A prospective, cross-sectional survey study of the natural history of niemann-pick disease type B

Margaret M. McGovern, Melissa P. Wasserstein, Roberto Giugliani, Bruno Bembi, Marie T. Vanier, Eugen Mengel, Scott E. Brodie, David Mendelson, Gwen Skloot, Robert J. Desnick, Noriko Kuriyama, Gerald F. Cox

Research output: Contribution to journalArticle

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Abstract

OBJECTIVE. The objective of this study was to characterize the clinical features of patients with Niemann-Pick disease type B and to identify efficacy end points for future clinical trials of enzyme-replacement therapy. METHODS. Fifty-nine patients who had Niemann-Pick disease type B, were at least 6 years of age, and manifested at least 2 disease symptoms participated in this multi- center, multinational, cross-sectional survey study. Medical histories; physical examinations; assessments of cardiorespiratory function, clinical laboratory data, and liver and spleen volumes; radiographic evaluation of the lungs and bone age; and quality-of-life assessments were obtained during a 2- to 3-day period. RESULTS. Fifty-three percent of the patients were male, 92% were white, and the median age was 17.6 years. The R608del mutation accounted for 25% of all disease alleles. Most patients initially presented with splenomegaly (78%) or hepatomegaly (73%). Frequent symptoms included bleeding (49%), pulmonary infections and shortness of breath (42% each), and joint/limb pain (39%). Growth was markedly delayed during adolescence. Patients commonly had low levels of platelets and high-density lipoprotein, elevated levels of low-density lipoprotein, very-low-density lipoprotein, triglycerides, leukocyte sphingomyelin, and serum chitotriosidase, and abnormal liver function test results. Nearly all patients had documented splenomegaly and hepatomegaly and interstitial lung disease. Patients commonly showed restrictive lung disease physiology with impaired pulmonary gas exchange and decreased maximal exercise tolerance. Quality of life was only mildly decreased by standardized questionnaires. The degree of splenomegaly correlated with most aspects of disease, including hepatomegaly, growth, lipid profile, hematologic parameters, and pulmonary function. CONCLUSIONS. This study documents the multisystem involvement and clinical variability of Niemann-Pick B disease. Several efficacy end points were identified for future clinical treatment studies. Because of its correlation with disease severity, spleen volume may be a useful surrogate end point in treatment trials, whereas biomarkers such as chitotriosidase also may play a role in monitoring patient treatment responses. Pediatrics.

Original languageEnglish (US)
JournalPediatrics
Volume122
Issue number2
DOIs
StatePublished - Aug 2008
Externally publishedYes

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Type B Niemann-Pick Disease
Cross-Sectional Studies
Hepatomegaly
Splenomegaly
Lung
Spleen
Biomarkers
Niemann-Pick Diseases
Quality of Life
Pulmonary Gas Exchange
Enzyme Replacement Therapy
Exercise Tolerance
Sphingomyelins
Liver Function Tests
Interstitial Lung Diseases
Arthralgia
Physiologic Monitoring
HDL Lipoproteins
Growth
LDL Lipoproteins

Keywords

  • Acid sphingomyelinase deficiency
  • Cross-sectional study
  • Lysosomal storage disorder
  • Natural history
  • Niemann pick disease

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

A prospective, cross-sectional survey study of the natural history of niemann-pick disease type B. / McGovern, Margaret M.; Wasserstein, Melissa P.; Giugliani, Roberto; Bembi, Bruno; Vanier, Marie T.; Mengel, Eugen; Brodie, Scott E.; Mendelson, David; Skloot, Gwen; Desnick, Robert J.; Kuriyama, Noriko; Cox, Gerald F.

In: Pediatrics, Vol. 122, No. 2, 08.2008.

Research output: Contribution to journalArticle

McGovern, MM, Wasserstein, MP, Giugliani, R, Bembi, B, Vanier, MT, Mengel, E, Brodie, SE, Mendelson, D, Skloot, G, Desnick, RJ, Kuriyama, N & Cox, GF 2008, 'A prospective, cross-sectional survey study of the natural history of niemann-pick disease type B', Pediatrics, vol. 122, no. 2. https://doi.org/10.1542/peds.2007-3016
McGovern, Margaret M. ; Wasserstein, Melissa P. ; Giugliani, Roberto ; Bembi, Bruno ; Vanier, Marie T. ; Mengel, Eugen ; Brodie, Scott E. ; Mendelson, David ; Skloot, Gwen ; Desnick, Robert J. ; Kuriyama, Noriko ; Cox, Gerald F. / A prospective, cross-sectional survey study of the natural history of niemann-pick disease type B. In: Pediatrics. 2008 ; Vol. 122, No. 2.
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AU - Vanier, Marie T.

AU - Mengel, Eugen

AU - Brodie, Scott E.

AU - Mendelson, David

AU - Skloot, Gwen

AU - Desnick, Robert J.

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AU - Cox, Gerald F.

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N2 - OBJECTIVE. The objective of this study was to characterize the clinical features of patients with Niemann-Pick disease type B and to identify efficacy end points for future clinical trials of enzyme-replacement therapy. METHODS. Fifty-nine patients who had Niemann-Pick disease type B, were at least 6 years of age, and manifested at least 2 disease symptoms participated in this multi- center, multinational, cross-sectional survey study. Medical histories; physical examinations; assessments of cardiorespiratory function, clinical laboratory data, and liver and spleen volumes; radiographic evaluation of the lungs and bone age; and quality-of-life assessments were obtained during a 2- to 3-day period. RESULTS. Fifty-three percent of the patients were male, 92% were white, and the median age was 17.6 years. The R608del mutation accounted for 25% of all disease alleles. Most patients initially presented with splenomegaly (78%) or hepatomegaly (73%). Frequent symptoms included bleeding (49%), pulmonary infections and shortness of breath (42% each), and joint/limb pain (39%). Growth was markedly delayed during adolescence. Patients commonly had low levels of platelets and high-density lipoprotein, elevated levels of low-density lipoprotein, very-low-density lipoprotein, triglycerides, leukocyte sphingomyelin, and serum chitotriosidase, and abnormal liver function test results. Nearly all patients had documented splenomegaly and hepatomegaly and interstitial lung disease. Patients commonly showed restrictive lung disease physiology with impaired pulmonary gas exchange and decreased maximal exercise tolerance. Quality of life was only mildly decreased by standardized questionnaires. The degree of splenomegaly correlated with most aspects of disease, including hepatomegaly, growth, lipid profile, hematologic parameters, and pulmonary function. CONCLUSIONS. This study documents the multisystem involvement and clinical variability of Niemann-Pick B disease. Several efficacy end points were identified for future clinical treatment studies. Because of its correlation with disease severity, spleen volume may be a useful surrogate end point in treatment trials, whereas biomarkers such as chitotriosidase also may play a role in monitoring patient treatment responses. Pediatrics.

AB - OBJECTIVE. The objective of this study was to characterize the clinical features of patients with Niemann-Pick disease type B and to identify efficacy end points for future clinical trials of enzyme-replacement therapy. METHODS. Fifty-nine patients who had Niemann-Pick disease type B, were at least 6 years of age, and manifested at least 2 disease symptoms participated in this multi- center, multinational, cross-sectional survey study. Medical histories; physical examinations; assessments of cardiorespiratory function, clinical laboratory data, and liver and spleen volumes; radiographic evaluation of the lungs and bone age; and quality-of-life assessments were obtained during a 2- to 3-day period. RESULTS. Fifty-three percent of the patients were male, 92% were white, and the median age was 17.6 years. The R608del mutation accounted for 25% of all disease alleles. Most patients initially presented with splenomegaly (78%) or hepatomegaly (73%). Frequent symptoms included bleeding (49%), pulmonary infections and shortness of breath (42% each), and joint/limb pain (39%). Growth was markedly delayed during adolescence. Patients commonly had low levels of platelets and high-density lipoprotein, elevated levels of low-density lipoprotein, very-low-density lipoprotein, triglycerides, leukocyte sphingomyelin, and serum chitotriosidase, and abnormal liver function test results. Nearly all patients had documented splenomegaly and hepatomegaly and interstitial lung disease. Patients commonly showed restrictive lung disease physiology with impaired pulmonary gas exchange and decreased maximal exercise tolerance. Quality of life was only mildly decreased by standardized questionnaires. The degree of splenomegaly correlated with most aspects of disease, including hepatomegaly, growth, lipid profile, hematologic parameters, and pulmonary function. CONCLUSIONS. This study documents the multisystem involvement and clinical variability of Niemann-Pick B disease. Several efficacy end points were identified for future clinical treatment studies. Because of its correlation with disease severity, spleen volume may be a useful surrogate end point in treatment trials, whereas biomarkers such as chitotriosidase also may play a role in monitoring patient treatment responses. Pediatrics.

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KW - Natural history

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