ebstein anomaly 10.1
11 patent ductus arteriosus 1 10.1
12 atrial standstill 10.1
13 beriberi 9.9

Graphical network of the top 20 diseases related to Thiamine-Responsive Megaloblastic Anemia Syndrome:



Diseases related to Thiamine-Responsive Megaloblastic Anemia Syndrome

Symptoms & Phenotypes for Thiamine-Responsive Megaloblastic Anemia Syndrome

Symptoms via clinical synopsis from OMIM:

53
Endocrine Features:
diabetes mellitus

Cardiovascular Heart:
congenital heart defects (in some patients)
ventricular septal defect (in some patients)
atrial septal defect (uncommon)
conduction defects (in some patients)
arrhythmias (in some patients)
more
Head And Neck Ears:
sensorineural deafness

Neurologic Central Nervous System:
seizures (uncommon)
developmental delay (uncommon)
stroke (uncommon)
ataxia (uncommon)

Abdomen Gastroin testinal:
gastroesophageal reflux (uncommon)

Laboratory Abnormalities:
serum thiamine is normal

Hematology:
thrombocytopenia
megaloblastic anemia
sideroblastic anemia

Head And Neck Eyes:
optic atrophy (in some patients)
nystagmus (in some patients)
maculopathy (uncommon)
cone-rod dystrophy (uncommon)
retinal degeneration (in some patients)
more
Growth Height:
short stature (in some patients)

Abdomen:
situs inversus (uncommon)

Genitourinary Internal Genitalia Male:
cryptorchidism (uncommon)


Clinical features from OMIM:

249270

Human phenotypes related to Thiamine-Responsive Megaloblastic Anemia Syndrome:

55 31 (show all 36)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 headache 55 31 hallmark (90%) Very frequent (99-80%) HP:0002315
2 diarrhea 55 31 hallmark (90%) Very frequent (99-80%) HP:0002014
3 lethargy 55 31 hallmark (90%) Very frequent (99-80%) HP:0001254
4 diabetes mellitus 55 31 hallmark (90%) Very frequent (99-80%) HP:0000819
5 sensorineural hearing impairment 55 31 hallmark (90%) Very frequent (99-80%) HP:0000407
6 optic atrophy 55 31 frequent (33%) Frequent (79-30%) HP:0000648
7 short stature 55 31 occasional (7.5%) Occasional (29-5%) HP:0004322
8 pallor 55 31 hallmark (90%) Very frequent (99-80%) HP:0000980
9 congestive heart failure 55 31 occasional (7.5%) Occasional (29-5%) HP:0001635
10 atrial septal defect 55 31 occasional (7.5%) Occasional (29-5%) HP:0001631
11 thrombocytopenia 55 31 frequent (33%) Frequent (79-30%) HP:0001873
12 anorexia 55 31 hallmark (90%) Very frequent (99-80%) HP:0002039
13 paresthesia 55 31 hallmark (90%) Very frequent (99-80%) HP:0003401
14 visual loss 55 31 occasional (7.5%) Occasional (29-5%) HP:0000572
15 ventricular septal defect 55 31 occasional (7.5%) Occasional (29-5%) HP:0001629
16 stroke 55 31 occasional (7.5%) Occasional (29-5%) HP:0001297
17 cardiac arrest 55 31 occasional (7.5%) Occasional (29-5%) HP:0001695
18 retinal dystrophy 55 31 occasional (7.5%) Occasional (29-5%) HP:0000556
19 megaloblastic anemia 55 31 hallmark (90%) Very frequent (99-80%) HP:0001889
20 paroxysmal atrial tachycardia 55 31 occasional (7.5%) Occasional (29-5%) HP:0006671
21 ataxia 31 occasional (7.5%) HP:0001251
22 seizures 31 occasional (7.5%) HP:0001250
23 nystagmus 31 HP:0000639
24 global developmental delay 31 occasional (7.5%) HP:0001263
25 gastroesophageal reflux 31 occasional (7.5%) HP:0002020
26 aminoaciduria 31 HP:0003355
27 arrhythmia 31 HP:0011675
28 cryptorchidism 31 occasional (7.5%) HP:0000028
29 cardiomyopathy 31 occasional (7.5%) HP:0001638
30 hoarse voice 31 HP:0001609
31 situs inversus totalis 31 occasional (7.5%) HP:0001696
32 abnormality of the skin 31 HP:0000951
33 retinal degeneration 31 HP:0000546
34 thiamine-responsive megaloblastic anemia 31 HP:0004860
35 sideroblastic anemia 31 HP:0001924
36 cone/cone-rod dystrophy 31 HP:0000548

Drugs & Therapeutics for Thiamine-Responsive Megaloblastic Anemia Syndrome

Search Clinical Trials , NIH Clinical Center for Thiamine-Responsive Megaloblastic Anemia Syndrome

Cochrane evidence based reviews: thiamine responsive megaloblastic anemia syndrome

Genetic Tests for Thiamine-Responsive Megaloblastic Anemia Syndrome

Genetic tests related to Thiamine-Responsive Megaloblastic Anemia Syndrome:

# Genetic test Affiliating Genes
1 Megaloblastic Anemia, Thiamine-Responsive, with Diabetes Mellitus and Sensorineural Deafness 28 SLC19A2

Anatomical Context for Thiamine-Responsive Megaloblastic Anemia Syndrome

MalaCards organs/tissues related to Thiamine-Responsive Megaloblastic Anemia Syndrome:

38
Heart, Skin

Publications for Thiamine-Responsive Megaloblastic Anemia Syndrome

Articles related to Thiamine-Responsive Megaloblastic Anemia Syndrome:

(show all 23)
# Title Authors Year
1
Infantile-onset thiamine responsive megaloblastic anemia syndrome with SLC19A2 mutation: a case report. ( 28504500 )
2017
2
Thiamine responsive megaloblastic anemia syndrome: A novel homozygous SLC19A2 gene mutation identified. ( 25707023 )
2015
3
Cochlear implant and thiamine-responsive megaloblastic anemia syndrome. ( 24658560 )
2014
4
Recurrent psychiatric manifestations in thiamine-responsive megaloblastic anemia syndrome due to a novel mutation c.63_71 delACCGCTC in the gene SLC19A2. ( 24520986 )
2014
5
Thiamine-responsive megaloblastic anemia syndrome with Ebstein anomaly: a case report. ( 24357267 )
2013
6
Thiamine responsive megaloblastic anemia syndrome associated with patent ductus arteriosus: First case report from Kashmir Valley of the Indian subcontinent. ( 22837935 )
2012
7
Thiamine-responsive megaloblastic anemia syndrome: a novel mutation. ( 22876572 )
2012
8
Thiamine-responsive megaloblastic anemia syndrome with atrial standstill: a case report. ( 21285901 )
2011
9
Thiamine-responsive megaloblastic anemia syndrome. ( 20835854 )
2010
10
Thiamine-responsive megaloblastic anemia syndrome: long term follow-up. ( 19619756 )
2009
11
Thiamine responsive megaloblastic anemia syndrome. ( 19347672 )
2009
12
A novel mutation in the SLC19A2 gene in a Turkish female with thiamine-responsive megaloblastic anemia syndrome. ( 18614593 )
2009
13
Novel mutation in the SLC19A2 gene in an African-American female with thiamine-responsive megaloblastic anemia syndrome. ( 14994241 )
2004
14
Cardiac manifestations in thiamine-responsive megaloblastic anemia syndrome. ( 14627317 )
2003
15
Thiamine-responsive megaloblastic anemia syndrome: a disorder of high-affinity thiamine transport. ( 11358373 )
2001
16
Acute ischemic stroke in a young woman with the thiamine-responsive megaloblastic anemia syndrome. ( 10720020 )
2000
17
Thiamine-responsive megaloblastic anemia syndrome (TRMA) with cone-rod dystrophy. ( 11135496 )
2000
18
Localization of the thiamine-responsive megaloblastic anemia syndrome locus to a 1.4-cM region of 1q23. ( 10066388 )
1999
19
Defective high-affinity thiamine transporter leads to cell death in thiamine-responsive megaloblastic anemia syndrome fibroblasts. ( 10074490 )
1999
20
Long-term follow-up of diabetes in two patients with thiamine-responsive megaloblastic anemia syndrome. ( 9538968 )
1998
21
Refined mapping of the gene for thiamine-responsive megaloblastic anemia syndrome and evidence for genetic homogeneity. ( 9856490 )
1998
22
Localization of the gene for thiamine-responsive megaloblastic anemia syndrome, on the long arm of chromosome 1, by homozygosity mapping. ( 9399900 )
1997
23
Thiamine-Responsive Megaloblastic Anemia Syndrome ( 20301459 )
1993

Variations for Thiamine-Responsive Megaloblastic Anemia Syndrome

UniProtKB/Swiss-Prot genetic disease variations for Thiamine-Responsive Megaloblastic Anemia Syndrome:

71
# Symbol AA change Variation ID SNP ID
1 SLC19A2 p.Gly172Asp VAR_010248 rs28937595
2 SLC19A2 p.Asp93His VAR_010249
3 SLC19A2 p.Ser143Phe VAR_010250 rs761957186

ClinVar genetic disease variations for Thiamine-Responsive Megaloblastic Anemia Syndrome:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 SLC19A2 NM_006996.2(SLC19A2): c.484C> T (p.Arg162Ter) single nucleotide variant Pathogenic rs74315373 GRCh37 Chromosome 1, 169446716: 169446716
2 SLC19A2 SLC19A2, 1-BP DEL, 724C deletion Pathogenic
3 SLC19A2 NM_006996.2(SLC19A2): c.515G> A (p.Gly172Asp) single nucleotide variant Pathogenic rs28937595 GRCh37 Chromosome 1, 169446685: 169446685
4 SLC19A2 NM_006996.2(SLC19A2): c.750G> A (p.Trp250Ter) single nucleotide variant Pathogenic rs74315374 GRCh37 Chromosome 1, 169446450: 169446450
5 SLC19A2 SLC19A2, 1-BP DEL, 885T deletion Pathogenic
6 SLC19A2 SLC19A2, 2-BP DEL, 1147GT deletion Pathogenic
7 SLC19A2 SLC19A2, 1-BP INS, 242A insertion Pathogenic
8 SLC19A2 SLC19A2, 2-BP DEL, 429TT deletion Pathogenic
9 SLC19A2 NM_006996.2(SLC19A2): c.1074G> A (p.Trp358Ter) single nucleotide variant Pathogenic rs74315375 GRCh37 Chromosome 1, 169438031: 169438031
10 SLC19A2 NM_006996.2(SLC19A2): c.152C> T (p.Pro51Leu) single nucleotide variant Pathogenic rs121908540 GRCh37 Chromosome 1, 169454853: 169454853

Expression for Thiamine-Responsive Megaloblastic Anemia Syndrome

Search GEO for disease gene expression data for Thiamine-Responsive Megaloblastic Anemia Syndrome.

Pathways for Thiamine-Responsive Megaloblastic Anemia Syndrome

GO Terms for Thiamine-Responsive Megaloblastic Anemia Syndrome

Biological processes related to Thiamine-Responsive Megaloblastic Anemia Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 vitamin transport GO:0051180 8.96 SLC19A1 SLC19A2
2 folic acid transport GO:0015884 8.62 SLC19A1 SLC19A2

Molecular functions related to Thiamine-Responsive Megaloblastic Anemia Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 folic acid transmembrane transporter activity GO:0008517 8.62 SLC19A1 SLC19A2

Sources for Thiamine-Responsive Megaloblastic Anemia Syndrome

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16 ExPASy
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65 SNOMED-CT via HPO
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