{"orpha":436,"name":"Hypophosphatasia","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["HPP","Phosphoethanolaminuria","Rathbun disease"],"definition":"A rare, genetic metabolic disorder characterized by reduced activity of unfractionated serum alkaline phosphatase (ALP) and various symptoms from life-threatening, severely impaired mineralization at birth to musculo-skeletal pain in adulthood.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-436/","orphanet_url":"https://www.orpha.net/en/disease/detail/436","names":{"fr":{"name":"Hypophosphatasie","synonyms":["HPP","Maladie de Rathbun","Phosphoéthanolaminurie"],"definition":"Maladie métabolique rare d'origine héréditaire caractérisée par une réduction de l'activité de la phosphatase alcaline sérique (PA) et par divers symptômes allant d'une altération sévère de la minéralisation à la naissance à des douleurs musculo-squelettiques à l'âge adulte."},"de":{"name":"Hypophosphatasie","synonyms":["HPP","Phosphoethanolaminurie","Rathbun-Syndrom"],"definition":"Eine seltene, genetisch bedingte Stoffwechselstörung, die durch eine verminderte Aktivität der unfraktionierten alkalischen Phosphatase (ALP) im Serum gekennzeichnet ist. Die klinische Ausprägung ist variabel und kann von einer schweren, möglicherweise lebensbedrohlichen stark beeinträchtigten Mineralisierung der Knochen bei der Geburt bis hin zu Muskel- und Skelettschmerzen im Erwachsenenalter reichen."},"es":{"name":"Hipofosfatasia","synonyms":["Enfermedad de Rathburn","Fosfoetanolaminuria","HPP"],"definition":"Es un trastorno metabólico de origen genético, poco frecuente, caracterizado por la reducción de la actividad de la fosfatasa alcalina no fraccionada sérica (FA) y por síntomas que varían desde una grave afectación de la mineralización al nacimiento, potencialmente mortal hasta dolor musculoesquelético en la edad adulta."},"it":{"name":"Ipofosfatasia","synonyms":["Fosfoetanolaminuria","HPP","Malattia di Rathburn"],"definition":"Si tratta di una malattia metabolica genetica rara, caratterizzata dalla riduzione dell'attività della fosfatasi alcalina (ALP) sierica non frazionata e da altri sintomi, che vanno dalla compromissione congenita grave, potenzialmente letale, della mineralizzazione, al dolore muscoloscheletrico nell'età adulta."},"nl":{"name":"Hypofosfatasie","synonyms":["Fosfo-ethanolaminurie","HPP","Ziekte van Rathbun"],"definition":"Een zeldzame, genetische metabole aandoening, gekarakteriseerd door verminderde activiteit van alkaline fosfatase (ALP) in niet-gefractioneerd serum en verschillende symptomen, gaande van levensbedreigende, ernstig verstoorde mineralisatie bij de geboorte tot musculoskeletale pijn in de volwassenheid."},"pt":{"name":"Hipofosfatasia","synonyms":["Doença de Rathburn","Fosfoetanolaminúria"],"definition":"Doença metabólica e genética rara caracterizado por atividade reduzida da fosfatase alcalina (ALP) não fracionada sérica e vários sintomas, desde uma grave diminuição da mineralização óssea com risco de vida ao nascimento, à dor musculoesquelética na idade adulta."},"pl":{"name":"Hipofosfatazja","synonyms":["Choroba Rathburna","Fosfoetanololaminuria","HPP"],"definition":"Rzadkie, genetycznie uwarunkowane zaburzenie metaboliczne charakteryzujące się zmniejszoną aktywnością niefrakcjonowanej fosfatazy alkalicznej w surowicy i różnymi związanymi z tym objawami, od zagrażającej życiu poważnie upośledzonej mineralizacji stwierdzanej już po urodzeniu, po bóle z układu mięśniowo-szkieletowego w wieku dorosłym."},"cs":{"name":"Hypofosfatázie","synonyms":["HPP","Fosfoetanolaminurie","Rathburnova choroba"]},"uk":{"name":"Гіпофосфатазія","synonyms":["HPP","Фосфоетаноламінурія","Хвороба Ратбуна"],"definition":"A rare, genetic metabolic disorder characterized by reduced activity of unfractionated serum alkaline phosphatase (ALP) and various symptoms from life-threatening, severely impaired mineralization at birth to musculo-skeletal pain in adulthood."},"zh":{"name":"低磷酸酯酶症","synonyms":["磷酸乙醇胺尿症"]},"tr":{"name":"Hipofosfatazya","synonyms":["HPP","Rathbun hastalığı","Fosfoetanolaminüri"]}},"xrefs":[{"source":"OMIM","code":"146300","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"241500","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"241510","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E83.3","qualifier":"NTBT","icd_relation":"inclusion","validated":true},{"source":"ICD-11","code":"5C64.3","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"422012968"},{"source":"MONDO","code":"0018570","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"D007014","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C0020630","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"6734","qualifier":"E","icd_relation":null,"validated":true},{"source":"MedDRA","code":"10049933","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":93419,"name":"Rare bone disease"},"parents":[{"orpha":139009,"name":"Developmental anomaly of metabolic origin","classifications":[147,156]},{"orpha":93447,"name":"Primary bone dysplasia with defective bone mineralization","classifications":[147,156,199]}],"children":[{"orpha":247676,"name":"Adult hypophosphatasia","type":"Clinical subtype"},{"orpha":247667,"name":"Childhood-onset hypophosphatasia","type":"Clinical subtype"},{"orpha":247651,"name":"Infantile hypophosphatasia","type":"Clinical subtype"},{"orpha":247685,"name":"Odontohypophosphatasia","type":"Clinical subtype"},{"orpha":247623,"name":"Perinatal lethal hypophosphatasia","type":"Clinical subtype"},{"orpha":247638,"name":"Prenatal benign hypophosphatasia","type":"Clinical subtype"}],"genes":[],"genes_via_subtypes":[{"symbol":"ALPL","name":"alkaline phosphatase, biomineralization associated","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"10737975[PMID]_17916236[PMID]_20301329[PMID]","hgnc":"438","ensembl":"ENSG00000162551","omim":"171760","loci":["1p36.12"],"via":{"orpha":247623,"name":"Perinatal lethal hypophosphatasia"}},{"symbol":"ALPL","name":"alkaline phosphatase, biomineralization associated","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"10737975[PMID]_17916236[PMID]_20301329[PMID]","hgnc":"438","ensembl":"ENSG00000162551","omim":"171760","loci":["1p36.12"],"via":{"orpha":247638,"name":"Prenatal benign hypophosphatasia"}},{"symbol":"ALPL","name":"alkaline phosphatase, biomineralization associated","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"10737975[PMID]_17916236[PMID]_20301329[PMID]","hgnc":"438","ensembl":"ENSG00000162551","omim":"171760","loci":["1p36.12"],"via":{"orpha":247651,"name":"Infantile hypophosphatasia"}},{"symbol":"ALPL","name":"alkaline phosphatase, biomineralization associated","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"10737975[PMID]_17916236[PMID]_20301329[PMID]","hgnc":"438","ensembl":"ENSG00000162551","omim":"171760","loci":["1p36.12"],"via":{"orpha":247667,"name":"Childhood-onset hypophosphatasia"}},{"symbol":"ALPL","name":"alkaline phosphatase, biomineralization associated","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"10737975[PMID]_17916236[PMID]_20301329[PMID]","hgnc":"438","ensembl":"ENSG00000162551","omim":"171760","loci":["1p36.12"],"via":{"orpha":247676,"name":"Adult hypophosphatasia"}},{"symbol":"ALPL","name":"alkaline phosphatase, biomineralization associated","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"10737975[PMID]_17916236[PMID]_20301329[PMID]","hgnc":"438","ensembl":"ENSG00000162551","omim":"171760","loci":["1p36.12"],"via":{"orpha":247685,"name":"Odontohypophosphatasia"}}],"inheritance":["Autosomal dominant","Autosomal recessive"],"onset":["All ages"],"prevalence":[{"type":"Point prevalence","qualification":"Class only","class":"Unknown","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_[EXPERT]_21488855[PMID]"},{"type":"Point prevalence","qualification":"Value and class","class":"<1 / 1 000 000","value":0.0208,"area":"China","status":"Validated","source":"34103049[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2026-03-16","source":"37982857[PMID]_40047955[PMID]_37249457[PMID]_20301329[PMID]","terms":[{"hpo":"HP:0000944","label":"Abnormal metaphysis morphology","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000772","label":"Abnormal rib morphology","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000164","label":"Abnormality of the dentition","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0003282","label":"Decreased circulating alkaline phosphatase activity","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002097","label":"Emphysema","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0008872","label":"Feeding difficulties in infancy","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000239","label":"Large fontanelles","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000774","label":"Narrow chest","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002653","label":"Bone pain","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000934","label":"Chondrocalcinosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012532","label":"Chronic pain","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001363","label":"Craniosynostosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0032537","label":"Delayed fracture healing","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0032477","label":"Elevated circulating vitamin B6 concentration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003491","label":"Elevated urine pyrophosphate","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001531","label":"Failure to thrive in infancy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012378","label":"Fatigue","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001288","label":"Gait disturbance","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001510","label":"Growth delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003072","label":"Hypercalcemia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001252","label":"Hypotonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002659","label":"Increased susceptibility to fractures","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0041162","label":"Metatarsal fracture","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001270","label":"Motor delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002756","label":"Pathologic fracture","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003239","label":"Phosphoethanolaminuria","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0006323","label":"Premature loss of primary teeth","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0100036","label":"Pseudo-fractures","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002757","label":"Recurrent fractures","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002748","label":"Rickets","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0004322","label":"Short stature","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002360","label":"Sleep abnormality","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0006487","label":"Bowing of the long bones","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000670","label":"Carious teeth","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002150","label":"Hypercalciuria","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002516","label":"Increased intracranial pressure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000737","label":"Irritability","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001324","label":"Muscle weakness","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000121","label":"Nephrocalcinosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000787","label":"Nephrolithiasis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002749","label":"Osteomalacia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002093","label":"Respiratory insufficiency","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010781","label":"Skin dimple","frequency":"Occasional (29-5%)","criteria":null}]}}