{"Name":"Megaloblastic anemia, thiamine-responsive, with diabetes mellitus and sensorineural deafness","DiseaseID__c":"GARD:0009210","id":9210,"encodedName":"megaloblastic-anemia-thiamine-responsive-with-diabetes-mellitus-and-sensorineural-deafness","IsDeleted":false,"Disease_Name_Full__c":"Megaloblastic anemia, thiamine-responsive, with diabetes mellitus and sensorineural deafness","Xref_IDs__c":"237617006; C0342287; C536510; DOID:0090117; MEDGEN:83338; MONDO:0009575; OMIM:249270; ORPHA:49827","USA_Estimate__c":"1,000","No_of_Specialist_Tagsa__c":5,"No_of_ClinGen_records__c":0,"No_of_GeneReviews__c":0,"No_of_HHS_records__c":1,"World_Estimate__c":"1 to 8,000","No_of_HRSA_records__c":0,"Evidence_Based_Score__c":1,"No_of_Disease_Descriptions__c":4,"Disease_Characteristics_Score__c":6,"No_of_Age_at_Onset__c":1,"Description_Source__c":"MONDO:0009575","Disease_Description__c":"Thiamine-responsive megaloblastic anemia (TRMA) is characterized by a triad of megaloblastic anemia, non-type I diabetes mellitus, and sensorineural deafness.","GARD_Name__c":"Megaloblastic anemia, thiamine-responsive, with diabetes mellitus and sensorineural deafness","GARD_Synonym__c":"rogers syndrome; thiamine metabolism dysfunction syndrome 1; thiamine metabolism dysfunction syndrome 1 (megaloblastic anemia, diabetes mellitus, and deafness type); thiamine-responsive anaemia syndrome; thiamine-responsive anemia syndrome; thiamine-responsive megaloblastic anaemia with diabetes mellitus and sensorineural deafness; thiamine-responsive megaloblastic anemia syndrome; thiamine-responsive megaloblastic anemia with diabetes mellitus and sensorineural deafness; thiamine-responsive megaloblastic anemia with diabetes mellitus and sensorineural hearing loss; thiamine-responsive myelodysplasia; thmd1; trma","Curated_Disease_Description_Source__c":"GARD:0009210","Curated_Disease_Description__c":"Thiamine-responsive megaloblastic anemia syndrome (TRMA) is a rare condition that is 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 red blood cells that are present 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 TRMA typically develop megaloblastic anemia between infancy and adolescence. TRMA is called 'thiamine-responsive' because the anemia can be treated with daily doses of vitamin B1 (thiamine). In people with TRMA, hearing loss typically develops during early childhood and is caused by abnormalities of the inner ear (sensorineural hearing loss). The hearing loss usually worsens over time. It remains unclear whether treatment with thiamine can improve hearing or delay hearing loss in people with TRMA. People with TRMA often develop diabetes mellitus, a condition in which glucose levels can become dangerously high, at an early age. Although some individuals with TRMA develop diabetes during childhood, they do not have the autoimmune form of diabetes that typically develops in children, called type 1 diabetes. People with TRMA usually require insulin to treat their diabetes. In some cases, treatment with thiamine may delay the onset of diabetes or reduce the amount of insulin a person needs. Some individuals with TRMA have abnormalities of the eye, including optic atrophy, which is the degeneration (atrophy) of the nerves that carry information from the eyes to the brain. Additional features of this condition may include heart and blood vessel (cardiovascular) problems, intellectual disabilities, behavioral changes, and seizures.","Curated_USA_Estimate_Source__c":null,"Curated_USA_Estimate__c":"1,000","Age_at_Onset_Snippet_Text__c":"as a Child","SourceID__c":"ORPHA:49827","Deprecated__c":"No","Disease_Concept_Type__c":"Rare Disease Entity","MONDO_ID__c":"MONDO:0009575","ORPHANET_ID__c":"ORPHA:49827","Replaced_By_ID__c":null,"Display_Spanish_Disease_Name__c":"Síndrome de anemia megaloblástica sensible a la tiamina","Spanish_Description_Source__c":"ORPHA:49827","Spanish_Description__c":"La anemia megaloblástica sensible a tiamina (AMST se caracteriza por la triada de anemia megaloblástica, diabetes mellitus no tipo 1 y sordera neurosensorial.","Spanish_Disease_Name__c":"síndrome de anemia megaloblástica sensible a la tiamina","Spanish_GARD_Synonym__c":"anemia megaloblástica sensible a la tiamina con diabetes mellitus e hipoacusia neurosensorial; anemia megaloblástica sensible a la tiamina con diabetes mellitus y sordera neurosensorial; síndrome de rogers; trma","Category_Linearization__c":"ORPHA:97992","icd10_id__c":null,"mesh_id__c":null,"omim_id__c":null,"snomed_id__c":null,"umls_id__c":null,"GARD_Disease__c":[{"Curated_Disease_Description__c":"Thiamine-responsive megaloblastic anemia syndrome (TRMA) is a rare condition that is 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 red blood cells that are present 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 TRMA typically develop megaloblastic anemia between infancy and adolescence. TRMA is called 'thiamine-responsive' because the anemia can be treated with daily doses of vitamin B1 (thiamine). In people with TRMA, hearing loss typically develops during early childhood and is caused by abnormalities of the inner ear (sensorineural hearing loss). The hearing loss usually worsens over time. It remains unclear whether treatment with thiamine can improve hearing or delay hearing loss in people with TRMA. People with TRMA often develop diabetes mellitus, a condition in which glucose levels can become dangerously high, at an early age. Although some individuals with TRMA develop diabetes during childhood, they do not have the autoimmune form of diabetes that typically develops in children, called type 1 diabetes. People with TRMA usually require insulin to treat their diabetes. In some cases, treatment with thiamine may delay the onset of diabetes or reduce the amount of insulin a person needs. Some individuals with TRMA have abnormalities of the eye, including optic atrophy, which is the degeneration (atrophy) of the nerves that carry information from the eyes to the brain. Additional features of this condition may include heart and blood vessel (cardiovascular) problems, intellectual disabilities, behavioral changes, and seizures.","Curated_Disease_Description_Source__c":"GARD:0009210","GARD_Synonym__c":"rogers syndrome; thiamine metabolism dysfunction syndrome 1; thiamine metabolism dysfunction syndrome 1 (megaloblastic anemia, diabetes mellitus, and deafness type); thiamine-responsive anaemia syndrome; thiamine-responsive anemia syndrome; thiamine-responsive megaloblastic anaemia with diabetes mellitus and sensorineural deafness; thiamine-responsive megaloblastic anemia syndrome; thiamine-responsive megaloblastic anemia with diabetes mellitus and sensorineural deafness; thiamine-responsive megaloblastic anemia with diabetes mellitus and sensorineural hearing loss; thiamine-responsive myelodysplasia; thmd1; trma","Name":"Megaloblastic anemia, thiamine-responsive, with diabetes mellitus and sensorineu","Curated_USA_Estimate__c":"1,000","estimateUsa":"1,000"}],"Organization_Supported_Diseases__c":[{"Account_Name__c":"The National Center for Monogenic Diabetes at the University of Chicago","Website__c":"https://monogenicdiabetes.uchicago.edu/"},{"Account_Name__c":"International Society for Pediatric and Adolescent Diabetes","Website__c":"https://www.ispad.org/"}],"GARD_Disease_Tag__c":[{"Tag_Name__c":"Genetics","Tag_Category__c":"Cause;Disease Category;Specialist","category_description":"Genetic diseases affect the DNA, or genetic instructions, which directs how tissues, organs, and body systems function.","curated_tag_name":"Genetic diseases"},{"Tag_Name__c":"Endocrine","Tag_Category__c":"Disease Category;Specialist","category_description":"Endocrine diseases affect hormone production or how the body responds to a specific hormone(s).","curated_tag_name":"Endocrine diseases"},{"Tag_Name__c":"Hematology","Tag_Category__c":"Disease Category;Specialist","category_description":"Blood diseases affect the blood or blood-forming organs, including red blood cells, white blood cells, platelets, plasma, and bone marrow.","curated_tag_name":"Blood diseases"},{"Tag_Name__c":"Inborn Errors of Metabolism","Tag_Category__c":"Cause;Disease Category","category_description":"Inherited metabolic diseases, or inborn errors of metabolism, are a group of genetic diseases that affect the ability of the body's cells to convert food into energy.","curated_tag_name":"Inherited metabolic diseases"},{"Tag_Name__c":"Congenital Abnormality","Tag_Category__c":"Disease Category","category_description":"Birth defects are structural changes present at birth that can affect almost any part of the body, including how the body looks, works, or both.","curated_tag_name":"Birth defects"},{"Tag_Name__c":"Otolaryngology","Tag_Category__c":"Specialist"},{"Tag_Name__c":"Pediatrics","Tag_Category__c":"Specialist"}],"Age_At_Onset__c":[{"Age_At_Onset__c":"Childhood","Provided_By__c":"ORPHA:49827"}],"Diagnosis__c":[{"Type__c":"GTR","Curie__c":"MEDGEN:C0342287"}],"External_Identifier_Disease__c":[{"URL__c":"https://raresource.nih.gov/diseases/filter/0009210","Source__c":"RareSource"},{"URL__c":"https://www.ncbi.nlm.nih.gov/books/NBK1282","Source__c":"Gene Review","Xref__c":"NBK1282"},{"URL__c":"https://browser.ihtsdotools.org/?perspective=full&conceptId1=237617006","Source__c":"C0342287; MONDO:0009575","Xref__c":"237617006"},{"URL__c":"https://www.ncbi.nlm.nih.gov/medgen/?term=83338","Source__c":"C0342287","Xref__c":"MEDGEN:83338"},{"URL__c":"https://www.omim.org/entry/249270","Source__c":"C0342287; MONDO:0009575; ORPHA:49827","Xref__c":"OMIM:249270"},{"URL__c":"https://www.ebi.ac.uk/ols4/ontologies/doid/classes?obo_id=DOID%3A0090117","Source__c":"MONDO:0009575","Xref__c":"DOID:0090117"},{"URL__c":"https://www.ncbi.nlm.nih.gov/mesh/C536510","Source__c":"MONDO:0009575","Xref__c":"C536510"},{"URL__c":"https://www.orpha.net/en/disease/detail/49827","Source__c":"C0342287; MONDO:0009575; ORPHA:49827","Xref__c":"ORPHA:49827"},{"URL__c":"https://uts.nlm.nih.gov/uts/umls/concept/C0342287","Source__c":"C0342287","Xref__c":"C0342287"},{"URL__c":"http://purl.obolibrary.org/obo/MONDO_0009575","Source__c":"GARD:0009210","Xref__c":"MONDO:0009575"},{"URL__c":"https://medlineplus.gov/genetics/condition/thiamine-responsive-megaloblastic-anemia-syndrome","Source__c":"GARD:0009210","Xref__c":"https://medlineplus.gov/genetics/condition/thiamine-responsive-megaloblastic-anemia-syndrome"}],"GARD_Disease_Gene__c":[{"GeneSymbol__c":"SLC19A2","GHR_URL__c":"https://medlineplus.gov/genetics/gene/slc19a2","Gene_Type__c":"protein-coding gene","Causal_Gene__c":true}],"Inheritance__c":["Autosomal recessive"],"GARD_Disease_Feature__c":[{"Provided_By__c":"ORPHA:49827","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"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.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001631","HPO_Synonym__c":"An opening in the wall separating the top two chambers of the heart; ASD; Atria septal defect; Atrial septum defect; Atrioseptal defect; Defect in the atrial septum; Hole in heart wall separating two upper heart chambers","HPO_Name__c":"Atrial septal defect","Feature_System__c":"Cardiovascular System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:49827","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Retinal dystrophy is an abnormality of the retina associated with a hereditary process. Retinal dystrophies are defined by their predominantly monogenic inheritance and they are frequently associated with loss or dysfunction of photoreceptor cells as a primary or secondary event.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000556","HPO_Synonym__c":"Breakdown of light-sensitive cells in back of eye","HPO_Name__c":"Retinal dystrophy","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:49827","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0006671","HPO_Name__c":"Paroxysmal atrial tachycardia","Feature_System__c":"Cardiovascular System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:49827","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002014","HPO_Synonym__c":"Diarrhea; Watery stool","HPO_Name__c":"Diarrhea","Feature_System__c":"Digestive System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:49827","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"A group of abnormalities characterized by hyperglycemia and glucose intolerance.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000819","HPO_Name__c":"Diabetes mellitus","Feature_System__c":"Endocrine System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:49827","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Abnormally pale skin.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000980","HPO_Name__c":"Pallor","Feature_System__c":"Skin System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:49827","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"A height below that which is expected according to age and sex norms. Although there is no universally accepted definition of short stature, many refer to \\\"short stature\\\" as height more than 2 standard deviations below the mean for age and sex (or below the 3rd percentile for age and sex dependent norms).","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0004322","HPO_Synonym__c":"Decreased body height; Height less than 3rd percentile; Short stature; Small stature; Stature below 3rd percentile","HPO_Name__c":"Short stature","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:49827","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000407","HPO_Synonym__c":"Hearing loss, sensorineural; Sensorineural deafness; Sensorineural hearing loss","HPO_Name__c":"Sensorineural hearing impairment","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:49827","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Loss of visual acuity (implying that vision was better at a certain time point in life). Otherwise the term reduced visual acuity should be used (or a subclass of that).","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000572","HPO_Synonym__c":"Loss of vision; Vision loss; Visual loss","HPO_Name__c":"Visual loss","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:49827","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Cephalgia, or pain sensed in various parts of the head, not confined to the area of distribution of any nerve.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002315","HPO_Synonym__c":"Headache; Headaches","HPO_Name__c":"Headache","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:49827","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"An abrupt loss of heart function.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001695","HPO_Synonym__c":"Heart stops beating","HPO_Name__c":"Cardiac arrest","Feature_System__c":"Cardiovascular System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:49827","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Sudden impairment of blood flow to a part of the brain due to occlusion or rupture of an artery to the brain.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001297","HPO_Synonym__c":"Cerebral vascular events; Cerebrovascular accident; Stroke","HPO_Name__c":"Stroke","Feature_System__c":"Nervous System; Cardiovascular System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:49827","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Abnormal sensations such as tingling, pricking, or numbness of the skin with no apparent physical cause.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0003401","HPO_Synonym__c":"Paresthesias; Pins and needles feeling; Tingling","HPO_Name__c":"Paresthesia","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:49827","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"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.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001635","HPO_Synonym__c":"Cardiac failure; Cardiac failures; Cardiac insufficiency; CHF; Chronic heart failure; Heart failure","HPO_Name__c":"Congestive heart failure","Feature_System__c":"Cardiovascular System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:49827","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"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.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000648","HPO_Synonym__c":"Optic nerve atrophy; Optic-nerve degeneration","HPO_Name__c":"Optic atrophy","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:49827","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"A state of fatigue, either physical or mental slowness and sluggishness, with difficulties in initiating or performing simple tasks. Distinguished from apathy which implies indifference and a lack of desire or interest in the task. A person with lethargy may have the desire, but not the energy to engage in personal or socially relevant tasks.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001254","HPO_Synonym__c":"Dullness; Inaction; Inactivity; Languor; Lethargy; Slowness; Torpor","HPO_Name__c":"Lethargy","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:49827","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Anemia characterized by the presence of erythroblasts that are larger than normal (megaloblasts).","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001889","HPO_Name__c":"Megaloblastic anemia","Feature_System__c":"Blood and Blood-Forming Tissue","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:49827","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Lack of desire to eat (loss of appetite).","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002039","HPO_Synonym__c":"Anorexia; Deliberately not eating; Obsessive dieting; Refusing to eat","HPO_Name__c":"Anorexia","Feature_System__c":"Digestive System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:49827","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"A hole between the two bottom chambers (ventricles) of the heart. The defect is centered around the most superior aspect of the ventricular septum.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001629","HPO_Synonym__c":"Hole in heart wall separating two lower heart chambers; Ventricular septal defects; Ventriculoseptal defect; VSD","HPO_Name__c":"Ventricular septal defect","Feature_System__c":"Cardiovascular System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:49827","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"A reduction in the number of circulating thrombocytes.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001873","HPO_Synonym__c":"Low platelet count","HPO_Name__c":"Thrombocytopenia","Feature_System__c":"Blood and Blood-Forming Tissue","HPO_Feature_Type__c":"Symptom"}}],"tags":{"Cause":["Genetics","Inborn Errors of Metabolism"],"Disease Category":["Genetics","Endocrine","Hematology","Inborn Errors of Metabolism","Congenital Abnormality"],"Specialist":["Genetics","Endocrine","Hematology","Otolaryngology","Pediatrics"]},"synonyms":["rogers syndrome"," thiamine metabolism dysfunction syndrome 1"," thiamine metabolism dysfunction syndrome 1 (megaloblastic anemia, diabetes mellitus, and deafness type)"," thiamine-responsive anaemia syndrome"," thiamine-responsive anemia syndrome"," thiamine-responsive megaloblastic anaemia with diabetes mellitus and sensorineural deafness"," thiamine-responsive megaloblastic anemia syndrome"," thiamine-responsive megaloblastic anemia with diabetes mellitus and sensorineural deafness"," thiamine-responsive megaloblastic anemia with diabetes mellitus and sensorineural hearing loss"," thiamine-responsive myelodysplasia"," thmd1"," trma"]}