{"Name":"Constitutional megaloblastic anemia with severe neurologic disease","DiseaseID__c":"GARD:0011000","id":11000,"encodedName":"constitutional-megaloblastic-anemia-with-severe-neurologic-disease","IsDeleted":false,"Disease_Name_Full__c":"Constitutional megaloblastic anemia with severe neurologic disease","Xref_IDs__c":"124178006; C3151205; C565095; MEDGEN:462555; MONDO:0013456; OMIM:613839; ORPHA:319651","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":0,"World_Estimate__c":"1 to 8,000","No_of_HRSA_records__c":0,"Evidence_Based_Score__c":0,"No_of_Disease_Descriptions__c":2,"Disease_Characteristics_Score__c":7,"No_of_Age_at_Onset__c":2,"Description_Source__c":"ORPHA:319651","Disease_Description__c":null,"GARD_Name__c":"Constitutional megaloblastic anemia with severe neurologic disease","GARD_Synonym__c":"dhfr deficiency; dihydrofolate reductase deficiency; megaloblastic anemia due to dihydrofolate reductase deficiency","Curated_Disease_Description_Source__c":"OMIM:613839","Curated_Disease_Description__c":"Constitutional megaloblastic anemia with severe neurologic disease is an autosomal recessive metabolic disorder characterized by the hematologic findings of megaloblastic anemia and variable neurologic symptoms. These symptoms range from severe developmental delay and generalized seizures in infancy to childhood absence epilepsy with learning difficulties to lack of symptoms. This disease is caused by mutations in the DHFR gene.","Curated_USA_Estimate_Source__c":null,"Curated_USA_Estimate__c":"1,000","Age_at_Onset_Snippet_Text__c":"as an Infant and as a Child","SourceID__c":"ORPHA:319651","Deprecated__c":"No","Disease_Concept_Type__c":"Rare Disease Entity","MONDO_ID__c":"MONDO:0013456","ORPHANET_ID__c":"ORPHA:319651","Replaced_By_ID__c":null,"Display_Spanish_Disease_Name__c":"Anemia megaloblástica constitucional con enfermedad neurológica grave","Spanish_Description_Source__c":null,"Spanish_Description__c":null,"Spanish_Disease_Name__c":"anemia megaloblástica constitucional con enfermedad neurológica grave","Spanish_GARD_Synonym__c":"deficiencia de dhfr; deficiencia de dihidrofolato reductasa","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":"Constitutional megaloblastic anemia with severe neurologic disease is an autosomal recessive metabolic disorder characterized by the hematologic findings of megaloblastic anemia and variable neurologic symptoms. These symptoms range from severe developmental delay and generalized seizures in infancy to childhood absence epilepsy with learning difficulties to lack of symptoms. This disease is caused by mutations in the DHFR gene.","Curated_Disease_Description_Source__c":"OMIM:613839","GARD_Synonym__c":"dhfr deficiency; dihydrofolate reductase deficiency; megaloblastic anemia due to dihydrofolate reductase deficiency","Name":"Constitutional megaloblastic anemia with severe neurologic disease","Curated_USA_Estimate__c":"1,000","estimateUsa":"1,000"}],"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":"Neurology","Tag_Category__c":"Disease Category;Specialist","category_description":"Neurological diseases affect the brain, spinal cord, cranial nerves, autonomic nerves, or other peripheral nerves.","curated_tag_name":"Neurological 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":"Epilepsy","Tag_Category__c":"Account;Specialist","curated_tag_name":"Epilepsy"},{"Tag_Name__c":"Pediatrics","Tag_Category__c":"Specialist"}],"Age_At_Onset__c":[{"Age_At_Onset__c":"Childhood","Provided_By__c":"ORPHA:319651"},{"Age_At_Onset__c":"Infancy","Provided_By__c":"ORPHA:319651"}],"External_Identifier_Disease__c":[{"URL__c":"https://raresource.nih.gov/diseases/filter/0011000","Source__c":"RareSource"},{"URL__c":"https://www.ncbi.nlm.nih.gov/medgen/?term=462555","Source__c":"C3151205","Xref__c":"MEDGEN:462555"},{"URL__c":"https://uts.nlm.nih.gov/uts/umls/concept/C3151205","Source__c":"C3151205","Xref__c":"C3151205"},{"URL__c":"https://www.orpha.net/en/disease/detail/319651","Source__c":"C3151205; MONDO:0013456; ORPHA:319651","Xref__c":"ORPHA:319651"},{"URL__c":"https://browser.ihtsdotools.org/?perspective=full&conceptId1=124178006","Source__c":"MONDO:0013456","Xref__c":"124178006"},{"URL__c":"https://www.ncbi.nlm.nih.gov/mesh/C565095","Source__c":"MONDO:0013456","Xref__c":"C565095"},{"URL__c":"https://www.omim.org/entry/613839","Source__c":"C3151205; MONDO:0013456; ORPHA:319651","Xref__c":"OMIM:613839"},{"URL__c":"http://purl.obolibrary.org/obo/MONDO_0013456","Source__c":"GARD:0011000","Xref__c":"MONDO:0013456"},{"URL__c":"https://browser.ihtsdotools.org/?perspective=full&conceptId1=866092006","Source__c":"C3151205","Xref__c":"866092006"}],"GARD_Disease_Gene__c":[{"GeneSymbol__c":"DHFR","Gene_Type__c":"protein-coding gene","Causal_Gene__c":true}],"Inheritance__c":["Autosomal recessive"],"GARD_Disease_Feature__c":[{"Provided_By__c":"OMIM:613839","Feature__r":{"HPO_Description__c":"Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0011968","HPO_Synonym__c":"Decreased oral intake; Feeding difficulties; Feeding problems; Poor feeding","HPO_Name__c":"Feeding difficulties","Feature_System__c":"Digestive System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:613839","Feature__r":{"HPO_Description__c":"Abnormally increased size of the liver.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002240","HPO_Synonym__c":"Enlarged liver","HPO_Name__c":"Hepatomegaly","Feature_System__c":"Digestive System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:613839","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Larger than normal size of erythrocytes.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0005518","HPO_Synonym__c":"Erythrocyte macrocytosis; Increased MCV","HPO_Name__c":"Increased mean corpuscular volume","Feature_System__c":"Blood and Blood-Forming Tissue","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:613839","HPO_Frequency__c":"Frequent (30-79%)","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":"OMIM:613839","Feature__r":{"HPO_Description__c":"Yellow pigmentation of the skin due to bilirubin, which in turn is the result of increased bilirubin concentration in the bloodstream.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000952","HPO_Synonym__c":"Icterus; Jaundice; Yellow skin; Yellowing of the skin","HPO_Name__c":"Jaundice","Feature_System__c":"Skin System; Digestive System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:613839","Feature__r":{"HPO_Description__c":"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.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001263","HPO_Synonym__c":"Delayed cognitive development; Delayed development; Delayed developmental milestones; Delayed intellectual development; Delayed milestones; Delayed psychomotor development; Developmental delay; Developmental delay in early childhood; Developmental delay, global; Developmental retardation; GDD; Lack of psychomotor development; Motor and developmental delay; Motormental retardation; Psychomotor delay; Psychomotor development deficiency; Psychomotor development failure; Psychomotor developmental delay; Retarded development; Retarded mental development; Retarded psychomotor development","HPO_Name__c":"Global developmental delay","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:613839","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"An absence with eyelid myoclonia seizure is a type of generalized non-motor (absence) seizure characterized by forced upward jerking of the eyelids during an absence seizure.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0011149","HPO_Synonym__c":"Absence seizures with eyelid myoclonia","HPO_Name__c":"Absence seizure with eyelid myoclonia","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:613839","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":"OMIM:613839","Feature__r":{"HPO_Description__c":"Difficulty to maintain correct position of the head while standing or sitting. Infant head lag is observed when the head seems to flop around or lags posteriorly behind the trunk. Several articles have maintained that head lag should be absent by age 3 to 4 months.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002421","HPO_Synonym__c":"Delay in head control; Delay in head righting; Infant head lag; Poor head control","HPO_Name__c":"Poor head control","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:613839","Feature__r":{"HPO_Description__c":"Ataxia refers to impaired coordination of voluntary muscle movement. 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- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001251","HPO_Synonym__c":"Cerebellar ataxia","HPO_Name__c":"Ataxia","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:613839","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"An elevated level of the enzyme lactate dehydrogenase in the blood circulation.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0025435","HPO_Synonym__c":"Increased circulating LDH concentration; Increased lactate dehydrogenase level","HPO_Name__c":"Increased circulating lactate dehydrogenase concentration","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"OMIM:613839","Feature__r":{"HPO_Description__c":"Delayed myelination.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0012448","HPO_Name__c":"Delayed myelination","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:613839","Feature__r":{"HPO_Description__c":"A generalized non-motor (absence) seizure is a type of a type of dialeptic seizure that is of electrographically generalized onset. It is a generalized seizure characterized by an interruption of activities, a blank stare, and usually the person will be unresponsive when spoken to. Any ictal motor phenomena are minor in comparison to these non-motor features.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002121","HPO_Synonym__c":"Absence seizure; Absence seizures; Brief seizures with staring spells; Petit mal; Petit mal seizure; Petit mal seizures","HPO_Name__c":"Generalized non-motor (absence) seizure","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:613839","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"}},{"Provided_By__c":"OMIM:613839","Feature__r":{"HPO_Description__c":"Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001252","HPO_Synonym__c":"Low muscle tone; Low or weak muscle tone; Muscle hypotonia; Muscular hypotonia","HPO_Name__c":"Hypotonia","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:613839","Feature__r":{"HPO_Description__c":"Marked, involuntary jerking of the eyelids.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0025097","HPO_Synonym__c":"Blepharoclonus","HPO_Name__c":"Eyelid myoclonus","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:613839","Feature__r":{"HPO_Description__c":"An abnormal reduction in numbers of all blood cell types (red blood cells, white blood cells, and platelets).","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001876","HPO_Synonym__c":"Low blood cell count","HPO_Name__c":"Pancytopenia","Feature_System__c":"Blood and Blood-Forming Tissue","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:613839","Feature__r":{"HPO_Description__c":"Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002059","HPO_Synonym__c":"Degeneration of cerebrum","HPO_Name__c":"Cerebral atrophy","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:613839","Feature__r":{"HPO_Description__c":"Generalized muscular hypotonia (abnormally low muscle tone).","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001290","HPO_Synonym__c":"Generalized decreased muscle tone; Generalized muscular hypotonia; Hypotonia, generalized","HPO_Name__c":"Generalized hypotonia","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:613839","Feature__r":{"HPO_Description__c":"Cerebellar hypoplasia is a descriptive term implying a cerebellum with a reduced volume, but a normal shape and is stable over time.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001321","HPO_Synonym__c":"Congenital cerebellar hypoplasia; Hypoplasia of cerebellum; Hypoplastic cerebellum; Small cerebellum; Underdeveloped cerebellum","HPO_Name__c":"Cerebellar hypoplasia","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:613839","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"A reduced concentration of 5-methyltetrahydrofolate(2-) in the cerebrospinal fluid (CSF). 5-methyltetrahydrofolate is the active folate metabolite.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0012446","HPO_Synonym__c":"Low CSF 5-methyltetrahydrofolate; Reduced CSF 5-methyltetrahydrofolate concentration","HPO_Name__c":"Decreased CSF 5-methyltetrahydrofolate concentration","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"OMIM:613839","Feature__r":{"HPO_Description__c":"Head circumference which falls below 2 standard deviations below the mean for age and sex because of insufficient head growth after birth.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0005484","HPO_Synonym__c":"Acquired microcephaly; Deceleration of head growth; Microcephaly, acquired; Microcephaly, postnatal; Postnatal deceleration of head circumference; Postnatal microcephaly","HPO_Name__c":"Secondary microcephaly","Feature_System__c":"Nervous System; Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}}],"tags":{"Cause":["Genetics","Inborn Errors of Metabolism"],"Disease Category":["Genetics","Neurology","Hematology","Inborn Errors of Metabolism"],"Specialist":["Genetics","Neurology","Hematology","Epilepsy","Pediatrics"],"Account":["Epilepsy"]},"synonyms":["dhfr deficiency"," dihydrofolate reductase deficiency"," megaloblastic anemia due to dihydrofolate reductase deficiency"]}