The Intensively Follow-up Examinations for Asymptomatic MPS I Infants in Taiwan

The Intensively Follow-up Examinations for Asymptomatic MPS I Infants From Nationwide Newborn Screening Program for Mucopolysaccharidoses in Taiwan.

MPS I newborn screening has been executed in Taiwan nationwide since August 2015. Infants who failed the recheck at recall were referred to MacKay Memorial Hospital for a detailed confirmatory diagnosis. Urinary first-line biochemistry examinations including urinary GAG quantification (DMB/Cre. ratio), two-dimensional electrophoresis (2-D EP), and tandem mass spectrometry assay for predominant disaccharides derived from GAGs (i.e. CS, DS, HS, and KS) were performed. If the results were positive, a confirmative diagnosis was made according to the results of leukocyte enzymatic assay and molecular DNA analysis. Up to January 31, 2019, a total of 390,793 infants had been analyzed for MPS I, in those 11 suspicious cases were referred to MacKay Memorial Hospital for confirmation. The recall rates of MPS I was 0.0028%. Four of the 11 infants were confirmed to have MPS I. The prevalence rates of MPS I was 1.02 per 100,000 live births, respectively. Infants suspected of having MPS with a positive laboratory diagnosis but without any typical, clinical manifestations are not conformed to receive ERT under the treatment guideline of ERT for MPS in Taiwan. Distinctly, the clinical manifestations of MPS are irreversible and would be worse progressively while the symptoms have shown up. Receiving ERT at this time would effectively prevent the progression of illness, but, cannot rescue or reform the irreversible physical problems. By proceeding and undergoing an intensively long-term regular physical and laboratory examinations for asymptomatic infants with MPS I can effectively control the possibility of giving an ERT in a timely fashion.

Study Overview

• Status: Recruiting
• Conditions: MPS I
• Intervention / Treatment: Other: MPS I

Detailed Description

The study hypothesis is to proceed and to undergo an intensively long-term clinical management and laboratory examinations for asymptomatic infants with MPS I in order to be able to give an enzyme replacement therapy (ERT) in a timely fashion. The overall objectives of this study are summarized as follows, including: 1. To plan a three-month or six-month interval of recall process depending on the judgment of individual case by pediatric geneticist. 2. To recall the asymptomatic MPS I infants back to MacKay Memorial Hospital for MPS follow-up examinations, including regular physical examinations for the earliest presenting symptoms such as otitis media, abdominal or inguinal hernia, and coarse facial features, as well as the urinary biochemistry glycosaminoglycan (GAG) tests. 3. To give ERT in time whenever the typical MPS signs or symptoms showed up. 4. To achieve the aim of newborn screening for MPS, "Early detection, making early diagnosis, and providing early therapy can effectively prevent the development of severe clinical manifestations".

• Study Type: Observational
• Enrollment (Anticipated): 20

Contacts and Locations

• Study Contact: Name: Shuan-Pei Lin, MD; Phone Number: 3089 +886-2-2543-3535; Email: 4535lin@gmail.com
• Study Contact Backup: Name: Fran Sisca, MS; Phone Number: 2350 +886-2-2809-4661; Email: fran.e895@mmh.org.tw

Study Locations

• Taiwan
  • Taipei, Taiwan, 10449
    • Recruiting
    • Mackay Memorial Hospital
    • Contact: Shuan-Pei Lin, MD; Phone Number: 3089 +886-2-25433535; Email: 4535lin@gmail.com
    • Contact: Fran Sisca, MS; Phone Number: 2350 +886-2-28094661; Email: fran.e895@mmh.org.tw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 8 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The confirmed MPS I infants would be the major objects in this study for long-term inspections and assessments. In addition to this, some referral cases would be included in this study if the case is with negative GAG tests, but having been identified with two nucleotide variations or with significant reduction of IDUA enzyme activity. The estimated subject population would be 12 (11+1) in the first year, 16 (12+4) in the second year, and 20 (16+4) in the third year according to the recall rate of MPS I and the realistic situation of referred cases from newborn screening centers to MacKay Memorial Hospital.

Description

Inclusion Criteria:

• The confirmed MPS I infants

Exclusion Criteria:

• Not MPS I infants

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Find signs or symptoms of disease onset	The primary endpoint of this study is to find out any signs or symptoms of disease onset at the earliest time in order to diminish the irreversible developmental damage has taken place if the intervention of ERT is giving timely.	First Year

Collaborators and Investigators

• Sponsor: Mackay Memorial Hospital
• Collaborators: Sanofi Taiwan Co. Ltd

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2021
• Primary Completion (Anticipated): October 26, 2024
• Study Completion (Anticipated): October 26, 2024

Study Registration Dates

• First Submitted: July 1, 2021
• First Submitted That Met QC Criteria: July 1, 2021
• First Posted (Actual): July 12, 2021

Study Record Updates

• Last Update Posted (Actual): March 17, 2022
• Last Update Submitted That Met QC Criteria: March 2, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: MPS I
• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Connective Tissue Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Mucopolysaccharidoses; Mucopolysaccharidosis I
• Other Study ID Numbers: 20CT022be

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: It is yet to be decided, it will be considered after completion of primary endpoint assessment.