{"Name":"Multiple mitochondrial dysfunctions syndrome 4","DiseaseID__c":"GARD:0017809","id":17809,"encodedName":"multiple-mitochondrial-dysfunctions-syndrome-4","IsDeleted":false,"Disease_Name_Full__c":"Multiple mitochondrial dysfunctions syndrome 4","Xref_IDs__c":"C4225348; DOID:0080136; MEDGEN:899010; MONDO:0014611; OMIM:616370; ORPHA:457406","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":4,"Disease_Characteristics_Score__c":8,"No_of_Age_at_Onset__c":1,"Description_Source__c":"MONDO:0014611","Disease_Description__c":"Any fatal multiple mitochondrial dysfunctions syndrome in which the cause of the disease is a mutation in the ISCA2 gene.","GARD_Name__c":"Multiple mitochondrial dysfunctions syndrome 4","GARD_Synonym__c":"fatal multiple mitochondrial dysfunctions syndrome caused by mutation in isca2; isca2 fatal multiple mitochondrial dysfunctions syndrome; mmds4; mmds4 - multiple mitochondrial dysfunctions syndrome type 4; multiple mitochondrial dysfunctions syndrome type 4","Curated_Disease_Description_Source__c":"PlainLanguagePilotV2-Jan24","Curated_Disease_Description__c":"Multiple mitochondrial dysfunctions syndrome type 4 is a rare, genetic, neurometabolic disease. It is characterized by the loss of previously acquired skills. People with this syndrome may have vision problems including involuntary eye movements (nystagmus). They may have problems with the white matter portions of the brain (diffuse white matter disease) during infancy. Babies and children with this condition usually have decreased muscle tone. This is due to damage to the central nervous system (central hypotonia). This damage progresses to involuntary muscle contractions (limb spasticity) and overactive reflexes (hyperreflexia). Recurrent chest infections and seizures may also occur. As the disease progresses, multiple regions of the brain can become damaged.","Curated_USA_Estimate_Source__c":null,"Curated_USA_Estimate__c":"1,000","Age_at_Onset_Snippet_Text__c":"as an Infant","SourceID__c":"ORPHA:457406","Deprecated__c":"No","Disease_Concept_Type__c":"Rare Disease Entity","MONDO_ID__c":"MONDO:0014611","ORPHANET_ID__c":"ORPHA:457406","Replaced_By_ID__c":null,"Display_Spanish_Disease_Name__c":"Síndrome de disfunción mitocondrial múltiple tipo 4","Spanish_Description_Source__c":null,"Spanish_Description__c":null,"Spanish_Disease_Name__c":"síndrome de disfunción mitocondrial múltiple tipo 4","Spanish_GARD_Synonym__c":null,"Category_Linearization__c":"ORPHA:68367","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":"Multiple mitochondrial dysfunctions syndrome type 4 is a rare, genetic, neurometabolic disease. It is characterized by the loss of previously acquired skills. People with this syndrome may have vision problems including involuntary eye movements (nystagmus). They may have problems with the white matter portions of the brain (diffuse white matter disease) during infancy. Babies and children with this condition usually have decreased muscle tone. This is due to damage to the central nervous system (central hypotonia). This damage progresses to involuntary muscle contractions (limb spasticity) and overactive reflexes (hyperreflexia). Recurrent chest infections and seizures may also occur. As the disease progresses, multiple regions of the brain can become damaged.","Curated_Disease_Description_Source__c":"PlainLanguagePilotV2-Jan24","GARD_Synonym__c":"fatal multiple mitochondrial dysfunctions syndrome caused by mutation in isca2; isca2 fatal multiple mitochondrial dysfunctions syndrome; mmds4; mmds4 - multiple mitochondrial dysfunctions syndrome type 4; multiple mitochondrial dysfunctions syndrome type 4","Name":"Multiple mitochondrial dysfunctions syndrome 4","Curated_USA_Estimate__c":"1,000","estimateUsa":"1,000"}],"Organization_Supported_Diseases__c":[{"Account_Name__c":"United Mitochondrial Disease Foundation","Website__c":"https://www.umdf.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":"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":"Ophthalmology","Tag_Category__c":"Specialist"},{"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":"Leukodystrophy","Tag_Category__c":"Account;Cause;Disease Category","category_description":"Leukodystrophies are a group of genetic neurological diseases that affect the white matter of the brain and spinal cord.","curated_tag_name":"Leukodystrophies"},{"Tag_Name__c":"Neuro-Ophthalmology","Tag_Category__c":"Specialist","curated_tag_name":"Neuro-ophthalmic diseases"},{"Tag_Name__c":"Pediatrics","Tag_Category__c":"Specialist"}],"Age_At_Onset__c":[{"Age_At_Onset__c":"Infancy","Provided_By__c":"ORPHA:457406"}],"External_Identifier_Disease__c":[{"URL__c":"https://www.ncbi.nlm.nih.gov/books/NBK481904","Source__c":"Gene Review","Xref__c":"NBK481904"},{"URL__c":"https://uts.nlm.nih.gov/uts/umls/concept/C4225348","Source__c":"C4225348","Xref__c":"C4225348"},{"URL__c":"https://www.omim.org/entry/616370","Source__c":"C4225348; MONDO:0014611; ORPHA:457406","Xref__c":"OMIM:616370"},{"URL__c":"https://www.ebi.ac.uk/ols4/ontologies/doid/classes?obo_id=DOID%3A0080136","Source__c":"MONDO:0014611","Xref__c":"DOID:0080136"},{"URL__c":"https://www.orpha.net/en/disease/detail/457406","Source__c":"C4225348; MONDO:0014611; ORPHA:457406","Xref__c":"ORPHA:457406"},{"URL__c":"https://www.ncbi.nlm.nih.gov/medgen/?term=899010","Source__c":"C4225348","Xref__c":"MEDGEN:899010"},{"URL__c":"https://browser.ihtsdotools.org/?perspective=full&conceptId1=1208621008","Source__c":"C4225348","Xref__c":"1208621008"},{"URL__c":"http://purl.obolibrary.org/obo/MONDO_0014611","Source__c":"GARD:0017809","Xref__c":"MONDO:0014611"}],"GARD_Disease_Gene__c":[{"GeneSymbol__c":"ISCA2","Gene_Type__c":"protein-coding gene","Causal_Gene__c":true}],"Inheritance__c":["Autosomal recessive"],"GARD_Disease_Feature__c":[{"Provided_By__c":"OMIM:616370","Feature__r":{"HPO_Description__c":"The absence of wakefulness and consciousness, but in contrast to a coma, there is involuntary opening of the eyes and movements such as teeth grinding, yawning, or thrashing of the extremities.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0031358","HPO_Synonym__c":"Unresponsive wakefulness","HPO_Name__c":"Vegetative state","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:616370","Feature__r":{"HPO_Description__c":"A structural abnormality of the myelinated axons (white matter) located near the cerebral ventricles.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002518","HPO_Synonym__c":"Abnormality of the periventricular white matter","HPO_Name__c":"Abnormal periventricular white matter morphology","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:616370","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Complete lack of development of speech and language abilities.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001344","HPO_Synonym__c":"Absent speech development; Lack of language development; Lack of speech; No speech development; No speech or language development; Nonverbal","HPO_Name__c":"Absent speech","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:616370","Feature__r":{"HPO_Description__c":"Leukodystrophy refers to deterioration of white matter of the brain resulting from degeneration of myelin sheaths in the CNS. Their basic defect is directly related to the synthesis and maintenance of myelin membranes. Symmetric white matter involvement at MRI is a typical finding in patients with leukodystrophies.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002415","HPO_Synonym__c":"Degeneration of white matter of brain","HPO_Name__c":"Leukodystrophy","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:616370","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:616370","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001257","HPO_Synonym__c":"Involuntary muscle stiffness, contraction, or spasm; Muscle spasticity; Muscular spasticity","HPO_Name__c":"Spasticity","Feature_System__c":"Nervous System; Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:616370","Feature__r":{"HPO_Description__c":"Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001347","HPO_Synonym__c":"Increased deep tendon reflexes; Increased reflexes","HPO_Name__c":"Hyperreflexia","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:616370","Feature__r":{"HPO_Description__c":"Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000639","HPO_Synonym__c":"Involuntary, rapid, rhythmic eye movements","HPO_Name__c":"Nystagmus","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:616370","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Loss of developmental skills, as manifested by loss of developmental milestones.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002376","HPO_Synonym__c":"Loss of acquired milestones; Loss of developmental milestones; Loss of milestones; Mental deterioration in childhood; Neurodevelopmental regression; Psychomotor regression; Psychomotor regression beginning in infancy; Psychomotor regression in infants; Psychomotor regression, progressive","HPO_Name__c":"Developmental regression","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:616370","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"A reduction in the activity of the mitochondrial respiratory chain complex I, which is part of the electron transport chain in mitochondria.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0011923","HPO_Name__c":"Decreased activity of mitochondrial complex I","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"OMIM:616370","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"A profound delay in the achievement of motor or mental milestones in the domains of development of a child.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0012736","HPO_Synonym__c":"Global developmental delay, profound","HPO_Name__c":"Profound global developmental delay","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:616370","Feature__r":{"HPO_Description__c":"Visual impairment (or vision impairment) is vision loss (of a person) to such a degree as to qualify as an additional support need through a significant limitation of visual capability resulting from either disease, trauma, or congenital or degenerative conditions that cannot be corrected by conventional means, such as refractive correction, medication, or surgery.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000505","HPO_Synonym__c":"Impaired vision; Loss of eyesight; Poor vision; Visual impairment","HPO_Name__c":"Visual impairment","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:616370","HPO_Frequency__c":"Very frequent (80-99%)","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"}}],"tags":{"Cause":["Genetics","Inborn Errors of Metabolism","Mitochondrial","Leukodystrophy"],"Disease Category":["Genetics","Neurology","Inborn Errors of Metabolism","Mitochondrial","Leukodystrophy"],"Specialist":["Genetics","Neurology","Ophthalmology","Neuro-Ophthalmology","Pediatrics"],"Account":["Mitochondrial","Leukodystrophy"]},"synonyms":["fatal multiple mitochondrial dysfunctions syndrome caused by mutation in isca2"," isca2 fatal multiple mitochondrial dysfunctions syndrome"," mmds4"," mmds4 - multiple mitochondrial dysfunctions syndrome type 4"," multiple mitochondrial dysfunctions syndrome type 4"]}