Screening for Gaucher Disease and Acid Sphingomyelinase Deficiency

Screening for Gaucher Disease and Acid Sphingomyelinase Deficiency From Taiwanese Candidates With Splenomegaly and/or Thrombocytopenia

High-risk screening for Gaucher disease and Acid Sphingomyelinase Deficiency in patients with splenomegaly and/or thrombocytopenia in Taiwan

Study Overview

• Status: Not yet recruiting
• Conditions: Gaucher Disease

Detailed Description

Late-onset Gaucher disease (GD) present a unique set of challenges compared to their early-onset counterparts. Symptoms may not appear until adulthood, leading to delayed diagnosis and treatment. This delay can result in irreversible damage to affected tissues and organs, such as the liver, spleen, and central nervous system. Additionally, many late-onset GD are underdiagnosed or misdiagnosed due to their rarity and the variability of symptoms. This study is divided into two phases. In the first phase, patients with hepatosplenomegaly of unknown etiology will be initially screened using an electronic medical record database, and in the second phase, laboratory analysis of biomarkers, including Dry blood spot (DBS) for GBA1 enzyme activity, plasma Lyso-GB1 levels and GBA1 gene sequencing, will be performed. Acid sphingomyelinase deficiency (ASMD) is another lysosomal storage disorder that shares symptoms with GD. Consistent with the above screening strategy for GD patients in two phases (DBS for ASM enzyme activity, plasma Lyso-SM levels and ASM gene sequencing). This study will involve 2,000 candidates from electronic healthcare databases, 240 patients from outpatient clinics, and a cohort of 6 GD1/GD3 patients as controls. In conclusion, initial screening for late-onset GD and ASMD can provide patients with treatment opportunities that can improve outcomes for those affected by these rare diseases.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Chung-Hsing Wang; Phone Number: 14641 0422032798; Email: 005894@tool.caaumed.org.tw
• Study Contact Backup: Name: Kai-Wen liu; Phone Number: 14131 0422032798; Email: kevinagirl2@gmail.com

Study Locations

• Taiwan
  • Taichung, Taiwan
    • China Medical University Hospita
    • Contact: Chung-Hsing Wang; Phone Number: 14641 0422032798

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patient of gaucher disease or acid sphingomyelinase

Description

Inclusion Criteria:

1. Clinical diagnosis of splenomegaly
2. Clinical diagnosis of thrombocytopenia

Exclusion Criteria:

1. Clinical diagnosis of gaucher disease
2. Clinical diagnosis of acid sphingomyelinase
3. Clinical diagnosis of malignant tumors

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
candidates; In the first phase, patients with hepatosplenomegaly of unknown etiology will be initially screened using an electronic medical record database, and in the second phase, laboratory analysis of biomarkers, including Dry blood spot (DBS) for GBA1 enzyme activity, plasma Lyso-GB1 levels and GBA1 gene sequencing, will be performed.
control; Compare the blood test with the candidates group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Confirmation of Disease	DBS for GBA1 enzyme activity or ASM enzyme activity positive、GBA1 gene sequencing or ASM gene sequencing positive	1 month

Collaborators and Investigators

• Sponsor: Chung-Hsing Wang
• Collaborators: Sanofi
• Investigators: Principal Investigator: Chung-Hsing Wang, China Medical University Hospital

Publications and helpful links

General Publications

• Wan L, Hsu CM, Tsai CH, Lee CC, Hwu WL, Tsai FJ. Mutation analysis of Gaucher disease patients in Taiwan: high prevalence of the RecNciI and L444P mutations. Blood Cells Mol Dis. 2006 May-Jun;36(3):422-5. doi: 10.1016/j.bcmd.2006.02.001. Epub 2006 Mar 20.
• Revel-Vilk S, Fuller M, Zimran A. Value of Glucosylsphingosine (Lyso-Gb1) as a Biomarker in Gaucher Disease: A Systematic Literature Review. Int J Mol Sci. 2020 Sep 28;21(19):7159. doi: 10.3390/ijms21197159.
• Pinto C, Sousa D, Ghilas V, Dardis A, Scarpa M, Macedo MF. Acid Sphingomyelinase Deficiency: A Clinical and Immunological Perspective. Int J Mol Sci. 2021 Nov 28;22(23):12870. doi: 10.3390/ijms222312870.
• McGovern MM, Avetisyan R, Sanson BJ, Lidove O. Disease manifestations and burden of illness in patients with acid sphingomyelinase deficiency (ASMD). Orphanet J Rare Dis. 2017 Feb 23;12(1):41. doi: 10.1186/s13023-017-0572-x.
• Jones SA, McGovern M, Lidove O, Giugliani R, Mistry PK, Dionisi-Vici C, Munoz-Rojas MV, Nalysnyk L, Schecter AD, Wasserstein M. Clinical relevance of endpoints in clinical trials for acid sphingomyelinase deficiency enzyme replacement therapy. Mol Genet Metab. 2020 Sep-Oct;131(1-2):116-123. doi: 10.1016/j.ymgme.2020.06.008. Epub 2020 Jun 24.
• Loftus WK, Metreweli C. Normal splenic size in a Chinese population. J Ultrasound Med. 1997 May;16(5):345-7.

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: February 6, 2024
• First Submitted That Met QC Criteria: February 6, 2024
• First Posted (Actual): February 14, 2024

Study Record Updates

• Last Update Posted (Estimated): April 15, 2024
• Last Update Submitted That Met QC Criteria: April 12, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Lymphatic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Lipidoses; Lipid Metabolism, Inborn Errors; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Niemann-Pick Diseases; Niemann-Pick Disease, Type A; Niemann-Pick Disease, Type C; Gaucher Disease
• Other Study ID Numbers: CMUH112-REC2-098

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No