title: [Acid sphingomyelinase deficiency (Niemann-Pick disease type B) in adulthood: A retrospective multicentric study of 28 adult cases].
abstract: BACKGROUND
  Acid sphingomyelinase deficiency (ASMD) is an autosomal recessive disease with a clinical spectrum ranging from a neurovisceral infantile form (Niemann-Pick disease type A) to a chronic visceral form also encountered in adults (Niemann-Pick disease type B, NP-B).
  
  
  METHODS
  Retrospective multicentric analysis of French adult patients with ASMD over the period 1985-March 2015. Clinical, biological, and imaging data were analyzed.
  
  
  RESULTS
  Twenty-eight patients (19 males, 9 females) were analyzed. Diagnosis was made before the age of 10 years in 16 cases. Main symptoms at diagnosis were spleen/liver enlargement and interstitial lung disease. Biological abnormalities included: thrombocytopenia (platelet count <150 000/mm3) in 24 cases including 4 patients with platelet count <60 000/mm3, constantly low high-density lipoprotein (HDL) cholesterol, polyclonal hypergammaglobulinemia (n=6), monoclonal gammopathy of unknown significance (n=5), normal prothrombin level discordant with low factor V (n=5), elevated chitotriosidase level (n=11). The diagnosis was confirmed in all cases by deficient acid sphingomyelinase enzyme activity. SMPD1 gene sequencing was performed in 25 cases. The frequent p.R610del mutation was largely predominant, constituting 62% of the non-related alleles. During the follow-up period, three patients died before 50 years of age from cirrhosis, heart failure and lung insufficiency, respectively.
  
  
  CONCLUSIONS
  ASMD in adulthood (NP-B) associates spleen/liver enlargement and interstitial lung disease. Early diagnosis and appropriate management are essential for reducing the risk of complications, improving quality of life, and avoiding inappropriate procedures such as splenectomy. To date, only symptomatic therapy is available. A phase 2/3 therapeutic trial with IV infusion of recombinant enzyme is on-going.
authors.affiliation: Service de médecine interne-rhumatologie, groupe hospitalier Diaconesses-Croix-Saint-Simon, 125, rue d'Avron, 75020 Paris, France; Centre de référence des maladies lysosomales, site Avron, 75020 Paris, France; UMRS 974, équipe muscle inflammatoire/thérapies innovantes ciblées, Inserm, université Pierre-et-Marie-Curie, groupe hospitalier Pitié-Salpêtrière, 47-83, boulevard de l'Hôpital, 75013 Paris, France. Electronic address: olidove@hopital-dcss.org.
authors.forename: O
authors.initials: O
authors.lastname: Lidove
authors.affiliation: Centre de référence des maladies lysosomales, site Avron, 75020 Paris, France; Service de médecine interne, hôpitaux universitaires Paris Nord-Val-de-Seine, Beaujon, Assistance publique-Hôpitaux de Paris, 100, boulevard du Général-Leclerc, 92110 Clichy, France.
authors.forename: N
authors.initials: N
authors.lastname: Belmatoug
authors.affiliation: Maladies héréditaires du métabolisme et dépistage néonatal, CHU de Lyon, 69000 Lyon, France.
authors.forename: R
authors.initials: R
authors.lastname: Froissart
authors.affiliation: Médecine interne et maladies vasculaires, CHU d'Angers, 4, rue Larrey, 49933 Angers cedex, France.
authors.forename: C
authors.initials: C
authors.lastname: Lavigne
authors.affiliation: Médecine interne, groupe hospitalier Sud, université de Lyon, hospices civils de Lyon, 69495 Pierre-Bénite, France.
authors.forename: I
authors.initials: I
authors.lastname: Durieu
authors.affiliation: Médecine interne-immunologie clinique, centre de référence des maladies héréditaires du métabolisme, CHU Conception, AP-HM, 13000 Marseille, France.
authors.forename: K
authors.initials: K
authors.lastname: Mazodier
authors.affiliation: Département de médecine interne, hôpital Trois-Chêne, hôpitaux universitaires de Genève, 3, chemin de Pont-Bochet, 1226 Thonex, Genève, Suisse.
authors.forename: C
authors.initials: C
authors.lastname: Serratrice
authors.affiliation: Endocrinologie et maladies héréditaires du métabolisme, hôpital Huriez, CHRU Lille, rue Polonovski, 59037 Lille, France.
authors.forename: C
authors.initials: C
authors.lastname: Douillard
authors.affiliation: Laboratoire de génétique moléculaire, CHU de Bordeaux, 33000 Bordeaux, France.
authors.forename: C
authors.initials: C
authors.lastname: Goizet
authors.affiliation: Médecine interne, hôpital Nord, CHU de Saint-Étienne, 42055 Saint-Étienne cedex 2, France.
authors.forename: P
authors.initials: P
authors.lastname: Cathebras
authors.affiliation: Service de neurologie, hôpital de la Tronche, 38000 Grenoble, France.
authors.forename: G
authors.initials: G
authors.lastname: Besson
authors.affiliation: Médecine 2, hôpital Pitié-Salpêtrière, 47-83, boulevard de l'Hôpital, 75013 Paris, France.
authors.forename: Z
authors.initials: Z
authors.lastname: Amoura
authors.affiliation: Service de pneumologie, centre de référence de l'histiocytose langerhansienne, hôpital St-Louis, 75010 Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Tazi
authors.affiliation: Service de médecine interne, hôpital Saint-Antoine, 75012 Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Gatfossé
authors.affiliation: Service de médecine interne, hôpital Saint-Antoine, 75012 Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Rivière
authors.affiliation: Service de médecine interne-rhumatologie, groupe hospitalier Diaconesses-Croix-Saint-Simon, 125, rue d'Avron, 75020 Paris, France.
authors.forename: T
authors.initials: T
authors.lastname: Sené
authors.affiliation: Inserm U 820, faculté de médecine, RTH Laennec, 69000 Lyon, France.
authors.forename: M T
authors.initials: MT
authors.lastname: Vanier
authors.affiliation: Service de médecine interne-rhumatologie, groupe hospitalier Diaconesses-Croix-Saint-Simon, 125, rue d'Avron, 75020 Paris, France.
authors.forename: J-M
authors.initials: JM
authors.lastname: Ziza
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D005260:Female; D005602:France / Q000453:epidemiology; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D052537:Niemann-Pick Disease, Type B / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D010641:Phenotype; D012189:Retrospective Studies; D013108:Sphingomyelin Phosphodiesterase / Q000172:deficiency / Q000235:genetics; D055815:Young Adult
chemical_list: D013108:Sphingomyelin Phosphodiesterase
keywords: Acid sphingomyelinase deficiency; Adult; Adulte; Fibrose pulmonaire; Gammapathie monoclonale; Lung fibrosis; Maladie de Niemann-Pick B; Monoclonal gammopathy; Niemann-Pick disease type B; Sphingomyélinase acide; Splenomegaly; Splénomégalie