{"Name":"Spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy","DiseaseID__c":"GARD:0017964","id":17964,"encodedName":"spastic-ataxia-8-autosomal-recessive-with-hypomyelinating-leukodystrophy","IsDeleted":false,"Disease_Name_Full__c":"Spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy","Xref_IDs__c":"C4479653; DOID:0080252; MEDGEN:1382553; MONDO:0033043; OMIM:617560; ORPHA:527497","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":3,"Disease_Characteristics_Score__c":8,"No_of_Age_at_Onset__c":2,"Description_Source__c":"ORPHA:527497","Disease_Description__c":"A rare leukodystrophy characterized by a spectrum of progressive neurologic manifestations comprising rapidly progressive early-onset nystagmus, spastic tetraplegia, and visual and hearing impairment, resulting in death in early childhood, as well as later onset of slowly progressive complex spastic ataxia with pyramidal and cerebellar symptoms and loss of developmental milestones. Brain imaging shows diffuse hypomyelination of the subcortical and deep white matter, cerebellar atrophy, and diffuse spinal cord volume loss.","GARD_Name__c":"Spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy","GARD_Synonym__c":"autosomal recessive hypomyelinating leukodystrophy-progressive spastic ataxia; autosomal recessive hypomyelinating leukodystrophy, progressive spastic ataxia; nk6 homeobox 2-related autosomal recessive hypomyelinating leukodystrophy; nkx6-2-related autosomal recessive hypomyelinating leukodystrophy; spax8; spax8 - spastic ataxia 8","Curated_Disease_Description_Source__c":"PlainLanguagePilotV2-Jan24","Curated_Disease_Description__c":"NKX6-2-related autosomal recessive hypomyelinating leukodystrophy is a rare, genetic, neurological disease spectrum. It is progressive, which means the symptoms get worse over time. Some present with symptoms at birth. For them, the disease is characterized by involuntary eye movements (nystagmus). They also have severe difficulty moving and controlling muscles throughout the body (spastic tetraplegia). Those who have symptoms starting at birth may also have problems with sight and hearing. Some start to experience symptoms after the first year. For these people, symptoms may include uncoordinated or jerky movement (spastic ataxia). They may also have a loss of previously acquired developmental skills. These people may have other brain-related problems with coordination, balance, and voluntary movements. People with this condition may have an atypical brain structure. This includes decreased myelin in their white matter. Other brain structure differences include a shrinking cerebellum. There may also be changes to the spinal cord volume.","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:527497","Deprecated__c":"No","Disease_Concept_Type__c":"Rare Disease Entity","MONDO_ID__c":"MONDO:0033043","ORPHANET_ID__c":"ORPHA:527497","Replaced_By_ID__c":null,"Display_Spanish_Disease_Name__c":"Leucodistrofia hipomielinizante autosómica recesiva asociada a nkx6-2","Spanish_Description_Source__c":null,"Spanish_Description__c":null,"Spanish_Disease_Name__c":"leucodistrofia hipomielinizante autosómica recesiva asociada a nkx6-2","Spanish_GARD_Synonym__c":"leucodistrofia hipomielinizante autosómica recesiva-ataxia espástica progresiva; spax8","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":"NKX6-2-related autosomal recessive hypomyelinating leukodystrophy is a rare, genetic, neurological disease spectrum. It is progressive, which means the symptoms get worse over time. Some present with symptoms at birth. For them, the disease is characterized by involuntary eye movements (nystagmus). They also have severe difficulty moving and controlling muscles throughout the body (spastic tetraplegia). Those who have symptoms starting at birth may also have problems with sight and hearing. Some start to experience symptoms after the first year. For these people, symptoms may include uncoordinated or jerky movement (spastic ataxia). They may also have a loss of previously acquired developmental skills. These people may have other brain-related problems with coordination, balance, and voluntary movements. People with this condition may have an atypical brain structure. This includes decreased myelin in their white matter. Other brain structure differences include a shrinking cerebellum. There may also be changes to the spinal cord volume.","Curated_Disease_Description_Source__c":"PlainLanguagePilotV2-Jan24","GARD_Synonym__c":"autosomal recessive hypomyelinating leukodystrophy-progressive spastic ataxia; autosomal recessive hypomyelinating leukodystrophy, progressive spastic ataxia; nk6 homeobox 2-related autosomal recessive hypomyelinating leukodystrophy; nkx6-2-related autosomal recessive hypomyelinating leukodystrophy; spax8; spax8 - spastic ataxia 8","Name":"Spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy","Curated_USA_Estimate__c":"1,000","estimateUsa":"1,000"}],"Organization_Supported_Diseases__c":[{"Account_Name__c":"Ataxia UK","Website__c":"https://www.ataxia.org.uk/"},{"Account_Name__c":"National Ataxia Foundation","Website__c":"https://ataxia.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":"Ataxia","Tag_Category__c":"Account","curated_tag_name":"Ataxia"},{"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":"Childhood","Provided_By__c":"ORPHA:527497"},{"Age_At_Onset__c":"Infancy","Provided_By__c":"ORPHA:527497"}],"External_Identifier_Disease__c":[{"URL__c":"https://www.ncbi.nlm.nih.gov/books/NBK531509","Source__c":"Gene Review","Xref__c":"NBK531509"},{"URL__c":"https://www.omim.org/entry/617560","Source__c":"C4479653; MONDO:0033043; ORPHA:527497","Xref__c":"OMIM:617560"},{"URL__c":"https://www.ncbi.nlm.nih.gov/medgen/?term=1382553","Source__c":"C4479653","Xref__c":"MEDGEN:1382553"},{"URL__c":"https://www.ebi.ac.uk/ols4/ontologies/doid/classes?obo_id=DOID%3A0080252","Source__c":"MONDO:0033043","Xref__c":"DOID:0080252"},{"URL__c":"https://uts.nlm.nih.gov/uts/umls/concept/C4479653","Source__c":"C4479653","Xref__c":"C4479653"},{"URL__c":"https://www.orpha.net/en/disease/detail/527497","Source__c":"C4479653; MONDO:0033043; ORPHA:527497","Xref__c":"ORPHA:527497"},{"URL__c":"http://purl.obolibrary.org/obo/MONDO_0033043","Source__c":"GARD:0017964","Xref__c":"MONDO:0033043"},{"URL__c":"https://browser.ihtsdotools.org/?perspective=full&conceptId1=1217379007","Source__c":"C4479653","Xref__c":"1217379007"}],"GARD_Disease_Gene__c":[{"GeneSymbol__c":"NKX6-2","Gene_Type__c":"protein-coding gene","Causal_Gene__c":true}],"Inheritance__c":["Autosomal recessive"],"GARD_Disease_Feature__c":[{"Provided_By__c":"ORPHA:527497","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"A head tremor of moderate speed (3 to 4 Hz) in the anterior-posterior direction.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002599","HPO_Name__c":"Head titubation","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:527497","HPO_Frequency__c":"Excluded (0%)","Feature__r":{"HPO_Description__c":"Painful sensations elicited by a nonpainful cutaneous stimulus such as a light touch or gentle stroking over affected areas of the body. Sometimes referred to as hyperpathia or hyperalgesia. Often perceived as an intense burning, dyesthesias may outlast the stimulus by several seconds.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0012534","HPO_Synonym__c":"Dysaesthesia; Hyperalgesia; Hyperpathia","HPO_Name__c":"Dysesthesia","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:527497","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:527497","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:527497","HPO_Frequency__c":"Frequent (30-79%)","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":"ORPHA:527497","HPO_Frequency__c":"Uncommon (<1-4%)","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:527497","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Abnormally increased hair growth referring to a male pattern of body hair (androgenic hair).","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001007","HPO_Synonym__c":"Excessive hairiness","HPO_Name__c":"Hirsutism","Feature_System__c":"Skin System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:527497","HPO_Frequency__c":"Occasional (5-29%)","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":"ORPHA:527497","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"The presence of an abnormal lateral curvature of the spine.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002650","HPO_Name__c":"Scoliosis","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:527497","HPO_Frequency__c":"Very frequent (80-99%)","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:527497","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Reduced amount of myelin in the central nervous system resulting from defective myelinogenesis.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0003429","HPO_Name__c":"CNS hypomyelination","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:527497","HPO_Frequency__c":"Uncommon (<1-4%)","Feature__r":{"HPO_Description__c":"The term intellectual disability or intellectual developmental disorder is used to describe significantly sub-average intellectual and adaptive functioning based on clinical assessment and as measured by individually administered, appropriately normed, standardized and validated tests of intellectual functioning and adaptive behavior, with onset during the developmental period from infancy through adolescence.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001249","HPO_Synonym__c":"Intellectual disability; Mental deficiency; Mental retardation; Mental retardation, nonspecific; Mental-retardation; Nonprogressive intellectual disability; Nonprogressive mental retardation","HPO_Name__c":"Intellectual disability","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:527497","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Spasticity that increases in degree with time.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002191","HPO_Synonym__c":"Spasticity, progressive","HPO_Name__c":"Progressive spasticity","Feature_System__c":"Nervous System; Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:527497","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001272","HPO_Synonym__c":"Atrophic cerebellum; Degeneration of cerebellum","HPO_Name__c":"Cerebellar atrophy","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:527497","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001250","HPO_Synonym__c":"Epileptic seizure; Seizures","HPO_Name__c":"Seizure","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:527497","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:527497","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Functional neurological abnormalities related to dysfunction of the pyramidal tract.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0007256","HPO_Synonym__c":"Corticospinal signs; Pyramidal signs; Pyramidal tract signs","HPO_Name__c":"Abnormal pyramidal sign","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:527497","HPO_Frequency__c":"Frequent (30-79%)","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":"ORPHA:527497","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Sudden-onset episode of abnormal, involuntary eye movements.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0007704","HPO_Synonym__c":"Abnormal eye movements, paroxysmal","HPO_Name__c":"Paroxysmal involuntary eye movements","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:527497","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Saccadic undershoot, i.e., a saccadic eye movement that has less than the magnitude that would be required to gain fixation of the object.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000571","HPO_Name__c":"Hypometric saccades","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:527497","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:527497","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000486","HPO_Synonym__c":"Cross-eyed; Squint; Squint eyes","HPO_Name__c":"Strabismus","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:527497","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:527497","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:527497","HPO_Frequency__c":"Very frequent (80-99%)","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"}}],"tags":{"Cause":["Genetics","Leukodystrophy"],"Disease Category":["Genetics","Neurology","Leukodystrophy"],"Specialist":["Genetics","Neurology","Neurodevelopmental disabilities","Pediatrics"],"Account":["Leukodystrophy","Ataxia"]},"synonyms":["autosomal recessive hypomyelinating leukodystrophy-progressive spastic ataxia"," autosomal recessive hypomyelinating leukodystrophy, progressive spastic ataxia"," nk6 homeobox 2-related autosomal recessive hypomyelinating leukodystrophy"," nkx6-2-related autosomal recessive hypomyelinating leukodystrophy"," spax8"," spax8 - spastic ataxia 8"]}