{"Name":"Holocarboxylase synthetase deficiency","DiseaseID__c":"GARD:0002721","id":2721,"encodedName":"holocarboxylase-synthetase-deficiency","IsDeleted":false,"Disease_Name_Full__c":"Holocarboxylase synthetase deficiency","Xref_IDs__c":"15307001; 360369003; C0268581; C98842; D028922; DOID:859; MEDGEN:120653; MONDO:0009666; OMIM:253270; ORPHA:79242","USA_Estimate__c":"5,000","No_of_Specialist_Tagsa__c":2,"No_of_ClinGen_records__c":0,"No_of_GeneReviews__c":0,"No_of_HHS_records__c":1,"World_Estimate__c":"8,000 to 80,000","No_of_HRSA_records__c":0,"Evidence_Based_Score__c":1,"No_of_Disease_Descriptions__c":3,"Disease_Characteristics_Score__c":7,"No_of_Age_at_Onset__c":3,"Description_Source__c":"MONDO:0009666","Disease_Description__c":"A rare, early-onset and life-threatening, multiple carboxylase deficiency that when left untreated, is characterized by vomiting, tachypnea, irritability, lethargy, exfoliative dermatitis, and seizures that can worsen to coma and death.","GARD_Name__c":"Holocarboxylase synthetase deficiency","GARD_Synonym__c":"biotin-(propionyl-coa-carboxylase) ligase deficiency; early-onset multiple carboxylase deficiency; holocarboxylase synthase deficiency; multiple carboxylase deficiency - neonatal onset; multiple carboxylase deficiency, early onset; neonatal multiple carboxylase deficiency","Curated_Disease_Description_Source__c":"MONDO:0009666","Curated_Disease_Description__c":"Holocarboxylase synthetase deficiency is an inherited disorder in which the body is unable to use the vitamin biotin effectively. This disorder is classified as a multiple carboxylase deficiency, which is a group of disorders characterized by impaired activity of certain enzymes that depend on biotin. The signs and symptoms of holocarboxylase synthetase deficiency typically appear within the first few months of life, but the age of onset varies. Affected infants often have difficulty feeding, breathing problems, a skin rash, hair loss (alopecia), and a lack of energy (lethargy). Immediate treatment and lifelong management with biotin supplements may prevent many of these complications. If left untreated, the disorder can lead to delayed development, seizures, and coma. These medical problems may be life-threatening in some cases.","Curated_USA_Estimate_Source__c":null,"Curated_USA_Estimate__c":"5,000","Age_at_Onset_Snippet_Text__c":"from Birth to Childhood","SourceID__c":"ORPHA:79242","Deprecated__c":"No","Disease_Concept_Type__c":"Rare Disease Entity","MONDO_ID__c":"MONDO:0009666","ORPHANET_ID__c":"ORPHA:79242","Replaced_By_ID__c":null,"Display_Spanish_Disease_Name__c":"Deficiencia de holocarboxilasa sintetasa","Spanish_Description_Source__c":"ORPHA:79242","Spanish_Description__c":"Es una deficiencia múltiple de carboxilasas, de inicio temprano y potencialmente mortal, poco frecuente, que en ausencia de tratamiento se caracteriza por vómitos, taquipnea, irritabilidad, letargia, dermatitis exfoliativa, y crisis epilépticas que pueden empeorar hasta el coma y el fallecimiento.","Spanish_Disease_Name__c":"deficiencia de holocarboxilasa sintetasa","Spanish_GARD_Synonym__c":"deficiencia múltiple de carboxilasas de inicio precoz; deficiencia múltiple de carboxilasas neonatal","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":"Holocarboxylase synthetase deficiency is an inherited disorder in which the body is unable to use the vitamin biotin effectively. This disorder is classified as a multiple carboxylase deficiency, which is a group of disorders characterized by impaired activity of certain enzymes that depend on biotin. The signs and symptoms of holocarboxylase synthetase deficiency typically appear within the first few months of life, but the age of onset varies. Affected infants often have difficulty feeding, breathing problems, a skin rash, hair loss (alopecia), and a lack of energy (lethargy). Immediate treatment and lifelong management with biotin supplements may prevent many of these complications. If left untreated, the disorder can lead to delayed development, seizures, and coma. These medical problems may be life-threatening in some cases.","Curated_Disease_Description_Source__c":"MONDO:0009666","GARD_Synonym__c":"biotin-(propionyl-coa-carboxylase) ligase deficiency; early-onset multiple carboxylase deficiency; holocarboxylase synthase deficiency; multiple carboxylase deficiency - neonatal onset; multiple carboxylase deficiency, early onset; neonatal multiple carboxylase deficiency","Name":"Holocarboxylase synthetase deficiency","Curated_USA_Estimate__c":"5,000","estimateUsa":"5,000"}],"Organization_Supported_Diseases__c":[{"Account_Name__c":"Organic Acidemia Association","Website__c":"https://oaanews.org/"},{"Account_Name__c":"Metabolic Support UK","Website__c":"https://www.metabolicsupportuk.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":"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":"Pediatrics","Tag_Category__c":"Specialist"}],"Age_At_Onset__c":[{"Age_At_Onset__c":"Childhood","Provided_By__c":"ORPHA:79242"},{"Age_At_Onset__c":"Neonatal","Provided_By__c":"ORPHA:79242"},{"Age_At_Onset__c":"Infancy","Provided_By__c":"ORPHA:79242"}],"Diagnosis__c":[{"Type__c":"NEWBORN","Category__c":"Core","Curie__c":"http://newbornscreeningcodes.nlm.nih.gov/nb/sc/condition/MCD"},{"Type__c":"GTR","Curie__c":"MEDGEN:C0268581"}],"External_Identifier_Disease__c":[{"URL__c":"https://raresource.nih.gov/diseases/filter/0002721","Source__c":"RareSource"},{"URL__c":"https://www.ebi.ac.uk/ols4/ontologies/doid/classes?obo_id=DOID%3A859","Source__c":"MONDO:0009666","Xref__c":"DOID:859"},{"URL__c":"https://www.omim.org/entry/253270","Source__c":"C0268581; MONDO:0009666; ORPHA:79242","Xref__c":"OMIM:253270"},{"URL__c":"https://www.ncbi.nlm.nih.gov/medgen/?term=120653","Source__c":"C0268581","Xref__c":"MEDGEN:120653"},{"URL__c":"https://www.ncbi.nlm.nih.gov/mesh/C028922","Source__c":"C0268581; MONDO:0009666","Xref__c":"D028922"},{"URL__c":"https://browser.ihtsdotools.org/?perspective=full&conceptId1=360369003","Source__c":"C0268581; MONDO:0009666","Xref__c":"360369003"},{"URL__c":"https://www.orpha.net/en/disease/detail/79242","Source__c":"C0268581; MONDO:0009666; ORPHA:79242","Xref__c":"ORPHA:79242"},{"URL__c":"https://evsexplore.semantics.cancer.gov/evsexplore/concept/ncit/C98842","Source__c":"C0268581; MONDO:0009666","Xref__c":"C98842"},{"URL__c":"https://uts.nlm.nih.gov/uts/umls/concept/C0268581","Source__c":"C0268581","Xref__c":"C0268581"},{"URL__c":"https://browser.ihtsdotools.org/?perspective=full&conceptId1=15307001","Source__c":"MONDO:0009666","Xref__c":"15307001"},{"URL__c":"https://medlineplus.gov/genetics/condition/holocarboxylase-synthetase-deficiency","Source__c":"GARD:0002721","Xref__c":"https://medlineplus.gov/genetics/condition/holocarboxylase-synthetase-deficiency"},{"URL__c":"http://purl.obolibrary.org/obo/MONDO_0009666","Source__c":"GARD:0002721","Xref__c":"MONDO:0009666"},{"URL__c":"https://evsexplore.semantics.cancer.gov/evsexplore/concept/ncit/C99247","Source__c":"C0268581","Xref__c":"C99247"}],"GARD_Disease_Gene__c":[{"GeneSymbol__c":"HLCS","GHR_URL__c":"https://medlineplus.gov/genetics/gene/hlcs","Gene_Type__c":"protein-coding gene","Causal_Gene__c":true}],"Inheritance__c":["Autosomal recessive"],"GARD_Disease_Feature__c":[{"Provided_By__c":"ORPHA:79242","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"An increased concentration of ammonia in the blood.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001987","HPO_Synonym__c":"High blood ammonia levels","HPO_Name__c":"Hyperammonemia","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"ORPHA:79242","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"A type of eczema that occurs in the lips and perioral area.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0011127","HPO_Synonym__c":"Eczema around the mouth","HPO_Name__c":"Perioral eczema","Feature_System__c":"Skin System; Immune System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:79242","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Excretion of non-amino organic acids in urine.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001992","HPO_Name__c":"Organic aciduria","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"ORPHA:79242","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"A reduction in the number of circulating thrombocytes.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001873","HPO_Synonym__c":"Low platelet count","HPO_Name__c":"Thrombocytopenia","Feature_System__c":"Blood and Blood-Forming Tissue","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:79242","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"A deficiency or slowing down of growth pre- and postnatally.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001510","HPO_Synonym__c":"Delayed growth; Growth deficiency; Growth delay; Growth failure; Growth retardation; Poor growth; Retarded growth","HPO_Name__c":"Growth delay","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:79242","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Reduction of total body weight.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001824","HPO_Synonym__c":"Loss of weight","HPO_Name__c":"Weight loss","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:79242","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Inflammation of the cornea and conjunctiva.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001096","HPO_Name__c":"Keratoconjunctivitis","Feature_System__c":"Cardiovascular System; Immune System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:79242","HPO_Frequency__c":"Very frequent (80-99%)","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:79242","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001252","HPO_Synonym__c":"Low muscle tone; Low or weak muscle tone; Muscle hypotonia; Muscular hypotonia","HPO_Name__c":"Hypotonia","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:79242","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"The complete absence of wakefulness and consciousness, which is evident through a lack of response to any form of external stimuli.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001259","HPO_Synonym__c":"Coma; Persistent vegetative state; Stupor; Unconsciousness","HPO_Name__c":"Coma","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:79242","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Eczema is a form of dermatitis that is characterized by scaly, pruritic, erythematous lesions located on flexural surfaces.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000964","HPO_Synonym__c":"Eczema","HPO_Name__c":"Eczematoid dermatitis","Feature_System__c":"Skin System; Immune System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:79242","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0007549","HPO_Name__c":"Desquamation of skin soon after birth","Feature_System__c":"Skin System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:79242","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"A noncongenital process of hair loss, which may progress to partial or complete baldness.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001596","HPO_Synonym__c":"Hair loss","HPO_Name__c":"Alopecia","Feature_System__c":"Skin System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:79242","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"A state of fatigue, either physical or mental slowness and sluggishness, with difficulties in initiating or performing simple tasks. Distinguished from apathy which implies indifference and a lack of desire or interest in the task. A person with lethargy may have the desire, but not the energy to engage in personal or socially relevant tasks.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001254","HPO_Synonym__c":"Dullness; Inaction; Inactivity; Languor; Lethargy; Slowness; Torpor","HPO_Name__c":"Lethargy","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:79242","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Lack of desire to eat (loss of appetite).","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002039","HPO_Synonym__c":"Anorexia; Deliberately not eating; Obsessive dieting; Refusing to eat","HPO_Name__c":"Anorexia","Feature_System__c":"Digestive System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:79242","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"An emotional state characterized by negative feelings of heightened frustration, annoyance, or feeling upset, often triggered by internal factors (e.g., fatigue, hunger, unfulfilled desires) or external factors (e.g., social or environmental challenges). Irritability may be unpredictable, and is accompanied by a lowered threshold for emotional reactivity and observable features (speech, facial expressions, or psychomotor activity).","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000737","HPO_Synonym__c":"Cranky; Easily annoyed; Easily bothered; Easily upset; Grumpy; Hot-temper; Irritability; Irritable; Irritable mood; On edge; Quick-temper; Short fuse; Short tempered","HPO_Name__c":"Irritability","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:79242","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Respiratory distress is objectively observable as the physical or emotional consequences from the experience of dyspnea. The physical presentation of respiratory distress is generally referred to as labored breathing, while the sensation of respiratory distress is called shortness of breath or dyspnea.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002098","HPO_Synonym__c":"Breathing difficulties; Labored breathing; Respiratory difficulties","HPO_Name__c":"Respiratory distress","Feature_System__c":"Respiratory system","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:79242","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Very rapid breathing.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002789","HPO_Synonym__c":"Increased respiratory rate or depth of breathing; Polypnea","HPO_Name__c":"Tachypnea","Feature_System__c":"Respiratory system","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:79242","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Nausea is a commonly encountered symptom that has been defined as an unpleasant painless subjective feeling that one will imminently vomit. Vomiting has been defined as the forceful expulsion of the contents of the stomach, duodenum, or jejunum through the oral cavity. While nausea and vomiting are often thought to exist on a temporal continuum, this is not always the case. There are situations when severe nausea may be present without emesis and less frequently, when emesis may be present without preceding nausea.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002017","HPO_Synonym__c":"Nausea and vomiting","HPO_Name__c":"Nausea and vomiting","Feature_System__c":"Digestive System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:79242","HPO_Frequency__c":"Occasional (5-29%)","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"}}],"tags":{"Cause":["Genetics","Inborn Errors of Metabolism"],"Disease Category":["Genetics","Inborn Errors of Metabolism"],"Specialist":["Genetics","Pediatrics"]},"synonyms":["biotin-(propionyl-coa-carboxylase) ligase deficiency"," early-onset multiple carboxylase deficiency"," holocarboxylase synthase deficiency"," multiple carboxylase deficiency - neonatal onset"," multiple carboxylase deficiency, early onset"," neonatal multiple carboxylase deficiency"]}