{"Name":"Metachromatic leukodystrophy","DiseaseID__c":"GARD:0003230","id":3230,"encodedName":"metachromatic-leukodystrophy","IsDeleted":false,"Disease_Name_Full__c":"Metachromatic leukodystrophy","Xref_IDs__c":"238031009; 396338004; 423022235; 66521008; C0023522; C61251; D007966; DOID:10581; E75.25; MEDGEN:6071; MONDO:0018868; ORPHA:512","USA_Estimate__c":"50,000","No_of_Specialist_Tagsa__c":8,"No_of_ClinGen_records__c":0,"No_of_GeneReviews__c":0,"No_of_HHS_records__c":2,"World_Estimate__c":"80,000 to 800,000","No_of_HRSA_records__c":0,"Evidence_Based_Score__c":2,"No_of_Disease_Descriptions__c":5,"Disease_Characteristics_Score__c":8,"No_of_Age_at_Onset__c":4,"Description_Source__c":"MONDO:0018868","Disease_Description__c":"A rare lysosomal disease characterized by accumulation of sulfatides in the central and peripheral nervous system due to deficiency of the enzyme arylsulfatase A, leading to demyelination. Three clinical subtypes can be distinguished based on the age of onset: late infantile, juvenile, and adult. Lead symptoms are deterioration in motor or cognitive function or behavioral problems, depending on the subtype, all eventually culminating in a decerebrated state and death after a highly variable disease course and duration. Mode of inheritance is autosomal recessive.","GARD_Name__c":"Metachromatic leukodystrophy","GARD_Synonym__c":"arsa deficiency; arylsulfatase a deficiency; cerebral sclerosis diffuse metachromatic form; cerebroside sulfatase deficiency; deficiency of cerebroside-sulfatase; familial progressive cerebral sclerosis; metachromatic leucodystrophy; metachromatic leukoencephalopathy; metachromatic leukoencephaly; mld; mld - metachromatic leucodystrophy; scholz cerebral sclerosis; sulfatide lipidosis; sulfatide lipoidosis; van bogaert-nijssen disease","Curated_Disease_Description_Source__c":"GARD:0003230","Curated_Disease_Description__c":"Metachromatic leukodystrophy is an inherited disorder characterized by the accumulation of fats called sulfatides in cells. This accumulation especially affects cells in the nervous system that produce myelin, the substance that insulates and protects nerves. Nerve cells covered by myelin make up a tissue called white matter. Sulfatide accumulation in myelin-producing cells causes progressive destruction of white matter (leukodystrophy) throughout the nervous system, including in the brain and spinal cord (the central nervous system) and the nerves connecting the brain and spinal cord to muscles and sensory cells that detect sensations such as touch, pain, heat, and sound (the peripheral nervous system). In people with metachromatic leukodystrophy, white matter damage causes progressive deterioration of intellectual functions and motor skills, such as the ability to walk. Affected individuals also develop loss of sensation in the extremities (peripheral neuropathy), incontinence, seizures, paralysis, an inability to speak, blindness, and hearing loss. Eventually they lose awareness of their surroundings and become unresponsive. While neurological problems are the primary feature of metachromatic leukodystrophy, effects of sulfatide accumulation on other organs and tissues have been reported, most often involving the gallbladder. The most common form of metachromatic leukodystrophy, affecting about 50 to 60 percent of all individuals with this disorder, is called the late infantile form. This form of the disorder usually appears in the second year of life. Affected children lose any speech they have developed, become weak, and develop problems with walking (gait disturbance). As the disorder worsens, muscle tone generally first decreases, and then increases to the point of rigidity. Individuals with the late infantile form of metachromatic leukodystrophy typically do not survive past childhood. In 20 to 30 percent of individuals with metachromatic leukodystrophy, onset occurs between the age of 4 and adolescence. In this juvenile form, the first signs of the disorder may be behavioral problems and increasing difficulty with schoolwork. Progression of the disorder is slower than in the late infantile form, and affected individuals may survive for about 20 years after diagnosis. The adult form of metachromatic leukodystrophy affects approximately 15 to 20 percent of individuals with the disorder. In this form, the first symptoms appear during the teenage years or later. Often behavioral problems such as alcohol use disorder, drug abuse, or difficulties at school or work are the first symptoms to appear. The affected individual may experience psychiatric symptoms such as delusions or hallucinations. People with the adult form of metachromatic leukodystrophy may survive for 20 to 30 years after diagnosis. During this time there may be some periods of relative stability and other periods of more rapid decline. Metachromatic leukodystrophy gets its name from the way cells with an accumulation of sulfatides appear when viewed under a microscope. The sulfatides form granules that are described as metachromatic, which means they pick up color differently than surrounding cellular material when stained for examination.","Curated_USA_Estimate_Source__c":null,"Curated_USA_Estimate__c":"50,000","Age_at_Onset_Snippet_Text__c":"at a variety of ages","SourceID__c":"ORPHA:512","Deprecated__c":"No","Disease_Concept_Type__c":"Rare Disease Grouping","MONDO_ID__c":"MONDO:0018868","ORPHANET_ID__c":"ORPHA:512","Replaced_By_ID__c":null,"Display_Spanish_Disease_Name__c":"Leucodistrofia metacromática","Spanish_Description_Source__c":"ORPHA:512","Spanish_Description__c":"Es una enfermedad lisosomal poco frecuente caracterizada por el acúmulo de sulfátidos en el sistema nervioso central y periférico debido a la deficiencia de la enzima arilsulfatasa A, que resulta en desmielinización. Se pueden distinguir tres subtipos clínicos según la edad de inicio: el infantil tardío, el juvenil y el adulto. Los síntomas principales son el deterioro de la función motora o cognitiva o los trastornos de conducta, dependiendo el subtipo, que finalmente conduce a un estado de descerebración y fallecimiento tras un curso y una duración de la enfermedad muy variables. El modo de herencia de la enfermedad es autosómico recesivo.","Spanish_Disease_Name__c":"leucodistrofia metacromática","Spanish_GARD_Synonym__c":"deficiencia de arilsulfatasa a; mld","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":"Metachromatic leukodystrophy is an inherited disorder characterized by the accumulation of fats called sulfatides in cells. This accumulation especially affects cells in the nervous system that produce myelin, the substance that insulates and protects nerves. Nerve cells covered by myelin make up a tissue called white matter. Sulfatide accumulation in myelin-producing cells causes progressive destruction of white matter (leukodystrophy) throughout the nervous system, including in the brain and spinal cord (the central nervous system) and the nerves connecting the brain and spinal cord to muscles and sensory cells that detect sensations such as touch, pain, heat, and sound (the peripheral nervous system). In people with metachromatic leukodystrophy, white matter damage causes progressive deterioration of intellectual functions and motor skills, such as the ability to walk. Affected individuals also develop loss of sensation in the extremities (peripheral neuropathy), incontinence, seizures, paralysis, an inability to speak, blindness, and hearing loss. Eventually they lose awareness of their surroundings and become unresponsive. While neurological problems are the primary feature of metachromatic leukodystrophy, effects of sulfatide accumulation on other organs and tissues have been reported, most often involving the gallbladder. The most common form of metachromatic leukodystrophy, affecting about 50 to 60 percent of all individuals with this disorder, is called the late infantile form. This form of the disorder usually appears in the second year of life. Affected children lose any speech they have developed, become weak, and develop problems with walking (gait disturbance). As the disorder worsens, muscle tone generally first decreases, and then increases to the point of rigidity. Individuals with the late infantile form of metachromatic leukodystrophy typically do not survive past childhood. In 20 to 30 percent of individuals with metachromatic leukodystrophy, onset occurs between the age of 4 and adolescence. In this juvenile form, the first signs of the disorder may be behavioral problems and increasing difficulty with schoolwork. Progression of the disorder is slower than in the late infantile form, and affected individuals may survive for about 20 years after diagnosis. The adult form of metachromatic leukodystrophy affects approximately 15 to 20 percent of individuals with the disorder. In this form, the first symptoms appear during the teenage years or later. Often behavioral problems such as alcohol use disorder, drug abuse, or difficulties at school or work are the first symptoms to appear. The affected individual may experience psychiatric symptoms such as delusions or hallucinations. People with the adult form of metachromatic leukodystrophy may survive for 20 to 30 years after diagnosis. During this time there may be some periods of relative stability and other periods of more rapid decline. Metachromatic leukodystrophy gets its name from the way cells with an accumulation of sulfatides appear when viewed under a microscope. The sulfatides form granules that are described as metachromatic, which means they pick up color differently than surrounding cellular material when stained for examination.","Curated_Disease_Description_Source__c":"GARD:0003230","GARD_Synonym__c":"arsa deficiency; arylsulfatase a deficiency; cerebral sclerosis diffuse metachromatic form; cerebroside sulfatase deficiency; deficiency of cerebroside-sulfatase; familial progressive cerebral sclerosis; metachromatic leucodystrophy; metachromatic leukoencephalopathy; metachromatic leukoencephaly; mld; mld - metachromatic leucodystrophy; scholz cerebral sclerosis; sulfatide lipidosis; sulfatide lipoidosis; van bogaert-nijssen disease","Name":"Metachromatic leukodystrophy","Curated_USA_Estimate__c":"50,000","estimateUsa":"50,000"}],"Organization_Supported_Diseases__c":[{"Account_Name__c":"Society for Mucopolysaccharide Diseases","Website__c":"https://www.mpssociety.org.uk/"},{"Account_Name__c":"MLD Support Association UK","Website__c":"https://www.mldsupportuk.org.uk/"},{"Account_Name__c":"Childhood Dementia Initiative","Website__c":"https://www.childhooddementia.org/"},{"Account_Name__c":"Bethany’s Hope Foundation","Website__c":"https://bethanyshope.org/"},{"Account_Name__c":"Chloe's Fight Rare Disease Foundation","Website__c":"https://www.chloesfight.org/"},{"Account_Name__c":"European Leukodystrophies Association","Website__c":"https://ela-asso.com/en/"},{"Account_Name__c":"Gavin Flying for a Cure","Website__c":"https://tggf.ie/about/"},{"Account_Name__c":"Leukodystrophy Australia","Website__c":"https://www.leuko.org.au/"},{"Account_Name__c":"Leukodystrophy Resource & Research Organisation","Website__c":"https://www.facebook.com/LeukodystrophyRRO/"},{"Account_Name__c":"MSD Action Foundation","Website__c":"http://www.savingdylan.com/"},{"Account_Name__c":"RARE-X","Website__c":"https://rare-x.org/patients/"},{"Account_Name__c":"The Calliope Joy Foundation","Website__c":"https://www.facebook.com/thecalliopejoyfoundation/"},{"Account_Name__c":"Alianza Iberoamericana de Enfermedades Raras o Poco Frecuentes","Website__c":"https://aliber.org/web/"},{"Account_Name__c":"Federación Mexicana de Enfermedades Raras (FEMEXER)","Website__c":"http://www.femexer.org/"},{"Account_Name__c":"Federación Española de Enfermedades Raras","Website__c":"https://enfermedades-raras.org/"},{"Account_Name__c":"Federación Colombiana de Enfermedades Raras","Website__c":"http://www.fecoer.org"},{"Account_Name__c":"Federación Argentina de Enfermedades Poco Frecuentes","Website__c":"https://fadepof.org.ar/"},{"Account_Name__c":"Asociación Todos Unidos Enfermedades Raras Uruguay","Website__c":"https://atueru.org.uy/"},{"Account_Name__c":"Fundación Lautaro te Necesita","Website__c":"https://fundacionlautarotenecesita.org/"},{"Account_Name__c":"United Leukodystrophy Foundation","Website__c":"https://ulf.org/"},{"Account_Name__c":"MLD Foundation","Website__c":"https://mldfoundation.org/"},{"Account_Name__c":"Alex The Leukodystrophy Charity","Website__c":"https://www.alextlc.org"},{"Account_Name__c":"Cure MLD","Website__c":"https://www.curemld.com"},{"Account_Name__c":"Metachromatic Leukodystrophy Natural History Study","Website__c":"https://www.chop.edu/research/metachromatic-leukodystrophy-mld-research"},{"Account_Name__c":"Hunter's Hope Foundation","Website__c":"https://www.huntershope.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":"Psychiatry","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":"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":"Lysosomal","Tag_Category__c":"Account;Cause;Disease Category","category_description":"Lysosomal storage diseases are a group of genetic metabolic diseases that affect the ability of the body's cells to break down substances and remove toxins.","curated_tag_name":"Lysosomal storage diseases"},{"Tag_Name__c":"Peripheral Neuropathy","Tag_Category__c":"Account","curated_tag_name":"Peripheral neuropathy"},{"Tag_Name__c":"Epilepsy","Tag_Category__c":"Account;Specialist","curated_tag_name":"Epilepsy"},{"Tag_Name__c":"Neuro-Ophthalmology","Tag_Category__c":"Specialist","curated_tag_name":"Neuro-ophthalmic diseases"},{"Tag_Name__c":"Neuromuscular medicine","Tag_Category__c":"Specialist","curated_tag_name":"Neuromuscular medicine"},{"Tag_Name__c":"Pediatrics","Tag_Category__c":"Specialist"}],"Age_At_Onset__c":[{"Age_At_Onset__c":"Adolescent","Provided_By__c":"ORPHA:512"},{"Age_At_Onset__c":"Childhood","Provided_By__c":"ORPHA:512"},{"Age_At_Onset__c":"Adult","Provided_By__c":"ORPHA:512"},{"Age_At_Onset__c":"Infancy","Provided_By__c":"ORPHA:512"}],"Diagnosis__c":[{"Type__c":"GTR","Curie__c":"MEDGEN:C0023522"},{"Type__c":"GTR","Curie__c":"MEDGEN:C0751276"},{"Type__c":"GTR","Curie__c":"MEDGEN:C2713319"}],"External_Identifier_Disease__c":[{"URL__c":"https://www.ncbi.nlm.nih.gov/books/NBK1130","Source__c":"Gene Review","Xref__c":"NBK1130"},{"URL__c":"https://browser.ihtsdotools.org/?perspective=full&conceptId1=66521008","Source__c":"MONDO:0018868","Xref__c":"66521008"},{"URL__c":"https://www.ncbi.nlm.nih.gov/medgen/?term=6071","Source__c":"C0023522","Xref__c":"MEDGEN:6071"},{"URL__c":"https://evsexplore.semantics.cancer.gov/evsexplore/concept/ncit/C61251","Source__c":"C0023522; MONDO:0018868","Xref__c":"C61251"},{"URL__c":"https://browser.ihtsdotools.org/?perspective=full&conceptId1=396338004","Source__c":"C0023522; MONDO:0018868","Xref__c":"396338004"},{"URL__c":"https://www.ebi.ac.uk/ols4/ontologies/doid/classes?obo_id=DOID%3A10581","Source__c":"MONDO:0018868","Xref__c":"DOID:10581"},{"URL__c":"https://www.orpha.net/en/disease/detail/512","Source__c":"C0023522; MONDO:0018868; ORPHA:512","Xref__c":"ORPHA:512"},{"URL__c":"https://browser.ihtsdotools.org/?perspective=full&conceptId1=238031009","Source__c":"MONDO:0018868","Xref__c":"238031009"},{"URL__c":"https://uts.nlm.nih.gov/uts/umls/concept/C0023522","Source__c":"C0023522","Xref__c":"C0023522"},{"URL__c":"https://www.ncbi.nlm.nih.gov/mesh/C007966","Source__c":"C0023522; MONDO:0018868","Xref__c":"D007966"},{"URL__c":"http://purl.obolibrary.org/obo/MONDO_0018868","Source__c":"GARD:0003230","Xref__c":"MONDO:0018868"},{"URL__c":"https://medlineplus.gov/genetics/condition/metachromatic-leukodystrophy","Source__c":"GARD:0003230","Xref__c":"https://medlineplus.gov/genetics/condition/metachromatic-leukodystrophy"},{"URL__c":"http://purl.bioontology.org/ontology/ICD10CM/E75.25","Source__c":"MONDO:0018868","Xref__c":"E75.25"},{"URL__c":"https://secure.ssa.gov/apps10/poms.nsf/lnx/0423022235","Xref__c":"423022235"}],"GARD_Disease_Gene__c":[{"GeneSymbol__c":"ARSA","GHR_URL__c":"https://medlineplus.gov/genetics/gene/arsa","Gene_Type__c":"protein-coding gene","Causal_Gene__c":true}],"Inheritance__c":["Autosomal recessive"],"GARD_Disease_Feature__c":[{"Provided_By__c":"ORPHA:512","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Floppiness/hypotonia is defined as reduced resistance to passive movement of joints. Physical examination of floppy/hypotonic infants shows head lag, lack of shoulder and elbow muscle contraction on traction response, inability to tighten the shoulder girdle muscles (or slipping through) when held under the axillae, scarf sign (when the arm is pulled to the opposite side, the arm wraps around the neck with the elbow crossing midline), hyperdorsiflexion of the feet, easy apposition of the thumb against the forearm, feet touching the cheek with ease and without discomfort, frog leg position, and inverted U sign on ventral suspension (head, arms, and legs hanging down without elbow or knee flexion and the trunk rounded in a dome shape).","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0008947","HPO_Synonym__c":"Decreased muscle tone in infant; Hypotonia early; Hypotonia in infancy; Hypotonia, early; Infantile hypotonia; Infantile muscular hypotonia","HPO_Name__c":"Floppy infant","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:512","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Partial or total incontinence of bowel or bladder.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0031064","HPO_Name__c":"Impaired continence","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:512","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"A condition characterized by changes in personality and thought patterns, often accompanied by hallucinations and delusional beliefs, is known as psychosis.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000709","HPO_Synonym__c":"Psychosis","HPO_Name__c":"Psychosis","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:512","HPO_Frequency__c":"Uncommon (<1-4%)","Feature__r":{"HPO_Description__c":"The presence of a neoplasm of the gallbladder.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0100575","HPO_Name__c":"Neoplasm of the gallbladder","Feature_System__c":"Digestive System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:512","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0011968","HPO_Synonym__c":"Decreased oral intake; Feeding difficulties; Feeding problems; Poor feeding","HPO_Name__c":"Feeding difficulties","Feature_System__c":"Digestive System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:512","HPO_Frequency__c":"Uncommon (<1-4%)","Feature__r":{"HPO_Description__c":"Bleeding into the biliary tree.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0100762","HPO_Synonym__c":"Haemobilia","HPO_Name__c":"Hemobilia","Feature_System__c":"Digestive System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:512","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Loss of the ability to control the urinary bladder leading to involuntary urination.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000020","HPO_Synonym__c":"Bladder incontinence; Loss of bladder control","HPO_Name__c":"Urinary incontinence","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:512","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Increased concentration of protein in the cerebrospinal fluid.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002922","HPO_Synonym__c":"Cerebrospinal fluid protein increased; Cerebrospinal fluid with increased protein; Elevated cerebrospinal fluid protein; Elevated csf protein; Hyperproteinorrhachia; Increased CSF protein; Increased protein in csf; Spinal fluid protein elevated","HPO_Name__c":"Increased CSF protein concentration","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"ORPHA:512","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"A mental disorder characterized by a disintegration of thought processes and emotional responsiveness. It most commonly manifests as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking. It is accompanied by significant social or occupational dysfunction. The onset of symptoms typically occurs in young adulthood, with a global lifetime prevalence of about 1%. This term is not a helpful parent term to describe abnormal experiences.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0100753","HPO_Name__c":"Schizophrenia","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:512","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"An anomaly of visually evoked potentials (VEP), which are electrical potentials, initiated by brief visual stimuli, which are recorded from the scalp overlying the visual cortex.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000649","HPO_Synonym__c":"Abnormal vision evoked potentials; Abnormal visual evoked potential; Abnormal visual evoked responses; Abnormal visual-evoked potentials; VEP abnormalities","HPO_Name__c":"Abnormality of visual evoked potentials","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:512","HPO_Frequency__c":"Occasional (5-29%)","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:512","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Periventricular leukomalacia is characterized by diffuse injury of deep cerebral white matter, accompanied in its most severe form by focal necrosis. The neuropathologic hallmarks of PVL are microglial activation and focal and diffuse periventricular depletion of premyelinating oligodendroglia.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0006970","HPO_Synonym__c":"PVL","HPO_Name__c":"Periventricular leukomalacia","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:512","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Feeding problem necessitating gastrostomy tube feeding.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0011471","HPO_Name__c":"Gastrostomy tube feeding in infancy","Feature_System__c":"Digestive System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:512","HPO_Frequency__c":"Uncommon (<1-4%)","Feature__r":{"HPO_Description__c":"An abnormality of the duodenum, i.e., the first section of the small intestine.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002246","HPO_Synonym__c":"Abnormality of the duodenum","HPO_Name__c":"Abnormal duodenum morphology","Feature_System__c":"Digestive System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:512","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"A deficit in coordination of muscle movements. Coordination is defined as the orchestrated movement of multiple body parts as required to accomplish intended actions, like walking.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002311","HPO_Synonym__c":"Difficulties in coordination; Incoordination; Incoordination of limb movements; Limb incoordination; Poor coordination; Poor motor coordination","HPO_Name__c":"Incoordination","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:512","HPO_Frequency__c":"Uncommon (<1-4%)","Feature__r":{"HPO_Description__c":"A structural anomaly of the gallbladder.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0012437","HPO_Synonym__c":"Abnormal gallbladder structure; Abnormal shape of gallbladder","HPO_Name__c":"Abnormal gallbladder morphology","Feature_System__c":"Digestive System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:512","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:512","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Peripheral neuropathy is a general term for any disorder of the peripheral nervous system. The main clinical features used to classify peripheral neuropathy are distribution, type (mainly demyelinating versus mainly axonal), duration, and course.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0009830","HPO_Synonym__c":"Peripheral nerve damage; Peripheral neuritis","HPO_Name__c":"Peripheral neuropathy","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:512","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Concentration or activity of an enzyme is above or below the limits of normal in the blood circulation.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0012379","HPO_Name__c":"Abnormal circulating enzyme concentration or activity","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"ORPHA:512","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"A loss of global cognitive ability of sufficient amount to interfere with normal social or occupational function. 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A person can become addicted or compulsively engaged with anything.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0030858","HPO_Name__c":"Addictive behavior","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:512","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:512","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Reduced strength of muscles.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001324","HPO_Synonym__c":"Muscle weakness; Muscular weakness","HPO_Name__c":"Muscle weakness","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:512","HPO_Frequency__c":"Frequent (30-79%)","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:512","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:512","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Sudden and involuntary contractions of one or more muscles.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0003394","HPO_Synonym__c":"Muscle cramps; Muscle spasms","HPO_Name__c":"Muscle spasm","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:512","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0012531","HPO_Synonym__c":"Pain","HPO_Name__c":"Pain","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:512","HPO_Frequency__c":"Uncommon (<1-4%)","Feature__r":{"HPO_Description__c":"An abnormality of the stomach.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002577","HPO_Synonym__c":"Abnormality of the stomach","HPO_Name__c":"Abnormal stomach morphology","Feature_System__c":"Digestive System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:512","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"An unintentional, oscillating to-and-fro muscle movement about a joint axis.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001337","HPO_Synonym__c":"Tremor; Tremors","HPO_Name__c":"Tremor","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:512","HPO_Frequency__c":"Occasional (5-29%)","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:512","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002359","HPO_Synonym__c":"Frequent falls","HPO_Name__c":"Frequent falls","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:512","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:512","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"An abnormal shift in patterns of thinking, acting, or feeling.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000751","HPO_Synonym__c":"Personality change; Personality changes","HPO_Name__c":"Personality changes","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:512","HPO_Frequency__c":"Uncommon (<1-4%)","Feature__r":{"HPO_Description__c":"A type of rigidity that is manifested by an exaggerated extensor posture of all extremities.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0025013","HPO_Synonym__c":"Decerebrate posturing","HPO_Name__c":"Decerebrate rigidity","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:512","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Atypical behavior is an abnormality in a person's actions that can be controlled or modulated by the will of the individual. While abnormal behaviors can be difficult to control, they are distinct from other abnormal actions that cannot be affected by the individual's will.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000708","HPO_Synonym__c":"Behavioral abnormality; Behavioral changes; Behavioral disorders; Behavioral disturbances; Behavioral problems; Behavioral symptoms; Behavioral/psychiatric abnormalities; Behavioural symptoms; Behavioural/Psychiatric abnormality; Psychiatric disorders; Psychiatric disturbances","HPO_Name__c":"Atypical behavior","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:512","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":"ORPHA:512","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Reduction of neurologic reflexes such as the knee-jerk reaction.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001265","HPO_Synonym__c":"Decreased reflex response; Decreased reflexes","HPO_Name__c":"Hyporeflexia","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:512","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Involuntary fecal soiling in adults and children who have usually already been toilet trained.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002607","HPO_Synonym__c":"Anal incontinence; Fecal incontinence; Loss of bowel control","HPO_Name__c":"Bowel incontinence","Feature_System__c":"Digestive System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:512","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"An abnormal gait pattern characterized by the failure of the heel to contact the floor at the onset of stance during gait.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0030051","HPO_Synonym__c":"Tiptoe gait; Toe walking; Walking on tiptoes","HPO_Name__c":"Tip-toe gait","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:512","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"A reduction in the speed at which electrical signals propagate along the axon of a neuron.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000762","HPO_Synonym__c":"Decreased NCV; Decreased nerve conduction velocities; Delayed nerve conduction velocity; Reduced nerve conduction velocities; Slow nerve conduction velocity; Slowed nerve conduction velocities","HPO_Name__c":"Decreased nerve conduction velocity","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Procedure_NCV"}},{"Provided_By__c":"ORPHA:512","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"A decreased magnitude of the sensory perception of sound.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000365","HPO_Synonym__c":"Deafness; Hearing defect; Hearing impairment; Hypacusis","HPO_Name__c":"Hearing impairment","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:512","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Chronic pain in the limbs with no clear focal etiology.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0009763","HPO_Synonym__c":"Limb pain","HPO_Name__c":"Limb pain","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}}],"tags":{"Cause":["Genetics","Inborn Errors of Metabolism","Leukodystrophy","Lysosomal"],"Disease Category":["Genetics","Neurology","Inborn Errors of Metabolism","Leukodystrophy","Lysosomal"],"Specialist":["Genetics","Neurology","Ophthalmology","Psychiatry","Epilepsy","Neuro-Ophthalmology","Neuromuscular medicine","Pediatrics"],"Account":["Leukodystrophy","Lysosomal","Peripheral Neuropathy","Epilepsy"]},"synonyms":["arsa deficiency"," arylsulfatase a deficiency"," cerebral sclerosis diffuse metachromatic form"," cerebroside sulfatase deficiency"," deficiency of cerebroside-sulfatase"," familial progressive cerebral sclerosis"," metachromatic leucodystrophy"," metachromatic leukoencephalopathy"," metachromatic leukoencephaly"," mld"," mld - metachromatic leucodystrophy"," scholz cerebral sclerosis"," sulfatide lipidosis"," sulfatide lipoidosis"," van bogaert-nijssen disease"],"spanishId":12627,"spanishName":"leucodistrofia-metacromatica"}