Natural History in Fabry Patients With IVS4+919G>A Mutation

NCT03222336 | Unknown

• 1 other identifier: Fabry Version 1.0 VGHTP 2016
• Study Type: observational
• Target: 80
• Locations: 0 countries
• Sites: N/A

Brief Summary

Fabry disease is caused by the deficiency or absence of alpha-galactosidase A (α-Gal A) activity, leading to progressive deposition of glycosphingolipids, mainly globotriaosylceramide (Gb3), in the lysosomes of multiple tissues and organs. In Taiwan, Dr. Niu first revealed a surprisingly high incidence (approximately one in 1,600 males) of a cardiac variant GLA splicing mutation, IVS4+919G\>A, in newborn screening. Patients who carried the IVS4 + 919G \> A mutation and were older than 40 years had a higher prevalence of hypertrophic cardiomyopathy. Endocardial biopsy of these patients with hypertrophic cardiomyopathy showed significant Gb3 accumulation in the cardiomyocytes. Although the hotspot IVS4+919G\>A mutation is now being observed with greater frequency, understanding of the natural course of cardiac variant Fabry disease with this specific mutation remains limited. Therefore, our study would like to conduct a study to approach the natural history among patients with Chinese hotspot late-onset Fabry mutation IVS4+919G\>A through family pedigree analysis.

Conditions

Fabry Disease, Cardiac Variant

Outcome Measures

Primary Outcomes (1)

• Completeness of IVS4 family tree mapping and obligate carrier identification within their family pedigree

  First patient in : 30-Sep-2017; Last Patient out : 1-June-2020

Interventions

Family pedigree and data collection BEHAVIORAL

1. Enroll first generation (newborn), at least one member from second (parent) and third generation (grandparent) for a complete IVS4 family tree mapping. 2. Collect and analyze medical history, genetic and biochemical assessment data

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This prospective family screening study aim to enrol family members from pre-identified IVS4 female newborn's family. IVS4 female newborn's family member will be invited to join the family screening study with written informed consent prior to any specific study procedure. After written informed consent process, a series of screening examination will be conducted at screening visit which included medical history interview, physical examination, α-Gal A enzyme activity test, genetic test, plasma lyso-GB3, renal function and cardiac function assessment as well as pedigree data analysis for IVS4 family tree mapping.

You may qualify if:

• Fabry IVS4 female newborn family members.
• Patients and/or their legal representatives who are willing to provide written informed consent

You may not qualify if:

• No blood relatives to the IVS4 female newborn family

Sponsors & Collaborators

• Taipei Veterans General Hospital, Taiwan: lead
• Sanofi: collaborator

Related Publications (12)

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  PMID: 20360539 BACKGROUND

• Chong KW, Lu YH, Hsu JH, Lo MY, Hsiao CY, Niu DM (2008) High incidence of cardiac variant of Fabry disease in Taiwanese revealed by newborn screening Conference High incidence of cardiac variant of Fabry disease in Taiwanese revealed by newborn screening, Hualien, Taiwan, 2008, pp 92-98

  BACKGROUND

• Deegan PB, Baehner AF, Barba Romero MA, Hughes DA, Kampmann C, Beck M; European FOS Investigators. Natural history of Fabry disease in females in the Fabry Outcome Survey. J Med Genet. 2006 Apr;43(4):347-52. doi: 10.1136/jmg.2005.036327. Epub 2005 Oct 14.

  PMID: 16227523 BACKGROUND

• Desnick RJ, Ioannou YA, Eng CM (2001) a-Galactosidase A deficiency: Fabry disease. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic and molecular bases of inherited disease. McGraw-Hill, New York, pp 3733-3774

  BACKGROUND

• Lin HY, Huang CH, Yu HC, Chong KW, Hsu JH, Lee PC, Cheng KH, Chiang CC, Ho HJ, Lin SP, Chen SJ, Lin PK, Niu DM. Enzyme assay and clinical assessment in subjects with a Chinese hotspot late-onset Fabry mutation (IVS4 + 919G-->A). J Inherit Metab Dis. 2010 Oct;33(5):619-24. doi: 10.1007/s10545-010-9166-7. Epub 2010 Sep 7.

  PMID: 20821055 BACKGROUND

• Mehta A, Ricci R, Widmer U, Dehout F, Garcia de Lorenzo A, Kampmann C, Linhart A, Sunder-Plassmann G, Ries M, Beck M. Fabry disease defined: baseline clinical manifestations of 366 patients in the Fabry Outcome Survey. Eur J Clin Invest. 2004 Mar;34(3):236-42. doi: 10.1111/j.1365-2362.2004.01309.x.

  PMID: 15025684 BACKGROUND

• Nakao S, Takenaka T, Maeda M, Kodama C, Tanaka A, Tahara M, Yoshida A, Kuriyama M, Hayashibe H, Sakuraba H, et al. An atypical variant of Fabry's disease in men with left ventricular hypertrophy. N Engl J Med. 1995 Aug 3;333(5):288-93. doi: 10.1056/NEJM199508033330504.

  PMID: 7596372 BACKGROUND

• Nakao S, Kodama C, Takenaka T, Tanaka A, Yasumoto Y, Yoshida A, Kanzaki T, Enriquez AL, Eng CM, Tanaka H, Tei C, Desnick RJ. Fabry disease: detection of undiagnosed hemodialysis patients and identification of a "renal variant" phenotype. Kidney Int. 2003 Sep;64(3):801-7. doi: 10.1046/j.1523-1755.2003.00160.x.

  PMID: 12911529 BACKGROUND

• Ries M, Gupta S, Moore DF, Sachdev V, Quirk JM, Murray GJ, Rosing DR, Robinson C, Schaefer E, Gal A, Dambrosia JM, Garman SC, Brady RO, Schiffmann R. Pediatric Fabry disease. Pediatrics. 2005 Mar;115(3):e344-55. doi: 10.1542/peds.2004-1678. Epub 2005 Feb 15.

  PMID: 15713906 BACKGROUND

• von Scheidt W, Eng CM, Fitzmaurice TF, Erdmann E, Hubner G, Olsen EG, Christomanou H, Kandolf R, Bishop DF, Desnick RJ. An atypical variant of Fabry's disease with manifestations confined to the myocardium. N Engl J Med. 1991 Feb 7;324(6):395-9. doi: 10.1056/NEJM199102073240607. No abstract available.

  PMID: 1846223 BACKGROUND

• Tai CL, Liu MY, Yu HC, Chiang CC, Chiang H, Suen JH, Kao SM, Huang YH, Wu TJ, Yang CF, Tsai FC, Lin CY, Chang JG, Chen HD, Niu DM. The use of high resolution melting analysis to detect Fabry mutations in heterozygous females via dry bloodspots. Clin Chim Acta. 2012 Feb 18;413(3-4):422-7. doi: 10.1016/j.cca.2011.10.023. Epub 2011 Oct 29.

  PMID: 22063097 BACKGROUND

• Wilcox WR, Oliveira JP, Hopkin RJ, Ortiz A, Banikazemi M, Feldt-Rasmussen U, Sims K, Waldek S, Pastores GM, Lee P, Eng CM, Marodi L, Stanford KE, Breunig F, Wanner C, Warnock DG, Lemay RM, Germain DP; Fabry Registry. Females with Fabry disease frequently have major organ involvement: lessons from the Fabry Registry. Mol Genet Metab. 2008 Feb;93(2):112-28. doi: 10.1016/j.ymgme.2007.09.013. Epub 2007 Nov 26.

  PMID: 18037317 BACKGROUND

MeSH Terms

Conditions

Fabry Disease, Cardiac Variant

Interventions

Data Collection

Intervention Hierarchy (Ancestors)

Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Central Study Contacts

Dau-Ming Niu

CONTACT

886-2-28712121; dmniu1111@yahoo.com.tw

Chih-Ya Cheng

CONTACT

886-2-28712121; chihya.cheng@gmail.com

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Pediatric Genetic and Endocrinology Division

Study Record Dates

• First Submitted: July 16, 2017
• First Posted: July 19, 2017
• Study Start: September 1, 2017
• Primary Completion: June 1, 2020
• Study Completion: September 30, 2020
• Last Updated: July 19, 2017

Record last verified: 2017-07