{"orpha":505248,"name":"Mucopolysaccharidosis-like syndrome with congenital heart defects and hematopoietic disorders","type":"Malformation syndrome","group":"Disorder","status":"active","flags":[],"synonyms":["Mucopolysaccharidosis-like plus disease"],"definition":"A rare genetic disease characterized by early-onset respiratory difficulties and frequent respiratory infections, congenital heart defects, dysostosis multiplex, hepatosplenomegaly, renal involvement, hematopoietic abnormalities, facial dysmorphism (coarse facial features, large forehead, synophrys, long eyelashes, broad nasal bridge, macroglossia, short neck, and low hairline), and global developmental delay. Laboratory examination shows increased urinary excretion of glycosaminoglycans and increased plasma heparan sulfate, but no lysosomal enzyme deficiency. The disease is usually fatal in the first years of life.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-505248/","orphanet_url":"https://www.orpha.net/en/disease/detail/505248","names":{"fr":{"name":"Mucopolysaccharidose-like avec cardiopathie congénitale et atteintes hématopoïétiques","definition":"Maladie génétique rare caractérisée par des difficultés respiratoires précoces et des infections respiratoires fréquentes, des malformations cardiaques congénitales, une dysostose multiplexe, une hépatosplénomégalie, une atteinte rénale, des anomalies hématopoïétiques, une dysmorphie faciale (traits grossiers du visage, grand front, synophridie, longs cils, large pont nasal, macroglossie, cou court, implantation basse des cheveux) et un retard global de développement. L'examen biologique révèle une excrétion urinaire accrue de glycosaminoglycanes et une augmentation de l'héparane sulfate plasmatique, mais pas de déficit enzymatique lysosomal. La maladie est généralement fatale dans les premières années de la vie."},"de":{"name":"Mukopolysaccharidose-ähnliches Syndrom mit kongenitalen Herzfehlern und hämatopoetischen Störungen","synonyms":["Mukopolysaccharidose plus-Krankheit"],"definition":"Eine seltene genetische Erkrankung, die durch früh einsetzende Atembeschwerden und häufige Atemwegsinfektionen, angeborene Herzfehler, Dysostosis multiplex, Hepatosplenomegalie, Nierenbeteiligung, hämatopoetische Anomalien, Gesichtsdysmorphien (grobe Gesichtsdysmorphien, große Stirn, Synophrys, lange Wimpern, breiter Nasenrücken, Makroglossie, kurzer Hals und niedriger Haaransatz) und eine globale Entwicklungsverzögerung gekennzeichnet ist. Die Laboruntersuchung zeigt eine erhöhte Ausscheidung von Glykosaminoglykanen im Urin und einen erhöhten Heparansulfatspiegel im Plasma, jedoch keinen Mangel an lysosomalen Enzymen. Die Erkrankung verläuft in der Regel in den ersten Lebensjahren tödlich."},"es":{"name":"Síndrome similar a mucopolisacaridosis con defectos cardíacos congénitos y trastornos hematopoyéticos","synonyms":["Enfermedad similar a mucopolisacaridosis plus"],"definition":"Es una enfermedad de base genética poco frecuente caracterizada por dificultades respiratorias e infecciones respiratorias frecuentes de inicio temprano, defectos cardíacos congénitos, disostosis múltiple, hepatoesplenomegalia, afectación renal, anomalías hematopoyéticas, dismorfia facial (rasgos faciales toscos, frente grande, sinofridia, pestañas largas, puente nasal ancho, macroglosia, cuello corto y línea de implantación del cabello baja) y retraso global del desarrollo. Las pruebas de laboratorio muestran un aumento de la excreción urinaria de glicosaminoglicanos y niveles elevados de heparán sulfato plasmático, aunque no muestran deficiencia de enzimas lisosomales. La enfermedad suele ser mortal en los primeros años de vida."},"it":{"name":"Sindrome simil-mucopolisaccaridosi con cardiopatie congenite e anomalie dell'ematopoiesi","definition":"Si tratta di una malattia genetica rara, caratterizzata da difficoltà respiratorie ad esordio precoce e infezioni respiratorie frequenti, cardiopatie congenite, disostosi multipla, epatosplenomegalia, interessamento renale, anomalie dell'ematopoiesi, dismorfismi facciali (aspetto grossolano del viso, fronte ampia, sinofria, ciglia lunghe, sella nasale larga, macroglossia, collo corto, bassa attaccatura dei capelli) e ritardo dello sviluppo globale. Gli esami di laboratorio evidenziano un aumento dei glicosaminoglicani nelle urine e dell'eparan solfato nel plasma, in assenza di deficit degli enzimi lisosomiali. Di solito la malattia è letale nei primi anni di vita."},"nl":{"name":"Mucopolysacharidose-achtig syndroom met congenitale hartdefecten en hematopoëtische stoornissen","synonyms":["Mucopolysacharidose-achtige plus-ziekte"],"definition":"Een zeldzame, genetische aandoening, gekarakteriseerd door vroeg aanvangende ademhalingsproblemen en frequente luchtweginfecties, congenitale hartdefecten, dysostosis multiplex, hepatosplenomegalie, betrokkenheid van nier, hematopoëtische afwijkingen, faciale dysmorfie (ruwe gelaatskenmerken, groot voorhoofd, synophrys, lange wimpers, brede neusbrug, macroglossie, korte nek, en lage haarlijn), en algehele ontwikkelingsachterstand. Laboratoriumonderzoek toont verhoogde excretie van glycosaminoglycanen in urine en verhoogd gehalte van heparansulfaat in plasma, maar geen lysosomale enzymdeficiëntie. De aandoening is meestal fataal in de eerste levensjaren."},"pt":{"name":"Síndrome mucopolissacaridose-like com defeitos cardíacos congénitos e doenças hematopoiéticas"},"pl":{"name":"Zespół podobny do mukopolisacharydoz z wadami wrodzonymi serca i zaburzeniami hematopoetycznymi","synonyms":["Mucopolysaccharidosis-like plus disease"]},"cs":{"name":"Syndrom podobný mukopolysacharidóze s vrozenými srdečními vadami a hematopoetickými poruchami","synonyms":["Nemoc podobná mukopolysacharidóze plus"]},"uk":{"name":"Мукополісахаридозоподібний синдром з вродженими вадами серця та порушеннями кровотворення","synonyms":["Хвороба, подібна до мукополісахаридозу плюс"],"definition":"A rare genetic disease characterized by early-onset respiratory difficulties and frequent respiratory infections, congenital heart defects, dysostosis multiplex, hepatosplenomegaly, renal involvement, hematopoietic abnormalities, facial dysmorphism (coarse facial features, large forehead, synophrys, long eyelashes, broad nasal bridge, macroglossia, short neck, and low hairline), and global developmental delay. Laboratory examination shows increased urinary excretion of glycosaminoglycans and increased plasma heparan sulfate, but no lysosomal enzyme deficiency. The disease is usually fatal in the first years of life."},"zh":{"name":"粘多糖病样综合征伴有先天性心脏缺陷和造血功能障碍","synonyms":["粘多糖病样附加性病变"]},"tr":{"name":"Doğumsal kalp defektleri ve hematopoetik bozukluklar ile seyreden mukopolisakkaridoz benzeri sendrom","synonyms":["Mukopolisakkaridoz benzeri artı hastalık"]}},"xrefs":[{"source":"OMIM","code":"617303","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"Q87.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"0015012","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C5568800","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":93890,"name":"Rare developmental defect during embryogenesis"},"parents":[{"orpha":93454,"name":"Dysostosis with predominant vertebral and costal involvement","classifications":[147,156,199]},{"orpha":611327,"name":"Genetic multiple congenital anomalies/dysmorphic syndrome-intellectual disability","classifications":[156]},{"orpha":102283,"name":"Multiple congenital anomalies/dysmorphic syndrome-intellectual disability","classifications":[147,181]},{"orpha":156610,"name":"Rare genetic respiratory disease","classifications":[156]},{"orpha":101944,"name":"Rare pulmonary disease","classifications":[184]}],"children":[],"genes":[{"symbol":"VPS33A","name":"VPS33A core subunit of CORVET and HOPS complexes","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"28013294[PMID]","hgnc":"18179","ensembl":"ENSG00000139719","omim":"610034","loci":["12q24.31"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Infancy"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":19.0,"area":"Worldwide","status":"Validated","source":"28013294[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_28013294[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2020-01-21","source":"31070736[PMID]_31936524[PMID]_28013294[PMID]","terms":[{"hpo":"HP:0002086","label":"Abnormality of the respiratory system","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001903","label":"Anemia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000280","label":"Coarse facial features","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000943","label":"Dysostosis multiplex","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001371","label":"Flexion contracture","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001433","label":"Hepatosplenomegaly","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000093","label":"Proteinuria","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002205","label":"Recurrent respiratory infections","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001873","label":"Thrombocytopenia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001627","label":"Abnormal heart morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001344","label":"Absent speech","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0006536","label":"Airway obstruction","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001631","label":"Atrial septal defect","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001635","label":"Congestive heart failure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002159","label":"Heparan sulfate excretion in urine","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001639","label":"Hypertrophic cardiomyopathy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003073","label":"Hypoalbuminemia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001265","label":"Hyporeflexia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002540","label":"Inability to walk","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001387","label":"Joint stiffness","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001882","label":"Leukopenia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000158","label":"Macroglossia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000100","label":"Nephrotic syndrome","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000648","label":"Optic atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001643","label":"Patent ductus arteriosus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002092","label":"Pulmonary arterial hypertension","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0031123","label":"Recurrent gastroenteritis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002098","label":"Respiratory distress","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001649","label":"Tachycardia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001072","label":"Thickened skin","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003541","label":"Urinary glycosaminoglycan excretion","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001928","label":"Abnormality of coagulation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007703","label":"Abnormality of retinal pigmentation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001552","label":"Barrel-shaped chest","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0005528","label":"Bone marrow hypocellularity","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012444","label":"Brain atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0410263","label":"Brain imaging abnormality","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002514","label":"Cerebral calcification","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000509","label":"Conjunctivitis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004315","label":"Decreased circulating IgG level","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006191","label":"Deep palmar crease","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012448","label":"Delayed myelination","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000105","label":"Enlarged kidney","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000286","label":"Epicanthus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000293","label":"Full cheeks","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012597","label":"Heavy proteinuria","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100790","label":"Hernia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000238","label":"Hydrocephalus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000998","label":"Hypertrichosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001252","label":"Hypotonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003496","label":"Increased circulating IgM level","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000527","label":"Long eyelashes","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002938","label":"Lumbar hyperlordosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008454","label":"Lumbar kyphosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001653","label":"Mitral regurgitation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000639","label":"Nystagmus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001655","label":"Patent foramen ovale","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000768","label":"Pectus carinatum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000629","label":"Periorbital fullness","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011220","label":"Prominent forehead","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100806","label":"Sepsis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000470","label":"Short neck","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003196","label":"Short nose","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002652","label":"Skeletal dysplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010307","label":"Stridor","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000506","label":"Telecanthus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100874","label":"Thick hair","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012471","label":"Thick vermilion border","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002942","label":"Thoracic kyphosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0005180","label":"Tricuspid regurgitation","frequency":"Occasional (29-5%)","criteria":null}]}}