Practice Guideline

. 2023 Apr 17;18(1):85.

doi: 10.1186/s13023-023-02686-6.

Consensus clinical management guidelines for acid sphingomyelinase deficiency (Niemann-Pick disease types A, B and A/B)

Tarekegn Geberhiwot^{1

2}, Melissa Wasserstein³, Subadra Wanninayake⁴, Shaun Christopher Bolton⁴, Andrea Dardis⁵, Anna Lehman⁶, Olivier Lidove⁷, Charlotte Dawson⁴, Roberto Giugliani⁸, Jackie Imrie⁹, Justin Hopkin¹⁰, James Green⁹, Daniel de Vicente Corbeira¹¹, Shyam Madathil¹², Eugen Mengel¹³, Fatih Ezgü¹⁴, Magali Pettazzoni¹⁵, Barbara Sjouke¹⁶, Carla Hollak¹⁶, Marie T Vanier¹⁷, Margaret McGovern¹⁸, Edward Schuchman¹⁹

Affiliations

¹ University Hospital Birmingham NHS Foundation Trust, Birmingham, UK. Tarekegn.hiwot@uhb.nhs.uk.
² Institute of Metabolism and System Research, University of Birmingham, Birmingham, UK. Tarekegn.hiwot@uhb.nhs.uk.
³ Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, USA.
⁴ University Hospital Birmingham NHS Foundation Trust, Birmingham, UK.
⁵ Regional Coordinator Centre for Rare Disease, AMC Hospital of Udine, Udine, Italy.
⁶ Department of Medical Genetics, University of British Columbia, Vancouver, BC, V6T 1Z2, Canada.
⁷ Department of Internal Medicine, Hôpital de La Croix Saint Simon, Paris, France.
⁸ BioDiscovery and DR BRASIL Research Group, HCPA, Department of Genetics and PPGBM, UFRGS, INAGEMP, DASA, and Casa Dos Raros, Porto Alegre, Brazil.
⁹ International Niemann-Pick Disease Registry, Newcastle, UK.
¹⁰ National Niemann-Pick Disease Foundation, Fort Atkinson, WI, USA.
¹¹ ASMD España, Madrid, Spain.
¹² Department of Respiratory Medicine, University Hospital Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Birmingham, UK.
¹³ Institute of Clinical Science in LSD, SphinCS, Hochheim, Germany.
¹⁴ Division of Pediatric Metabolism and Division of Pediatric Genetics, Department of Pediatrics, Gazi University Faculty of Medicine, 06560, Ankara, Turkey.
¹⁵ Biochemistry and Molecular Biology and Reference Center for Inherited Metabolic Disorders, Hospices Civils de Lyon, 59 Boulevard Pinel, 69677, Bron Cedex, France.
¹⁶ Department of Endocrinology and Metabolism, Amsterdam University Medical Centers, Academic Medical Center, University of Amsterdam, F5-169, P.O. Box 22660, 1100 DD, Amsterdam, The Netherlands.
¹⁷ INSERM, Hospices Civils de Lyon, Lyon, France.
¹⁸ Yale School of Medicine, New Haven, CT, USA.
¹⁹ Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, Room 14-20A, New York, NY, 10029, USA.

PMID: 37069638
PMCID: PMC10108815
DOI: 10.1186/s13023-023-02686-6

Practice Guideline

Consensus clinical management guidelines for acid sphingomyelinase deficiency (Niemann-Pick disease types A, B and A/B)

Tarekegn Geberhiwot et al. Orphanet J Rare Dis. 2023.

. 2023 Apr 17;18(1):85.

doi: 10.1186/s13023-023-02686-6.

Authors

Affiliations

¹ University Hospital Birmingham NHS Foundation Trust, Birmingham, UK. Tarekegn.hiwot@uhb.nhs.uk.
² Institute of Metabolism and System Research, University of Birmingham, Birmingham, UK. Tarekegn.hiwot@uhb.nhs.uk.
³ Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, USA.
⁴ University Hospital Birmingham NHS Foundation Trust, Birmingham, UK.
⁵ Regional Coordinator Centre for Rare Disease, AMC Hospital of Udine, Udine, Italy.
⁶ Department of Medical Genetics, University of British Columbia, Vancouver, BC, V6T 1Z2, Canada.
⁷ Department of Internal Medicine, Hôpital de La Croix Saint Simon, Paris, France.
⁸ BioDiscovery and DR BRASIL Research Group, HCPA, Department of Genetics and PPGBM, UFRGS, INAGEMP, DASA, and Casa Dos Raros, Porto Alegre, Brazil.
⁹ International Niemann-Pick Disease Registry, Newcastle, UK.
¹⁰ National Niemann-Pick Disease Foundation, Fort Atkinson, WI, USA.
¹¹ ASMD España, Madrid, Spain.
¹² Department of Respiratory Medicine, University Hospital Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Birmingham, UK.
¹³ Institute of Clinical Science in LSD, SphinCS, Hochheim, Germany.
¹⁴ Division of Pediatric Metabolism and Division of Pediatric Genetics, Department of Pediatrics, Gazi University Faculty of Medicine, 06560, Ankara, Turkey.
¹⁵ Biochemistry and Molecular Biology and Reference Center for Inherited Metabolic Disorders, Hospices Civils de Lyon, 59 Boulevard Pinel, 69677, Bron Cedex, France.
¹⁶ Department of Endocrinology and Metabolism, Amsterdam University Medical Centers, Academic Medical Center, University of Amsterdam, F5-169, P.O. Box 22660, 1100 DD, Amsterdam, The Netherlands.
¹⁷ INSERM, Hospices Civils de Lyon, Lyon, France.
¹⁸ Yale School of Medicine, New Haven, CT, USA.
¹⁹ Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, Room 14-20A, New York, NY, 10029, USA.

PMID: 37069638
PMCID: PMC10108815
DOI: 10.1186/s13023-023-02686-6

Abstract

Background: Acid Sphingomyelinase Deficiency (ASMD) is a rare autosomal recessive disorder caused by mutations in the SMPD1 gene. This rarity contributes to misdiagnosis, delayed diagnosis and barriers to good care. There are no published national or international consensus guidelines for the diagnosis and management of patients with ASMD. For these reasons, we have developed clinical guidelines that defines standard of care for ASMD patients.

Methods: The information contained in these guidelines was obtained through a systematic literature review and the experiences of the authors in their care of patients with ASMD. We adopted the Appraisal of Guidelines for Research and Evaluation (AGREE II) system as method of choice for the guideline development process.

Results: The clinical spectrum of ASMD, although a continuum, varies substantially with subtypes ranging from a fatal infantile neurovisceral disorder to an adult-onset chronic visceral disease. We produced 39 conclusive statements and scored them according to level of evidence, strengths of recommendations and expert opinions. In addition, these guidelines have identified knowledge gaps that must be filled by future research.

Conclusion: These guidelines can inform care providers, care funders, patients and their carers about best clinical practice and leads to a step change in the quality of care for patients with ASMD with or without enzyme replacement therapy (ERT).

Keywords: ASMD; Acid sphingomyelinase deficiency; Diagnosis; Guidelines; Management; Niemann–Pick disease; Niemann–Pick disease-a,b,a/b.

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Conflict of interest statement

Sanofi has provided financial support to AD, AL, ES, OL, RG, SCB and TH, research grant to ES and TH, and honorarium to AD, ES, OL, MTV and RG. Honorarium has been provided by Orphazyme to AD and MTV.

Figures

**Fig. 1**
Algorithm for the laboratory diagnosis of ASMD. (a) Significant increase of 3β,5α,6β-cholestane-triol (C-triol), 7-ketocholesterol (7-KC), 3β,5α,6β-trihydroxy-cholanoyl-glycine (TCG), lysosphingomyelin (lyso-SM), N-palmitoyl-O-phosphocholine-serine (PPCS). A difference with an NPC profile is the normal or slightly elevated lyso-SM level in the latter. Other causes of elevated C-triol levels include cerebro tendinous xanthomatosis (CTX) and acid lipase deficiency. (b) LC–MS/MS (or radioisotopic) preferred methods (see Statement 13). (c) Recommendation for ASM in DBS to be confirmed on leukocytes or by genetic testing. (d) Importance of parental study. **(e)** MLPA/RNA analysis. VUS: Variant of uncertain significance

See this image and copyright information in PMC

References

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Consensus clinical management guidelines for acid sphingomyelinase deficiency (Niemann-Pick disease types A, B and A/B)

Affiliations

Consensus clinical management guidelines for acid sphingomyelinase deficiency (Niemann-Pick disease types A, B and A/B)

Authors

Affiliations

Abstract

Conflict of interest statement

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References

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LinkOut - more resources

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Medical