{"frequencyBands":{"HP:0040280":[100,100],"HP:0040281":[80,99],"HP:0040282":[30,79],"HP:0040283":[5,29],"HP:0040284":[1,4],"HP:0040285":[0,0]},"page":{"columns":[{"gene":"","key":"MONDO:0013971/OMIM:614924","label":"Combined oxidative phosphorylation deficiency 12","mondoId":"MONDO:0013971","onsetQualifier":null,"recordKeys":["01fdfffebd922d857ec64de1a03b89a2128f52358faa6c9df5348542969b4105","0e452d625003cecaab396dc2d9dff1ff656a256450d9f60781738c030ad2e1bf","128af7329067ea1bb6802acc365f3727ca0b43a2a0b1b40054311b198ffbe504","16f4db6f6c3f75d3989331f21af2cdd90da8565e1692ba8f8d3bb8060ec6aff9","1a45b49c1193a91a462c6e30c8b685d1ba99d04b49296a17eb0a670bf5b47fee","1dd06c5d2e3dd228a1a93be332e1404ad147af061740638e47624f4840a68e0e","2e9727f932c241ba919ec954e59e475b4b53e9fafa2f3ee76633707aee4f9608","3b9ce711638457b1bfb56e46a1efaf2f1a7d8d9044a563889ee6ac72a99edf66","461d7d2ea2b123e0336dc76b33d922e7930a41abc803d2f48176ae25deebcc0d","4b94fe32411dbddcc80637d8acfc5217e8390f1fe06bead5e6e456b83df2c32f","728620eb965d672e0e8da52b0db40fb296841c7361fe7559bcf5a8adf5debcfe","807352bf5eb8d7cee69ddad1221a28d6cbf3feb94698c265168c76f8bb919ead","828f225777043b0b7f79411fe492240821a49cc162e8245e83ad854fbd491d3c","905c17fbd931f295206e32ad5238dcce44e360646c2be6807a25d5dcd1ce0350","92f10bc522781248feb21226a88a747166d55aac4feab22feb8e6fa919317e27","962286e643abc6dd9e8383bbf556928eaa2cb8fec54445a1fb57fdcbc68d02f2","a8bfbeb2dc9710004dcd471437ea7d4b3e312173d53a3545f5e8d2f702a82aea","ab633d95bdefc6af9398918b991cfbc68bf947ad9cbb9e42c4f295f6f0110c75","acecc5fcfa1c57d52aa875528cd255bf7e19c3466aeeff77af978cee78a6cb2a","ad571403614b0bd129295a4e2844c55a9036238e31be46d71a1cd020bb9f56a4","b1bf890b903ff581142bd64f93f6e4ac01c98a6be68eb075a3bc3c059f0d75a7","b3ac653f38c8819390146638e50101f046b4bb2d09a9370916ff1c550b167f2a","b807030cd35e07c390d642ec2b46ab827e61794d7fd77fc703f8f71f8cd7dba9","b85bd4e2bed751d3b2444baee0184169e0648016c01fe07eb9b354f0b0b5c5ef","b977eac0274c06e7a7400aeb57d942c486fd9396178c6d5ba6bf19f69edf97b4","c3675713df81b6b52e1128b26ac78d597c5f402db2dc00e205f7f8273ce526ec","c3c4366545c6f3c2f6858708c2614cb0d28179d1ff382db03692dc7dd971ef95","c58639f3edf31baded1b3da2614ddd80b17fdb2104214fd8eddc4b124d1dd2f6","c88f383379b153814159979d844b736762989faafac057516cc679447ec46360","d67b11413f6287844a8db9c910aa94892a5bf7fccebb1b964119f765d6a36088","e1a20266e009239f6e8995bc26efe23ea8d6736d236f710a0b09affbd5767469","e5f6e3dcaed5e2b73849088cd183ddf40ea9862855900416926927ac3b9a0b57","ebfe1c6ef2c8d6502907c3f0029c33bed735c8f2bf9521cd4b53c8fea2741f98","f48cbe665b5eb4d00a3909b00336be5e1f89ae35196aad991be112d8ff13c270","f950dd907b247a9fa3740503a3fa279cd76e707b823f9249ba30f2fc105ef619"],"recordQualifiers":{},"scopeLabel":"OMIM:614924","sourceIds":["OMIM:614924"],"sourceScope":"This column retains the native source entry. It is not a pooled estimate for the umbrella condition."}],"comparison":{"collapseColumnsLabel":"Show initial comparisons","defaultColumnKeys":["MONDO:0013971/OMIM:614924"],"expandColumnsLabel":"Compare all source entries","intro":"Compare the original source entries. Different entries may describe different patient groups.","primaryFeatureIds":[],"scopeNoteHtml":"<p>Each column keeps its native condition scope. Initial features are displayed alphabetically, not ranked by clinical importance. Counts remain separate, and an empty cell does not mean a feature cannot occur.</p>"},"coverage":{"countRecords":20,"emptyColumnKeys":[],"hpoRelease":"2026-06-23","narrativeSourceChanges":[],"records":35,"sourceGroups":{"omim":14,"orphanet":0,"published":21}},"features":[{"hpoId":"HP:0001344","label":"Absent speech","primary":false},{"hpoId":"HP:0001274","label":"Agenesis of corpus callosum","primary":false},{"hpoId":"HP:0008936","label":"Axial hypotonia","primary":false},{"hpoId":"HP:0003487","label":"Babinski sign","primary":false},{"hpoId":"HP:0002067","label":"Slowness of movement","primary":false},{"hpoId":"HP:0001396","label":"Cholestasis","primary":false},{"hpoId":"HP:0000175","label":"Cleft palate","primary":false},{"hpoId":"HP:0011923","label":"Decreased activity of mitochondrial complex I","primary":false},{"hpoId":"HP:0011924","label":"Decreased activity of mitochondrial complex III","primary":false},{"hpoId":"HP:0008347","label":"Decreased activity of mitochondrial complex IV","primary":false},{"hpoId":"HP:0002188","label":"Delayed CNS myelination","primary":false},{"hpoId":"HP:0002376","label":"Developmental regression","primary":false},{"hpoId":"HP:0006989","label":"Dysplastic corpus callosum","primary":false},{"hpoId":"HP:0001332","label":"Dystonia","primary":false},{"hpoId":"HP:0031964","label":"Elevated circulating alanine aminotransferase concentration","primary":false},{"hpoId":"HP:0006254","label":"Elevated circulating alpha-fetoprotein concentration","primary":false},{"hpoId":"HP:0031956","label":"Elevated circulating aspartate aminotransferase concentration","primary":false},{"hpoId":"HP:0001508","label":"Failure to thrive","primary":false},{"hpoId":"HP:0011968","label":"Feeding difficulties","primary":false},{"hpoId":"HP:0001263","label":"Global developmental delay","primary":false},{"hpoId":"HP:0002240","label":"Hepatomegaly","primary":false},{"hpoId":"HP:0002079","label":"Hypoplasia of the corpus callosum","primary":false},{"hpoId":"HP:0001252","label":"Hypotonia","primary":false},{"hpoId":"HP:0002151","label":"Increased circulating lactate concentration","primary":false},{"hpoId":"HP:0003128","label":"Lactic acidosis","primary":false},{"hpoId":"HP:0002352","label":"Leukoencephalopathy","primary":false},{"hpoId":"HP:0001403","label":"Macrovesicular hepatic steatosis","primary":false},{"hpoId":"HP:0001319","label":"Neonatal hypotonia","primary":false},{"hpoId":"HP:0000602","label":"Ophthalmoplegia","primary":false},{"hpoId":"HP:0002421","label":"Poor head control","primary":false},{"hpoId":"HP:0000508","label":"Ptosis","primary":false},{"hpoId":"HP:0003200","label":"Ragged-red muscle fibers","primary":false},{"hpoId":"HP:0001250","label":"Seizures","primary":false},{"hpoId":"HP:0001285","label":"Spastic tetraparesis","primary":false},{"hpoId":"HP:0000505","label":"Visual impairment","primary":false}],"ledeHtml":"Leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL) is a disorder that affects the brain. LTBL is one of a group of genetic disorders called leukodystrophies, which feature abnormalities of the nervous system&#x27;s white matter. White matter consists of nerve fibers covered by a fatty substance, called myelin, that insulates nerve fibers and promotes the rapid transmission of nerve impulses.","mondoId":"MONDO:0013971","records":[{"frequencyKind":"count","key":"01fdfffebd922d857ec64de1a03b89a2128f52358faa6c9df5348542969b4105","raw":{"aspect":"P","body_system":"metabolic","disease_id":"OMIM:614924","disease_name":"Combined oxidative phosphorylation deficiency 12","evidence":"PCS","frequency_raw":"1/1","hpo_id":"HP:0003128","is_excluded":false,"label":"Lactic acidosis","onset_id":null,"reference":"PMID:22492562","source_release":"2026-06-23"},"sourceGroups":["published"]},{"frequencyKind":"reported","key":"0e452d625003cecaab396dc2d9dff1ff656a256450d9f60781738c030ad2e1bf","raw":{"aspect":"P","body_system":"nervous_system","disease_id":"OMIM:614924","disease_name":"Combined oxidative phosphorylation deficiency 12","evidence":"TAS","frequency_raw":null,"hpo_id":"HP:0001332","is_excluded":false,"label":"Dystonia","onset_id":null,"reference":"OMIM:614924","source_release":"2026-06-23"},"sourceGroups":["omim"]},{"frequencyKind":"reported","key":"128af7329067ea1bb6802acc365f3727ca0b43a2a0b1b40054311b198ffbe504","raw":{"aspect":"P","body_system":"growth","disease_id":"OMIM:614924","disease_name":"Combined oxidative phosphorylation deficiency 12","evidence":"TAS","frequency_raw":null,"hpo_id":"HP:0001508","is_excluded":false,"label":"Failure to thrive","onset_id":null,"reference":"OMIM:614924","source_release":"2026-06-23"},"sourceGroups":["omim"]},{"frequencyKind":"range","key":"16f4db6f6c3f75d3989331f21af2cdd90da8565e1692ba8f8d3bb8060ec6aff9","raw":{"aspect":"P","body_system":"head_and_neck","disease_id":"OMIM:614924","disease_name":"Combined oxidative phosphorylation deficiency 12","evidence":"TAS","frequency_raw":"HP:0040283","hpo_id":"HP:0000175","is_excluded":false,"label":"Cleft palate","onset_id":null,"reference":"OMIM:614924","source_release":"2026-06-23"},"sourceGroups":["omim"]},{"frequencyKind":"count","key":"1a45b49c1193a91a462c6e30c8b685d1ba99d04b49296a17eb0a670bf5b47fee","raw":{"aspect":"P","body_system":"nervous_system","disease_id":"OMIM:614924","disease_name":"Combined oxidative phosphorylation deficiency 12","evidence":"PCS","frequency_raw":"7/8","hpo_id":"HP:0002188","is_excluded":false,"label":"Delayed CNS myelination","onset_id":null,"reference":"PMID:22492562","source_release":"2026-06-23"},"sourceGroups":["published"]},{"frequencyKind":"count","key":"1dd06c5d2e3dd228a1a93be332e1404ad147af061740638e47624f4840a68e0e","raw":{"aspect":"P","body_system":"nervous_system","disease_id":"OMIM:614924","disease_name":"Combined oxidative phosphorylation deficiency 12","evidence":"PCS","frequency_raw":"10/12","hpo_id":"HP:0002376","is_excluded":false,"label":"Developmental regression","onset_id":null,"reference":"PMID:22492562","source_release":"2026-06-23"},"sourceGroups":["published"]},{"frequencyKind":"count","key":"2e9727f932c241ba919ec954e59e475b4b53e9fafa2f3ee76633707aee4f9608","raw":{"aspect":"P","body_system":"metabolic","disease_id":"OMIM:614924","disease_name":"Combined oxidative phosphorylation deficiency 12","evidence":"PCS","frequency_raw":"1/1","hpo_id":"HP:0008347","is_excluded":false,"label":"Decreased activity of mitochondrial complex IV","onset_id":null,"reference":"PMID:22492562","source_release":"2026-06-23"},"sourceGroups":["published"]},{"frequencyKind":"count","key":"3b9ce711638457b1bfb56e46a1efaf2f1a7d8d9044a563889ee6ac72a99edf66","raw":{"aspect":"P","body_system":"metabolic","disease_id":"OMIM:614924","disease_name":"Combined oxidative phosphorylation deficiency 12","evidence":"PCS","frequency_raw":"1/1","hpo_id":"HP:0011924","is_excluded":false,"label":"Decreased activity of mitochondrial complex III","onset_id":null,"reference":"PMID:22492562","source_release":"2026-06-23"},"sourceGroups":["published"]},{"frequencyKind":"count","key":"461d7d2ea2b123e0336dc76b33d922e7930a41abc803d2f48176ae25deebcc0d","raw":{"aspect":"P","body_system":"metabolic","disease_id":"OMIM:614924","disease_name":"Combined oxidative phosphorylation deficiency 12","evidence":"PCS","frequency_raw":"1/1","hpo_id":"HP:0031956","is_excluded":false,"label":"Elevated circulating aspartate aminotransferase concentration","onset_id":null,"reference":"PMID:22492562","source_release":"2026-06-23"},"sourceGroups":["published"]},{"frequencyKind":"count","key":"4b94fe32411dbddcc80637d8acfc5217e8390f1fe06bead5e6e456b83df2c32f","raw":{"aspect":"P","body_system":"nervous_system","disease_id":"OMIM:614924","disease_name":"Combined oxidative phosphorylation deficiency 12","evidence":"PCS","frequency_raw":"6/11","hpo_id":"HP:0002079","is_excluded":false,"label":"Hypoplasia of the corpus callosum","onset_id":null,"reference":"PMID:22492562","source_release":"2026-06-23"},"sourceGroups":["published"]},{"frequencyKind":"reported","key":"728620eb965d672e0e8da52b0db40fb296841c7361fe7559bcf5a8adf5debcfe","raw":{"aspect":"P","body_system":"nervous_system","disease_id":"OMIM:614924","disease_name":"Combined oxidative phosphorylation deficiency 12","evidence":"TAS","frequency_raw":null,"hpo_id":"HP:0006989","is_excluded":false,"label":"Dysplastic corpus callosum","onset_id":null,"reference":"OMIM:614924","source_release":"2026-06-23"},"sourceGroups":["omim"]},{"frequencyKind":"reported","key":"807352bf5eb8d7cee69ddad1221a28d6cbf3feb94698c265168c76f8bb919ead","raw":{"aspect":"P","body_system":"musculoskeletal","disease_id":"OMIM:614924","disease_name":"Combined oxidative phosphorylation deficiency 12","evidence":"TAS","frequency_raw":null,"hpo_id":"HP:0003200","is_excluded":false,"label":"Ragged-red muscle fibers","onset_id":null,"reference":"OMIM:614924","source_release":"2026-06-23"},"sourceGroups":["omim"]},{"frequencyKind":"count","key":"828f225777043b0b7f79411fe492240821a49cc162e8245e83ad854fbd491d3c","raw":{"aspect":"P","body_system":"metabolic","disease_id":"OMIM:614924","disease_name":"Combined oxidative phosphorylation deficiency 12","evidence":"PCS","frequency_raw":"1/1","hpo_id":"HP:0011923","is_excluded":false,"label":"Decreased activity of mitochondrial complex I","onset_id":null,"reference":"PMID:22492562","source_release":"2026-06-23"},"sourceGroups":["published"]},{"frequencyKind":"count","key":"905c17fbd931f295206e32ad5238dcce44e360646c2be6807a25d5dcd1ce0350","raw":{"aspect":"P","body_system":"nervous_system","disease_id":"OMIM:614924","disease_name":"Combined oxidative phosphorylation deficiency 12","evidence":"PCS","frequency_raw":"7/12","hpo_id":"HP:0001344","is_excluded":false,"label":"Absent speech","onset_id":null,"reference":"PMID:22492562","source_release":"2026-06-23"},"sourceGroups":["published"]},{"frequencyKind":"count","key":"92f10bc522781248feb21226a88a747166d55aac4feab22feb8e6fa919317e27","raw":{"aspect":"P","body_system":"musculoskeletal","disease_id":"OMIM:614924","disease_name":"Combined oxidative phosphorylation deficiency 12","evidence":"PCS","frequency_raw":"5/12","hpo_id":"HP:0008936","is_excluded":false,"label":"Axial hypotonia","onset_id":null,"reference":"PMID:22492562","source_release":"2026-06-23"},"sourceGroups":["published"]},{"frequencyKind":"count","key":"962286e643abc6dd9e8383bbf556928eaa2cb8fec54445a1fb57fdcbc68d02f2","raw":{"aspect":"P","body_system":"nervous_system","disease_id":"OMIM:614924","disease_name":"Combined oxidative phosphorylation deficiency 12","evidence":"PCS","frequency_raw":"10/11","hpo_id":"HP:0001263","is_excluded":false,"label":"Global developmental delay","onset_id":null,"reference":"PMID:22492562","source_release":"2026-06-23"},"sourceGroups":["published"]},{"frequencyKind":"reported","key":"a8bfbeb2dc9710004dcd471437ea7d4b3e312173d53a3545f5e8d2f702a82aea","raw":{"aspect":"P","body_system":"musculoskeletal","disease_id":"OMIM:614924","disease_name":"Combined oxidative phosphorylation deficiency 12","evidence":"TAS","frequency_raw":null,"hpo_id":"HP:0001319","is_excluded":false,"label":"Neonatal hypotonia","onset_id":null,"reference":"OMIM:614924","source_release":"2026-06-23"},"sourceGroups":["omim"]},{"frequencyKind":"count","key":"ab633d95bdefc6af9398918b991cfbc68bf947ad9cbb9e42c4f295f6f0110c75","raw":{"aspect":"P","body_system":"musculoskeletal","disease_id":"OMIM:614924","disease_name":"Combined oxidative phosphorylation deficiency 12","evidence":"PCS","frequency_raw":"1/1","hpo_id":"HP:0002421","is_excluded":false,"label":"Poor head control","onset_id":null,"reference":"PMID:22492562","source_release":"2026-06-23"},"sourceGroups":["published"]},{"frequencyKind":"reported","key":"acecc5fcfa1c57d52aa875528cd255bf7e19c3466aeeff77af978cee78a6cb2a","raw":{"aspect":"P","body_system":"eye","disease_id":"OMIM:614924","disease_name":"Combined oxidative phosphorylation deficiency 12","evidence":"TAS","frequency_raw":null,"hpo_id":"HP:0000505","is_excluded":false,"label":"Visual impairment","onset_id":null,"reference":"OMIM:614924","source_release":"2026-06-23"},"sourceGroups":["omim"]},{"frequencyKind":"reported","key":"ad571403614b0bd129295a4e2844c55a9036238e31be46d71a1cd020bb9f56a4","raw":{"aspect":"P","body_system":"eye","disease_id":"OMIM:614924","disease_name":"Combined oxidative phosphorylation deficiency 12","evidence":"TAS","frequency_raw":null,"hpo_id":"HP:0000508","is_excluded":false,"label":"Ptosis","onset_id":null,"reference":"OMIM:614924","source_release":"2026-06-23"},"sourceGroups":["omim"]},{"frequencyKind":"reported","key":"b1bf890b903ff581142bd64f93f6e4ac01c98a6be68eb075a3bc3c059f0d75a7","raw":{"aspect":"P","body_system":"nervous_system","disease_id":"OMIM:614924","disease_name":"Combined oxidative phosphorylation deficiency 12","evidence":"PCS","frequency_raw":null,"hpo_id":"HP:0002352","is_excluded":false,"label":"Leukoencephalopathy","onset_id":null,"reference":"PMID:22492562","source_release":"2026-06-23"},"sourceGroups":["published"]},{"frequencyKind":"count","key":"b3ac653f38c8819390146638e50101f046b4bb2d09a9370916ff1c550b167f2a","raw":{"aspect":"P","body_system":"nervous_system","disease_id":"OMIM:614924","disease_name":"Combined oxidative phosphorylation deficiency 12","evidence":"PCS","frequency_raw":"4/12","hpo_id":"HP:0003487","is_excluded":false,"label":"Babinski sign","onset_id":null,"reference":"PMID:22492562","source_release":"2026-06-23"},"sourceGroups":["published"]},{"frequencyKind":"count","key":"b807030cd35e07c390d642ec2b46ab827e61794d7fd77fc703f8f71f8cd7dba9","raw":{"aspect":"P","body_system":"metabolic","disease_id":"OMIM:614924","disease_name":"Combined oxidative phosphorylation deficiency 12","evidence":"PCS","frequency_raw":"1/1","hpo_id":"HP:0006254","is_excluded":false,"label":"Elevated circulating alpha-fetoprotein concentration","onset_id":null,"reference":"PMID:22492562","source_release":"2026-06-23"},"sourceGroups":["published"]},{"frequencyKind":"reported","key":"b85bd4e2bed751d3b2444baee0184169e0648016c01fe07eb9b354f0b0b5c5ef","raw":{"aspect":"P","body_system":"eye","disease_id":"OMIM:614924","disease_name":"Combined oxidative phosphorylation deficiency 12","evidence":"TAS","frequency_raw":null,"hpo_id":"HP:0000602","is_excluded":false,"label":"Ophthalmoplegia","onset_id":null,"reference":"OMIM:614924","source_release":"2026-06-23"},"sourceGroups":["omim"]},{"frequencyKind":"count","key":"b977eac0274c06e7a7400aeb57d942c486fd9396178c6d5ba6bf19f69edf97b4","raw":{"aspect":"P","body_system":"metabolic","disease_id":"OMIM:614924","disease_name":"Combined oxidative phosphorylation deficiency 12","evidence":"PCS","frequency_raw":"1/1","hpo_id":"HP:0031964","is_excluded":false,"label":"Elevated circulating alanine aminotransferase concentration","onset_id":null,"reference":"PMID:22492562","source_release":"2026-06-23"},"sourceGroups":["published"]},{"frequencyKind":"count","key":"c3675713df81b6b52e1128b26ac78d597c5f402db2dc00e205f7f8273ce526ec","raw":{"aspect":"P","body_system":"nervous_system","disease_id":"OMIM:614924","disease_name":"Combined oxidative phosphorylation deficiency 12","evidence":"PCS","frequency_raw":"6/12","hpo_id":"HP:0001250","is_excluded":false,"label":"Seizure","onset_id":null,"reference":"PMID:22492562","source_release":"2026-06-23"},"sourceGroups":["published"]},{"frequencyKind":"range","key":"c3c4366545c6f3c2f6858708c2614cb0d28179d1ff382db03692dc7dd971ef95","raw":{"aspect":"P","body_system":"digestive","disease_id":"OMIM:614924","disease_name":"Combined oxidative phosphorylation deficiency 12","evidence":"TAS","frequency_raw":"HP:0040283","hpo_id":"HP:0001396","is_excluded":false,"label":"Cholestasis","onset_id":null,"reference":"OMIM:614924","source_release":"2026-06-23"},"sourceGroups":["omim"]},{"frequencyKind":"count","key":"c58639f3edf31baded1b3da2614ddd80b17fdb2104214fd8eddc4b124d1dd2f6","raw":{"aspect":"P","body_system":"nervous_system","disease_id":"OMIM:614924","disease_name":"Combined oxidative phosphorylation deficiency 12","evidence":"PCS","frequency_raw":"9/12","hpo_id":"HP:0001285","is_excluded":false,"label":"Spastic tetraparesis","onset_id":null,"reference":"PMID:22492562","source_release":"2026-06-23"},"sourceGroups":["published"]},{"frequencyKind":"range","key":"c88f383379b153814159979d844b736762989faafac057516cc679447ec46360","raw":{"aspect":"P","body_system":"digestive","disease_id":"OMIM:614924","disease_name":"Combined oxidative phosphorylation deficiency 12","evidence":"TAS","frequency_raw":"HP:0040283","hpo_id":"HP:0002240","is_excluded":false,"label":"Hepatomegaly","onset_id":null,"reference":"OMIM:614924","source_release":"2026-06-23"},"sourceGroups":["omim"]},{"frequencyKind":"count","key":"d67b11413f6287844a8db9c910aa94892a5bf7fccebb1b964119f765d6a36088","raw":{"aspect":"P","body_system":"digestive","disease_id":"OMIM:614924","disease_name":"Combined oxidative phosphorylation deficiency 12","evidence":"PCS","frequency_raw":"3/12","hpo_id":"HP:0011968","is_excluded":false,"label":"Feeding difficulties","onset_id":null,"reference":"PMID:22492562","source_release":"2026-06-23"},"sourceGroups":["published"]},{"frequencyKind":"range","key":"e1a20266e009239f6e8995bc26efe23ea8d6736d236f710a0b09affbd5767469","raw":{"aspect":"P","body_system":"metabolic","disease_id":"OMIM:614924","disease_name":"Combined oxidative phosphorylation deficiency 12","evidence":"TAS","frequency_raw":"HP:0040283","hpo_id":"HP:0001403","is_excluded":false,"label":"Macrovesicular hepatic steatosis","onset_id":null,"reference":"OMIM:614924","source_release":"2026-06-23"},"sourceGroups":["omim"]},{"frequencyKind":"reported","key":"e5f6e3dcaed5e2b73849088cd183ddf40ea9862855900416926927ac3b9a0b57","raw":{"aspect":"P","body_system":"metabolic","disease_id":"OMIM:614924","disease_name":"Combined oxidative phosphorylation deficiency 12","evidence":"TAS","frequency_raw":null,"hpo_id":"HP:0002151","is_excluded":false,"label":"Increased circulating lactate concentration","onset_id":null,"reference":"OMIM:614924","source_release":"2026-06-23"},"sourceGroups":["omim"]},{"frequencyKind":"reported","key":"ebfe1c6ef2c8d6502907c3f0029c33bed735c8f2bf9521cd4b53c8fea2741f98","raw":{"aspect":"P","body_system":"nervous_system","disease_id":"OMIM:614924","disease_name":"Combined oxidative phosphorylation deficiency 12","evidence":"TAS","frequency_raw":null,"hpo_id":"HP:0002067","is_excluded":false,"label":"Bradykinesia","onset_id":null,"reference":"OMIM:614924","source_release":"2026-06-23"},"sourceGroups":["omim"]},{"frequencyKind":"count","key":"f48cbe665b5eb4d00a3909b00336be5e1f89ae35196aad991be112d8ff13c270","raw":{"aspect":"P","body_system":"musculoskeletal","disease_id":"OMIM:614924","disease_name":"Combined oxidative phosphorylation deficiency 12","evidence":"PCS","frequency_raw":"1/1","hpo_id":"HP:0001252","is_excluded":false,"label":"Hypotonia","onset_id":null,"reference":"PMID:22492562","source_release":"2026-06-23"},"sourceGroups":["published"]},{"frequencyKind":"count","key":"f950dd907b247a9fa3740503a3fa279cd76e707b823f9249ba30f2fc105ef619","raw":{"aspect":"P","body_system":"nervous_system","disease_id":"OMIM:614924","disease_name":"Combined oxidative phosphorylation deficiency 12","evidence":"PCS","frequency_raw":"3/11","hpo_id":"HP:0001274","is_excluded":false,"label":"Agenesis of corpus callosum","onset_id":null,"reference":"PMID:22492562","source_release":"2026-06-23"},"sourceGroups":["published"]}],"referenceLabels":{},"references":{"causeHtml":"<ul><li><a href=\"https://medlineplus.gov/genetics/condition/leukoencephalopathy-with-thalamus-and-brainstem-involvement-and-high-lactate\">Leukoencephalopathy with thalamus and brainstem involvement and high lactate</a></li></ul>","identityNote":"MONDO cross-references identify native condition entries. Ancestor membership does not transfer phenotype values between groups.","importantHtml":""},"sections":[{"bodyHtml":"<p>LTBL is caused by mutations in the EARS2 gene, which provides instructions for making an enzyme called mitochondrial glutamyl-tRNA synthetase. This enzyme is important in the production (synthesis) of proteins in cellular structures called mitochondria, the energy-producing centers in cells. While most protein synthesis occurs in the fluid surrounding the cell nucleus (cytoplasm), some proteins are synthesized in the mitochondria.</p><p>During protein synthesis, in either the mitochondria or the cytoplasm, building blocks called amino acids are connected together in a specific order, creating a chain of amino acids that forms the protein. Mitochondrial glutamyl-tRNA synthetase plays a role in adding the amino acid glutamate at the proper place in mitochondrial proteins.</p><p>Mutations in the EARS2 gene likely reduce the amount of mitochondrial aspartyl-tRNA synthetase protein, which hinders the addition of glutamate to mitochondrial proteins. Researchers speculate that impaired protein assembly disrupts mitochondrial energy production. However, it is unclear how a reduction of mitochondrial aspartyl-tRNA synthetase specifically affects certain brain regions, causing LTBL.</p><p class=\"section-source\"><a href=\"https://medlineplus.gov/genetics/condition/leukoencephalopathy-with-thalamus-and-brainstem-involvement-and-high-lactate/#causes\">MedlinePlus Genetics: Causes</a></p>","key":"forms","title":"What causes Leukoencephalopathy with thalamus and brainstem involvement and high lactate?"},{"bodyHtml":"<p>LTBL is characterized by distinct changes in the brain, which can be seen using magnetic resonance imaging (MRI). These abnormalities typically involve white matter in regions of the brain known as the cerebrum and cerebellum. Abnormalities can also be seen in other regions of the brain, including the brainstem, which is the part that connects to the spinal cord. Affected brain regions include the thalamus, midbrain, pons, and medulla oblongata. Thinning of the tissue that connects the left and right halves of the brain (the corpus callosum) also occurs in people with LTBL. In addition, most affected individuals have a high level of a substance called lactate in the brain and elsewhere in the body.</p><p>The severity of the condition varies. Mildly affected individuals usually develop signs and symptoms after the age of 6 months. Loss of mental and movement abilities (psychomotor regression), muscle stiffness (spasticity), and extreme irritability are common, and some people with mild LTBL develop seizures. However, after age 2, the signs and symptoms of the condition improve: affected children regain some psychomotor abilities, seizures are reduced or disappear, MRI results become more normal, and lactate levels drop.</p><p>Severely affected individuals have features that begin soon after birth. These infants typically have delayed development of mental and movement abilities (psychomotor delay), weak muscle tone (hypotonia), involuntary muscle tensing (dystonia), muscle spasticity, and seizures. Some have extremely high levels of lactate (lactic acidosis), which can cause serious breathing problems and an abnormal heartbeat. Liver failure occurs in some severely affected infants. In severe cases, the signs and symptoms do not improve and can be life-threatening. In some people with LTBL, the features fall between mild and severe.</p><p class=\"section-source\">Source: <a href=\"https://medlineplus.gov/genetics/condition/leukoencephalopathy-with-thalamus-and-brainstem-involvement-and-high-lactate\">MedlinePlus Genetics</a></p>","key":"overview","title":"Condition overview"}],"sharedSources":[],"slug":"leukoencephalopathy-with-thalamus-and-brainstem-involvement-and-high-lactate","sourceDocuments":[{"name":"Leukoencephalopathy with thalamus and brainstem involvement and high lactate","reviewed":"2016-09","sections":{"causes":{"fetchedAt":"2026-10-20T20:22:55.409291+00:00","label":"Causes","pageSha256":"bc69968f83612f502e5b71cffcb04c8ebd49f38c3e71f4b008574ebf300378c1","sourceUrl":"https://medlineplus.gov/genetics/condition/leukoencephalopathy-with-thalamus-and-brainstem-involvement-and-high-lactate/#causes","status":"available"}},"source_release":"2026-10-01","url":"https://medlineplus.gov/genetics/condition/leukoencephalopathy-with-thalamus-and-brainstem-involvement-and-high-lactate"}],"sourceNote":"MedlinePlus descriptions and Causes; original HPO annotations.","takeawayHtml":"Cause explanations are from MedlinePlus Genetics. Feature values below retain their original sources and patient groups.","title":"Leukoencephalopathy with thalamus and brainstem involvement and high lactate"},"schemaVersion":1}