O Lidove1, N Belmatoug2, R Froissart3, C Lavigne4, I Durieu5, K Mazodier6, C Serratrice7, C Douillard8, C Goizet9, P Cathebras10, G Besson11, Z Amoura12, A Tazi13, M Gatfossé14, S Rivière14, T Sené15, M T Vanier16, J-M Ziza15. 1. 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. 2. 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. 3. Maladies héréditaires du métabolisme et dépistage néonatal, CHU de Lyon, 69000 Lyon, France. 4. Médecine interne et maladies vasculaires, CHU d'Angers, 4, rue Larrey, 49933 Angers cedex, France. 5. Médecine interne, groupe hospitalier Sud, université de Lyon, hospices civils de Lyon, 69495 Pierre-Bénite, France. 6. Médecine interne-immunologie clinique, centre de référence des maladies héréditaires du métabolisme, CHU Conception, AP-HM, 13000 Marseille, France. 7. Département de médecine interne, hôpital Trois-Chêne, hôpitaux universitaires de Genève, 3, chemin de Pont-Bochet, 1226 Thonex, Genève, Suisse. 8. Endocrinologie et maladies héréditaires du métabolisme, hôpital Huriez, CHRU Lille, rue Polonovski, 59037 Lille, France. 9. Laboratoire de génétique moléculaire, CHU de Bordeaux, 33000 Bordeaux, France. 10. Médecine interne, hôpital Nord, CHU de Saint-Étienne, 42055 Saint-Étienne cedex 2, France. 11. Service de neurologie, hôpital de la Tronche, 38000 Grenoble, France. 12. Médecine 2, hôpital Pitié-Salpêtrière, 47-83, boulevard de l'Hôpital, 75013 Paris, France. 13. Service de pneumologie, centre de référence de l'histiocytose langerhansienne, hôpital St-Louis, 75010 Paris, France. 14. Service de médecine interne, hôpital Saint-Antoine, 75012 Paris, France. 15. Service de médecine interne-rhumatologie, groupe hospitalier Diaconesses-Croix-Saint-Simon, 125, rue d'Avron, 75020 Paris, France. 16. Inserm U 820, faculté de médecine, RTH Laennec, 69000 Lyon, France.
Abstract
INTRODUCTION: 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. CONCLUSION: 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.
INTRODUCTION: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. CONCLUSION: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.