Thiamine-responsive megaloblastic anemia syndrome

General Information (adopted from Orphanet):

Synonyms, Signs: THIAMINE METABOLISM DYSFUNCTION SYNDROME 1 (MEGALOBLASTIC ANEMIA, DIABETES MELLITUS, AND DEAFNESS TYPE)
MEGALOBLASTIC ANEMIA, THIAMINE-RESPONSIVE, WITH DIABETES MELLITUS AND SENSORINEURAL DEAFNESS
THIAMINE-RESPONSIVE MYELODYSPLASIA
THIAMINE-RESPONSIVE ANEMIA SYNDROME
THMD1
TRMA
Thiamine-responsive megaloblastic anemia with diabetes mellitus and sensorineural deafness
rogers syndrome
Number of Symptoms 60
OrphanetNr: 49827
OMIM Id: 249270
ICD-10: D53.1
UMLs: C0342287
MeSH: C536510
MedDRA:
Snomed: 237617006

Prevalence, inheritance and age of onset:

Prevalence: < 80 cases [Orphanet]
Inheritance: Autosomal recessive
[Orphanet]
Age of onset: Childhood
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: AARSKOG SYNDROME, AUTOSOMAL DOMINANT
 -AARSKOG SYNDROME, AUTOSOMAL DOMINANT
Constitutional sideroblastic anemia
 -Rare genetic disease
 -Rare hematologic disease
Disorder of thiamin metabolism and transport
 -Rare genetic disease
Other rare diabetes mellitus
 -Rare endocrine disease
Rare genetic diabetes mellitus
 -Rare genetic disease
Syndromic genetic deafness
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
 -Rare otorhinolaryngologic disease
Vitamin B12- and folate-independent constitutional megaloblastic anemia
 -Rare genetic disease
 -Rare hematologic disease

Comment:

Monogenic form of diabetes caused by mutations in SLC19A2 (PMID:21127150)

Symptom Information: Sort by abundance 

1
(HPO:0008689) Bilateral cryptorchidism 38 / 7739
2
(HPO:0003355) Aminoaciduria 65 / 7739
3
(HPO:0000028) Cryptorchidism 347 / 7739
4
(HPO:0007703) Abnormality of retinal pigmentation Occasional [Orphanet] 21 / 7739
5
(HPO:0000510) Rod-cone dystrophy Occasional [Orphanet] 266 / 7739
6
(HPO:0000646) Amblyopia Occasional [Orphanet] 42 / 7739
7
(HPO:0000546) Retinal degeneration 61 / 7739
8
(HPO:0007754) Macular dystrophy 26 / 7739
9
(HPO:0000639) Nystagmus 555 / 7739
10
(HPO:0000618) Blindness Occasional [Orphanet] 124 / 7739
11
(HPO:0000648) Optic atrophy Frequent [Orphanet] 238 / 7739
12
(HPO:0001085) Papilledema Frequent [Orphanet] 31 / 7739
13
(HPO:0000505) Visual impairment Occasional [Orphanet] 297 / 7739
14
(HPO:0000572) Visual loss Occasional [Orphanet] 272 / 7739
15
(HPO:0000548) Cone/cone-rod dystrophy 47 / 7739
16
(HPO:0000608) Macular degeneration 36 / 7739
17
(HPO:0000407) Sensorineural hearing impairment Very frequent [Orphanet] 524 / 7739
18
(HPO:0008625) Severe sensorineural hearing impairment Very frequent [Orphanet] hallmark [HPO] 150 / 7739
19
(HPO:0008527) Congenital sensorineural hearing impairment Very frequent [Orphanet] hallmark [HPO] 165 / 7739
20
(HPO:0002066) Gait ataxia 327 / 7739
21
(HPO:0001249) Intellectual disability 1089 / 7739
22
(HPO:0001263) Global developmental delay 853 / 7739
23
(HPO:0001270) Motor delay 322 / 7739
24
(HPO:0001250) Seizures 1245 / 7739
25
(HPO:0001327) Photomyoclonic seizures 125 / 7739
26
(HPO:0001251) Ataxia 413 / 7739
27
(HPO:0002311) Incoordination 84 / 7739
28
(HPO:0000819) Diabetes mellitus 131 / 7739
29
(HPO:0100651) Type I diabetes mellitus Very frequent [Orphanet] 44 / 7739
30
(HPO:0002020) Gastroesophageal reflux 101 / 7739
31
(HPO:0003363) Abdominal situs inversus 19 / 7739
32
(HPO:0001696) Situs inversus totalis 44 / 7739
33
(HPO:0004322) Short stature Occasional [Orphanet] 1232 / 7739
34
(HPO:0003510) Severe short stature Occasional [Orphanet] 90 / 7739
35
(HPO:0011354) Generalized abnormality of skin 7 / 7739
36
(HPO:0000951) Abnormality of the skin 147 / 7739
37
(HPO:0002140) Ischemic stroke Occasional [Orphanet] rare [HPO] 70 / 7739
38
(HPO:0004760) Congenital septal defect 69 / 7739
39
(HPO:0001678) Atrioventricular block 59 / 7739
40
(HPO:0002637) Cerebral ischemia Occasional [Orphanet] 17 / 7739
41
(HPO:0001629) Ventricular septal defect 316 / 7739
42
(HPO:0001695) Cardiac arrest Occasional [Orphanet] 87 / 7739
43
(HPO:0001637) Abnormality of the myocardium 76 / 7739
44
(HPO:0001297) Stroke Occasional [Orphanet] rare [HPO] 44 / 7739
45
(HPO:0001671) Abnormality of the cardiac septa 55 / 7739
46
(HPO:0001638) Cardiomyopathy 192 / 7739
47
(HPO:0002326) Transient ischemic attack Occasional [Orphanet] 13 / 7739
48
(HPO:0030680) Abnormality of cardiovascular system morphology Occasional [Orphanet] 355 / 7739
49
(HPO:0001635) Congestive heart failure Occasional [Orphanet] 232 / 7739
50
(HPO:0011675) Arrhythmia Occasional [Orphanet] 226 / 7739
51
(HPO:0001631) Atria septal defect 274 / 7739
52
(HPO:0001645) Sudden cardiac death Occasional [Orphanet] 84 / 7739
53
(HPO:0001889) Megaloblastic anemia 28 / 7739
54
(HPO:0001972) Macrocytic anemia Very frequent [Orphanet] 26 / 7739
55
(HPO:0001924) Sideroblastic anemia 12 / 7739
56
(HPO:0001873) Thrombocytopenia Frequent [Orphanet] 224 / 7739
57
(HPO:0004860) Thiamine-responsive megaloblastic anemia 1 / 7739
58
(HPO:0001609) Hoarse voice 34 / 7739
59
(HPO:0006543) Cardiorespiratory arrest Occasional [Orphanet] 11 / 7739
60
(OMIM) Serum thiamine is normal 1 / 7739

Associated genes:

SLC19A2

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (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 ...
Clinical Description OMIM Rogers et al. (1969) described an 11-year-old girl with megaloblastic anemia responsive only to thiamine. She also had diabetes mellitus, amino aciduria, and sensorineural deafness. Viana and Carvalho (1978) described a 6-year-old girl with congenital megaloblastic anemia that responded ...
Molecular genetics OMIM By positional cloning, Labay et al. (1999) identified the SLC19A2 gene, which they called THTR1, within the critical TRMA locus region. In all affected members of 6 families segregating TRMA, they identified homozygous mutations in the SLC19A2 gene, which ...
Diagnosis GeneReviews The diagnosis of thiamine-responsive megaloblastic anemia syndrome (TRMA) is based on an obligate triad of clinical features:...
Clinical Description GeneReviews TRMA is characterized by megaloblastic anemia, sensorineural hearing loss, and diabetes mellitus....
Genotype-Phenotype Correlations GeneReviews No genotype-phenotype correlation has been discerned. Homozygous null mutations in SLC19A2, regardless of position within the gene sequence, result in TRMA, as do all of the reported missense mutations (however, bias of ascertainment may have occurred). ...
Differential Diagnosis GeneReviews Table 2. Thiamine-Responsive Dysfunction Syndrome: OMIM Phenotypic Series ...
Management GeneReviews To establish the extent of disease in an individual diagnosed with thiamine-responsive megaloblastic anemia syndrome (TRMA), the following evaluations are recommended:...
Molecular genetics GeneReviews Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED....