{"Name":"Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins","DiseaseID__c":"GARD:0010593","id":10593,"encodedName":"acute-infantile-liver-failure-due-to-synthesis-defect-of-mtdna-encoded-proteins","IsDeleted":false,"Disease_Name_Full__c":"Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins","Xref_IDs__c":"C3278664; DOID:0080778; MEDGEN:480294; MONDO:0013111; OMIM:613070; ORPHA:217371","USA_Estimate__c":"1,000","No_of_Specialist_Tagsa__c":3,"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":4,"Disease_Characteristics_Score__c":7,"No_of_Age_at_Onset__c":2,"Description_Source__c":"MONDO:0013111","Disease_Description__c":"A rare mitochondrial respiratory chain deficiency due to TRMU deficiency leading to mitochondrial tRNA synthesis defect and characterized clinically by transient, but life-threatening acute liver failure episodes.","GARD_Name__c":"Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins","GARD_Synonym__c":"acute infantile liver failure due to synthesis defect of mitochondrial dna-encoded proteins; infantile liver failure caused by mutation in trmu; lfit; liver failure acute infantile; liver failure, infantile, transient; liver failure, transient infantile; transient infantile liver failure; trmu deficiency; trmu infantile liver failure","Curated_Disease_Description_Source__c":"MEDGEN:C3278664","Curated_Disease_Description__c":"Acute infantile liver failure resulting from TRMU mutation is a transient disorder of hepatic function. In addition to elevated liver enzymes, jaundice, vomiting, coagulopathy, and hyperbilirubinemia, the presence of increased serum lactate is consistent with a defect in mitochondrial respiratory function. With supportive care, patients who survive the initial acute episode can recover and show normal development (Zeharia et al., 2009).See also transient infantile mitochondrial myopathy (MMIT; 500009), which is a similar disorder.A more severe, permanent disorder with some overlapping features is associated with mitochondrial DNA depletion (251880).See ILFS1 (615438) for information on syndromic infantile liver failure.","Curated_USA_Estimate_Source__c":null,"Curated_USA_Estimate__c":"1,000","Age_at_Onset_Snippet_Text__c":"as a Newborn and as an Infant","SourceID__c":"ORPHA:217371","Deprecated__c":"No","Disease_Concept_Type__c":"Rare Disease Entity","MONDO_ID__c":"MONDO:0013111","ORPHANET_ID__c":"ORPHA:217371","Replaced_By_ID__c":null,"Display_Spanish_Disease_Name__c":"Insuficiencia hepática infantil aguda por un defecto de síntesis de las proteínas codificadas por el adnmt","Spanish_Description_Source__c":"ORPHA:217371","Spanish_Description__c":"Es una deficiencia poco frecuente de la cadena respiratoria mitocondrial debida al déficit de TRMU, que conduce a un defecto en la síntesis de ARNt mitocondrial y que está caracterizada clínicamente por episodios de insuficiencia hepática aguda, transitorios pero potencialmente mortales.","Spanish_Disease_Name__c":"insuficiencia hepática infantil aguda por un defecto de síntesis de las proteínas codificadas por el adnmt","Spanish_GARD_Synonym__c":"fallo hepático infantil agudo por un defecto de síntesis de las proteínas codificadas por el adn mitocondrial; fallo hepático infantil agudo por un defecto de síntesis de las proteínas codificadas por el adnm; insuficiencia hepática infantil aguda por un defecto de síntesis de las proteínas codificadas por el adn mitocondrial","Category_Linearization__c":"ORPHA:57146","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":"Acute infantile liver failure resulting from TRMU mutation is a transient disorder of hepatic function. In addition to elevated liver enzymes, jaundice, vomiting, coagulopathy, and hyperbilirubinemia, the presence of increased serum lactate is consistent with a defect in mitochondrial respiratory function. With supportive care, patients who survive the initial acute episode can recover and show normal development (Zeharia et al., 2009).See also transient infantile mitochondrial myopathy (MMIT; 500009), which is a similar disorder.A more severe, permanent disorder with some overlapping features is associated with mitochondrial DNA depletion (251880).See ILFS1 (615438) for information on syndromic infantile liver failure.","Curated_Disease_Description_Source__c":"MEDGEN:C3278664","GARD_Synonym__c":"acute infantile liver failure due to synthesis defect of mitochondrial dna-encoded proteins; infantile liver failure caused by mutation in trmu; lfit; liver failure acute infantile; liver failure, infantile, transient; liver failure, transient infantile; transient infantile liver failure; trmu deficiency; trmu infantile liver failure","Name":"Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins","Curated_USA_Estimate__c":"1,000","estimateUsa":"1,000"}],"Organization_Supported_Diseases__c":[{"Account_Name__c":"Children's Liver Disease Foundation","Website__c":"https://childliverdisease.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":"Gastroenterology","Tag_Category__c":"Disease Category;Specialist","category_description":"Gastrointestinal diseases, or digestive diseases, affect the esophagus, stomach, small intestine, large intestine, liver, gallbladder, or pancreas.","curated_tag_name":"Gastrointestinal 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":"Mitochondrial","Tag_Category__c":"Account;Cause;Disease Category","category_description":"Mitochondrial diseases are a group of genetic diseases that affect the ability of the body's cells to make energy.","curated_tag_name":"Mitochondrial diseases"},{"Tag_Name__c":"Pediatrics","Tag_Category__c":"Specialist"}],"Age_At_Onset__c":[{"Age_At_Onset__c":"Neonatal","Provided_By__c":"ORPHA:217371"},{"Age_At_Onset__c":"Infancy","Provided_By__c":"ORPHA:217371"}],"Diagnosis__c":[{"Type__c":"GTR","Curie__c":"MEDGEN:C3278664"}],"External_Identifier_Disease__c":[{"URL__c":"https://raresource.nih.gov/diseases/filter/0010593","Source__c":"RareSource"},{"URL__c":"https://www.ncbi.nlm.nih.gov/books/NBK591557","Source__c":"Gene Review","Xref__c":"NBK591557"},{"URL__c":"https://www.orpha.net/en/disease/detail/217371","Source__c":"C3278664; MONDO:0013111","Xref__c":"ORPHA:217371"},{"URL__c":"https://uts.nlm.nih.gov/uts/umls/concept/C3278664","Source__c":"C3278664","Xref__c":"C3278664"},{"URL__c":"https://www.ebi.ac.uk/ols4/ontologies/doid/classes?obo_id=DOID%3A0080778","Source__c":"MONDO:0013111","Xref__c":"DOID:0080778"},{"URL__c":"https://www.omim.org/entry/613070","Source__c":"C3278664; MONDO:0013111; ORPHA:217371","Xref__c":"OMIM:613070"},{"URL__c":"https://www.ncbi.nlm.nih.gov/medgen/?term=480294","Source__c":"C3278664","Xref__c":"MEDGEN:480294"},{"URL__c":"http://purl.obolibrary.org/obo/MONDO_0013111","Source__c":"GARD:0010593","Xref__c":"MONDO:0013111"}],"GARD_Disease_Gene__c":[{"GeneSymbol__c":"TRMU","Gene_Type__c":"protein-coding gene","Causal_Gene__c":true}],"Inheritance__c":["Autosomal recessive"],"GARD_Disease_Feature__c":[{"Provided_By__c":"OMIM:613070","Feature__r":{"HPO_Description__c":"An abnormal buildup of lactic acid in the body, leading to acidification of the blood and other bodily fluids.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0003128","HPO_Synonym__c":"Hyperlacticacidemia; Increased lactate in body; Lactic acidemia; Lacticacidemia; Lacticacidosis","HPO_Name__c":"Lactic acidosis","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"OMIM:613070","HPO_Frequency__c":"Very frequent (80-99%)","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:613070","Feature__r":{"HPO_Description__c":"A form of hepatic steatosis characterized by the presence of small, lipid-laden vesicles in the affected hepatocytes.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001414","HPO_Synonym__c":"Microvesicular steatosis","HPO_Name__c":"Microvesicular hepatic steatosis","Feature_System__c":"Digestive System","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"OMIM:613070","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"An abnormally high concentration in the circulation of alanine aminotransferase (ALT).","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0031964","HPO_Synonym__c":"Alanine aminotransferase increased; Elevated serum alanine aminotransferase; Elevated serum ALT; Elevated serum glutamic-pyruvic transaminase","HPO_Name__c":"Elevated circulating alanine aminotransferase concentration","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"OMIM:613070","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0200125","HPO_Name__c":"Mitochondrial respiratory chain defects","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"OMIM:613070","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"An increased amount of bilirubin in the blood.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002904","HPO_Synonym__c":"High blood bilirubin levels","HPO_Name__c":"Hyperbilirubinemia","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"OMIM:613070","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"The concentration of albumin in the blood circulation is below the lower limit of normal.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0003073","HPO_Synonym__c":"Decreased albumin concentration; Decreased albumin level; Decreased albumin level in blood; Decreased circulating abumin concentration; Hypoalbuminaemia; Hypoalbuminemia; Low blood albumin; Reduced albumin concentration; Reduced albumin level; Reduced albumin level in blood","HPO_Name__c":"Hypoalbuminemia","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"OMIM:613070","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"An abnormally decreased level of immunoglobulin G (IgG) in blood.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0004315","HPO_Synonym__c":"Decreased circulating IgG level; Decreased gamma-globin expression; Decreased IgG level; Decreased IgG level in blood; Decreased immunoglobulin G; Decreased serum IgG; IgG deficiency; Reduced IgG levels","HPO_Name__c":"Decreased circulating IgG concentration","Feature_System__c":"Immune System; Blood and Blood-Forming Tissue","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"OMIM:613070","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Abnormally increased level of blood lactate (2-hydroxypropanoic acid). Lactate is produced from pyruvate by lactate dehydrogenase during normal metabolism. The terms lactate and lactic acid are often used interchangeably but lactate (the component measured in blood) is strictly a weak base whereas lactic acid is the corresponding acid. Lactic acidosis is often used clinically to describe elevated lactate but should be reserved for cases where there is a corresponding acidosis (pH below 7.35).","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002151","HPO_Synonym__c":"Increased blood lactate; Increased serum lactate","HPO_Name__c":"Increased circulating lactate concentration","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"OMIM:613070","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"An increased concentration of dicarboxylic acid in the urine.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0003215","HPO_Synonym__c":"Elevated urinary dicarboxylic acid level","HPO_Name__c":"Dicarboxylic aciduria","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"OMIM:613070","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"A form of hepatic steatosis characterized by the presence of large, lipid-laden vesicles in the affected hepatocytes.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001403","HPO_Synonym__c":"Macrovesicular steatosis","HPO_Name__c":"Macrovesicular hepatic steatosis","Feature_System__c":"Digestive System","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"OMIM:613070","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0008872","HPO_Name__c":"Feeding difficulties in infancy","Feature_System__c":"Digestive System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:613070","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:613070","HPO_Frequency__c":"Very frequent (80-99%)","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:613070","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Distention of the abdomen.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0003270","HPO_Synonym__c":"Abdominal bloating; Abdominal distension; Abdominal swelling; Belly bloating; Bloating; Distended abdomen","HPO_Name__c":"Abdominal distention","Feature_System__c":"Digestive System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:613070","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"An emotional state characterized by negative feelings of heightened frustration, annoyance, or feeling upset, often triggered by internal factors (e.g., fatigue, hunger, unfulfilled desires) or external factors (e.g., social or environmental challenges). Irritability may be unpredictable, and is accompanied by a lowered threshold for emotional reactivity and observable features (speech, facial expressions, or psychomotor activity).","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000737","HPO_Synonym__c":"Cranky; Easily annoyed; Easily bothered; Easily upset; Grumpy; Hot-temper; Irritability; Irritable; Irritable mood; On edge; Quick-temper; Short fuse; Short tempered","HPO_Name__c":"Irritability","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:613070","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"The concentration of 2-hydroxydicarboxylic acid in the urine, normalized for urine concentration, is above the upper limit of normal.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0008160","HPO_Name__c":"3-hydroxydicarboxylic aciduria","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"OMIM:613070","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002013","HPO_Synonym__c":"Emesis; Throwing up; Vomiting","HPO_Name__c":"Vomiting","Feature_System__c":"Digestive System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:613070","Feature__r":{"HPO_Description__c":"Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002910","HPO_Synonym__c":"Abnormal liver enzymes; Abnormal liver function; Abnormal liver function tests; Elevated circulating hepatic transaminase activity; Elevated liver enzymes; Elevated serum transaminases; Elevated transaminases; High liver enzymes; Increased liver enzymes; Increased liver function tests; Increased transaminases; Raised liver enzymes; Subclinical abnormal liver function tests","HPO_Name__c":"Elevated circulating hepatic transaminase concentration","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"OMIM:613070","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Hepatic failure refers to the inability of the liver to perform its normal synthetic and metabolic functions, which can result in coagulopathy and alteration in the mental status of a previously healthy individual. Hepatic failure is defined as acute if there is onset of encephalopathy within 8 weeks of the onset of symptoms in a patient with a previously healthy liver.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0006554","HPO_Synonym__c":"Acute liver failure","HPO_Name__c":"Acute hepatic failure","Feature_System__c":"Digestive System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:613070","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"An increased concentration of lactic acid in the urine.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0003648","HPO_Synonym__c":"High urine lactic acid levels; Increased urine lactate","HPO_Name__c":"Lacticaciduria","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"OMIM:613070","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:613070","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Increased time to coagulation in the prothrombin time test, which is a measure of the extrinsic pathway of coagulation. The results of the prothrombin time test are often expressed in terms of the International normalized ratio (INR), which is calculated as a ratio of the patient's prothrombin time (PT) to a control PT standardized for the potency of the thromboplastin reagent developed by the World Health Organization (WHO) using the formula: INR is equal to Patient PT divided by Control PT.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0008151","HPO_Synonym__c":"Increased INR; Increased international normalized ratio; Low factor II activity; Prolonged PT; Reduced factor II activity; Reduced prothrombin activity","HPO_Name__c":"Prolonged prothrombin time","Feature_System__c":"Blood and Blood-Forming Tissue","HPO_Feature_Type__c":"Symptom"}}],"tags":{"Cause":["Genetics","Inborn Errors of Metabolism","Mitochondrial"],"Disease Category":["Genetics","Gastroenterology","Inborn Errors of Metabolism","Mitochondrial"],"Specialist":["Genetics","Gastroenterology","Pediatrics"],"Account":["Mitochondrial"]},"synonyms":["acute infantile liver failure due to synthesis defect of mitochondrial dna-encoded proteins"," infantile liver failure caused by mutation in trmu"," lfit"," liver failure acute infantile"," liver failure, infantile, transient"," liver failure, transient infantile"," transient infantile liver failure"," trmu deficiency"," trmu infantile liver failure"]}