{"Name":"Hypomyelinating leukodystrophy 9","DiseaseID__c":"GARD:0017734","id":17734,"encodedName":"hypomyelinating-leukodystrophy-9","IsDeleted":false,"Disease_Name_Full__c":"Hypomyelinating leukodystrophy 9","Xref_IDs__c":"C4015323; DOID:0060791; MEDGEN:863760; MONDO:0014506; OMIM:616140; ORPHA:438114","USA_Estimate__c":"1,000","No_of_Specialist_Tagsa__c":4,"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:0014506","Disease_Description__c":"Any leukodystrophy in which the cause of the disease is a mutation in the RARS gene.","GARD_Name__c":"Hypomyelinating leukodystrophy 9","GARD_Synonym__c":"arginyl-trna synthetase 1-related autosomal recessive hypomyelinating leukodystrophy; hld9; hypomyelinating leukodystrophy type 9; leukodystrophy caused by mutation in rars; leukodystrophy, hypomyelinating, type 9; rars leukodystrophy; rars-related autosomal recessive hypomyelinating leukodystrophy","Curated_Disease_Description_Source__c":"ORPHA:438114","Curated_Disease_Description__c":"A rare, genetic leukodystrophy characterized by developmental delay, increased muscle tone leading later to spasticity, mild ataxia, nystagmus, dysarthria, intentional tremor, and mild intellectual disability. Brain imaging reveals supratentorial and infratentorial hypomyelination.","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:438114","Deprecated__c":"No","Disease_Concept_Type__c":"Rare Disease Entity","MONDO_ID__c":"MONDO:0014506","ORPHANET_ID__c":"ORPHA:438114","Replaced_By_ID__c":null,"Display_Spanish_Disease_Name__c":"Leucodistrofia hipomielinizante autosómica recesiva asociada a rars","Spanish_Description_Source__c":null,"Spanish_Description__c":null,"Spanish_Disease_Name__c":"leucodistrofia hipomielinizante autosómica recesiva asociada a rars","Spanish_GARD_Synonym__c":null,"Category_Linearization__c":"ORPHA:98006","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":"A rare, genetic leukodystrophy characterized by developmental delay, increased muscle tone leading later to spasticity, mild ataxia, nystagmus, dysarthria, intentional tremor, and mild intellectual disability. Brain imaging reveals supratentorial and infratentorial hypomyelination.","Curated_Disease_Description_Source__c":"ORPHA:438114","GARD_Synonym__c":"arginyl-trna synthetase 1-related autosomal recessive hypomyelinating leukodystrophy; hld9; hypomyelinating leukodystrophy type 9; leukodystrophy caused by mutation in rars; leukodystrophy, hypomyelinating, type 9; rars leukodystrophy; rars-related autosomal recessive hypomyelinating leukodystrophy","Name":"Hypomyelinating leukodystrophy 9","Curated_USA_Estimate__c":"1,000","estimateUsa":"1,000"}],"Organization_Supported_Diseases__c":[{"Account_Name__c":"Alex The Leukodystrophy Charity","Website__c":"https://www.alextlc.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":"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":"Neurodevelopmental disabilities","Tag_Category__c":"Specialist","curated_tag_name":"Neurodevelopmental disabilities"},{"Tag_Name__c":"Pediatrics","Tag_Category__c":"Specialist"}],"Age_At_Onset__c":[{"Age_At_Onset__c":"Infancy","Provided_By__c":"ORPHA:438114"},{"Age_At_Onset__c":"Neonatal","Provided_By__c":"ORPHA:438114"}],"External_Identifier_Disease__c":[{"URL__c":"https://uts.nlm.nih.gov/uts/umls/concept/C4015323","Source__c":"C4015323","Xref__c":"C4015323"},{"URL__c":"https://www.ncbi.nlm.nih.gov/medgen/?term=863760","Source__c":"C4015323","Xref__c":"MEDGEN:863760"},{"URL__c":"https://www.omim.org/entry/616140","Source__c":"C4015323; MONDO:0014506; ORPHA:438114","Xref__c":"OMIM:616140"},{"URL__c":"https://www.ebi.ac.uk/ols4/ontologies/doid/classes?obo_id=DOID%3A0060791","Source__c":"MONDO:0014506","Xref__c":"DOID:0060791"},{"URL__c":"https://www.orpha.net/en/disease/detail/438114","Source__c":"C4015323; MONDO:0014506; ORPHA:438114","Xref__c":"ORPHA:438114"},{"URL__c":"http://purl.obolibrary.org/obo/MONDO_0014506","Source__c":"GARD:0017734","Xref__c":"MONDO:0014506"},{"URL__c":"https://browser.ihtsdotools.org/?perspective=full&conceptId1=1220600004","Source__c":"C4015323","Xref__c":"1220600004"}],"GARD_Disease_Gene__c":[{"GeneSymbol__c":"RARS1","Gene_Type__c":"protein-coding gene","Causal_Gene__c":true}],"Inheritance__c":["Autosomal recessive"],"GARD_Disease_Feature__c":[{"Provided_By__c":"ORPHA:438114","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Head circumference below 2 standard deviations below the mean for age and sex.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000252","HPO_Synonym__c":"Abnormally small cranium; Abnormally small skull; Decreased circumference of cranium; Decreased size of cranium; Decreased size of skull; Reduced head circumference; small cranium; Small head circumference","HPO_Name__c":"Microcephaly","Feature_System__c":"Nervous System; Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:438114","HPO_Frequency__c":"Frequent (30-79%)","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":"ORPHA:438114","HPO_Frequency__c":"Frequent (30-79%)","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":"ORPHA:438114","HPO_Frequency__c":"Frequent (30-79%)","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":"ORPHA:438114","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"The term gait disturbance can refer to any disruption of the ability to walk.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001288","HPO_Synonym__c":"Abnormal gait; Abnormal walk; Difficulty in walking; Gait abnormalities; Gait difficulties; Gait disturbances; Impaired gait; Walking disability","HPO_Name__c":"Gait disturbance","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:438114","HPO_Frequency__c":"Frequent (30-79%)","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":"ORPHA:438114","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001332","HPO_Synonym__c":"Dystonic movements","HPO_Name__c":"Dystonia","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:438114","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001260","HPO_Synonym__c":"Difficulty articulating speech; Dysarthric speech","HPO_Name__c":"Dysarthria","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:438114","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0007153","HPO_Name__c":"Progressive extrapyramidal movement disorder","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:438114","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Reduced amount of myelin in the nervous system resulting from defective myelinogenesis in the white matter of the central nervous system.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0006808","HPO_Synonym__c":"Hypomyelination of the brain","HPO_Name__c":"Cerebral hypomyelination","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:438114","HPO_Frequency__c":"Frequent (30-79%)","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":"ORPHA:438114","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"A brighter than expected signal on magnetic resonance imaging emanating from the cerebral white matter.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0030890","HPO_Synonym__c":"White matter hyperintensity","HPO_Name__c":"Hyperintensity of cerebral white matter on MRI","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Imaging_MRI"}},{"Provided_By__c":"ORPHA:438114","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"A focal-onset seizure is a type of seizure originating within networks limited to one hemisphere. They may be discretely localized or more widely distributed, and may originate in subcortical structures.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0007359","HPO_Synonym__c":"Focal onset seizure; Focal seizure; Focal seizures; Focal-onset seizures; Partial seizure; Partial seizures; Seizure affecting one half of brain","HPO_Name__c":"Focal-onset seizure","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:438114","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Bilateral impairment of the function of the cranial nerves 9-12, which control musculature involved in eating, swallowing, and speech. Pseudobulbar paralysis is characterized clinically by dysarthria, dysphonia, and dysphagia with bifacial paralysis, and may be accompanied by Pseudobulbar behavioral symptoms such as enforced crying and laughing.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0007024","HPO_Synonym__c":"Pseudobulbar palsy; Pseudobulbar syndrome","HPO_Name__c":"Pseudobulbar paralysis","Feature_System__c":"Nervous System; Digestive System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:438114","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Diffuse unlocalised atrophy affecting the cerebrum.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002506","HPO_Synonym__c":"Cerebral atrophy, diffuse","HPO_Name__c":"Diffuse cerebral atrophy","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:438114","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"A type of ataxia characterized by the inability to carry out movements with the correct range and motion across the plane of more than one joint related to incorrect estimation of the distances required for targeted movements.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001310","HPO_Synonym__c":"Lack of coordination of movement","HPO_Name__c":"Dysmetria","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:438114","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"A cessation of the development of a child in the areas of motor skills, speech and language, cognitive skills, and social and/or emotional skills.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0007281","HPO_Synonym__c":"Developmental arrest","HPO_Name__c":"Developmental stagnation","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:438114","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"A type of kinetic tremor that occurs during target directed movement is called intention tremor. That is, an oscillatory cerebellar ataxia that tends to be absent when the limbs are inactive and during the first part of voluntary movement but worsening as the movement continues and greater precision is required (e.g., in touching a target such as the patient's nose or a physician's finger).","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002080","HPO_Name__c":"Intention tremor","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:438114","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Spasticity (velocity-dependent increase in tonic stretch reflexes with increased muscle tone and hyperexcitable tendon reflexes) in the muscles of the lower limbs, hips, and pelvis.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002061","HPO_Synonym__c":"Lower extremities spasticity; Lower extremity spasticity; Spastic lower extremities; Spastic lower extremity; Spastic lower limb; Spastic lower limbs; Spasticity in lower extremities; Spasticity in lower extremity; Spasticity in lower limb; Spasticity in lower limbs; Spasticity of lower extremities; Spasticity of lower extremity; Spasticity of lower limb; Spasticity of lower limbs","HPO_Name__c":"Lower limb spasticity","Feature_System__c":"Nervous System; Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:438114","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"A reduced frequency or duration of eye contact.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000817","HPO_Synonym__c":"Poor eye contact","HPO_Name__c":"Reduced eye contact","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:438114","HPO_Frequency__c":"Occasional (5-29%)","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":"ORPHA:438114","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"A complete lack of the ability to track objects with the ocular smooth pursuit system, a class of rather slow eye movements that minimizes retinal target motion.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0007179","HPO_Name__c":"Absent smooth pursuit","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:438114","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Mild intellectual disability (ID) is defined as a type of ID characterized by mildly sub-average adaptive functioning and intellectual functioning, with an intelligence quotient (IQ) the range of 50-69.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001256","HPO_Synonym__c":"Intellectual disability, mild; Mental retardation, borderline-mild; Mild and nonprogressive mental retardation; Mild mental retardation","HPO_Name__c":"Mild intellectual disability","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:438114","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0006895","HPO_Name__c":"Lower limb hypertonia","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:438114","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Underdevelopment of the corpus callosum.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002079","HPO_Synonym__c":"Corpus callosum hypoplasia; Hypoplasia of corpus callosum; Hypoplastic corpus callosum; Underdevelopment of part of brain called corpus callosum","HPO_Name__c":"Hypoplasia of the corpus callosum","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:438114","HPO_Frequency__c":"Occasional (5-29%)","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":"ORPHA:438114","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0008936","HPO_Synonym__c":"Low muscle tone in trunk; Muscular hypotonia of the trunk; Truncal hypotonia","HPO_Name__c":"Axial hypotonia","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}}],"tags":{"Cause":["Genetics","Leukodystrophy"],"Disease Category":["Genetics","Neurology","Leukodystrophy"],"Specialist":["Genetics","Neurology","Neurodevelopmental disabilities","Pediatrics"],"Account":["Leukodystrophy"]},"synonyms":["arginyl-trna synthetase 1-related autosomal recessive hypomyelinating leukodystrophy"," hld9"," hypomyelinating leukodystrophy type 9"," leukodystrophy caused by mutation in rars"," leukodystrophy, hypomyelinating, type 9"," rars leukodystrophy"," rars-related autosomal recessive hypomyelinating leukodystrophy"]}