Genetic and Metabolic Disease in Children

NCT02650622 | Recruiting

• 1 other identifier: STU 112014-001
• Study Type: observational
• Target: 1,550
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, non-randomized, non-blinded observational study. The overarching goal is to discover new disease-associated genes in children, while establishing a specific focus on disorders where molecular characterization is most likely to lead to novel therapies. This study will merge detailed phenotypic characterization of patients presenting to the Pediatric Genetics and Metabolism Division in the Department of Pediatrics/Children's Medical Center at Dallas and collaborating clinics with Next-Generation sequencing techniques to identify disease-producing mutations. The primary objective of the study is to identify novel pathogenic mutations in children with rare Mendelian disorders. A secondary objective of the study is to establish normative ranges of a large number of metabolites from healthy newborns and older children.

Conditions

Genetic Diseases; Metabolic Diseases

Keywords

Metabolism; Genetics; Metabolomics; Genomics

Outcome Measures

Primary Outcomes (1)

• Perform metabolomic profiling and exome sequencing in children with presumed genetic and metabolic diseases

  The Levels of the metabolites that can be detected in the plasma from the enrolled children will be measured by mass-spectrometry technique.The DNA samples will be extracted from the blood samples of diseased children and then subjected to exome sequencing to identify gene mutations.

  3-4 years

Secondary Outcomes (1)

• Perform metabolomic profiling in healthy children

  3-4 years

Other Outcomes (1)

• Establish a specimen repository of healthy and diseased children

  3 years

Study Arms (3)

Cohort 1-Newborns aged 1-2 days

No intervention will be applied specifically for this cohort. Blood samples will be collected from this cohort by piggybacking the state-mandated newborn screening test.

Cohort 2-Children aged 0-18 years

No intervention will be applied specifically for this cohort. Blood samples will be collected from this cohort by piggybacking the blood draw of patient's standard of care.

Cohort 3-Diseased childrens and families

Blood samples will be collected from this cohort by piggybacking the blood draw of patient's standard of care. Skin biopsy will be performed on the proband children with the agreement from parents or guardians.

Procedure: Skin Biopsy

Interventions

Skin Biopsy PROCEDURE

Skin biopsy will only be performed on the proband children in the cohort 3. A small piece of skin (less than 1/8'') will be removed using a local anesthetic cream and a punch, which will then be used for culture of skin cells and other laboratory tests on metabolic function.

Cohort 3-Diseased childrens and families

Eligibility Criteria

• Age: 1 Day+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Two populations will be enrolled in this study, control and diseased. Healthy newborns and older children will be recruited into the control population from Parkland Postpartum units and Children's Medical Center (CMC), respectively. The diseased population will be recruited from the clinics of the Pediatric Genetics and Metabolism Division in the Department of Pediatrics of CMC.

You may qualify if:

• Subjects aged 1-2 days
• Subjects with gestational age 37-42 weeks
• Subjects with stable clinical status (admitted to normal newborn nursery)
• Subjects aged 0-18 years
• Subjects (no age limit) with ANY phenotype as below:
• Confirmed metabolic or genetic diseases
• Suspected metabolic or genetic diseases
• Episodic metabolic decompensation (e.g. hypoglycemia, hyperammonemia, metabolic acidosis)
• Developmental regression
• Major congenital malformation
• Other unexplained symptoms of potential genetic origin

You may not qualify if:

• Subjects with gestational age \<37 weeks or \>42 weeks
• Subjects with overt signs of metabolic dysfunction, distress or genetic diseases including hypoglycemia, hyperglycemia, sepsis/shock, hypoxemia, or major congenital malformation
• Subjects with mothers whose pregnancies were complicated by gestational diabetes, gestational hyperglycemia, gestational hypertension, preeclampsia, or any other major disorders.
• Subjects with confirmed metabolic or genetic diseases
• Subjects with suspected metabolic or genetic diseases
• Subjects with episodic metabolic decompensation (e.g. hypoglycemia, hyperammonemia, metabolic acidosis)
• Subjects with developmental regression
• Subjects with major congenital malformation

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

Study Sites (1)

Children's Medical Center at Dallas

Dallas, Texas, 75390, United States

RECRUITING

Related Publications (2)

• Scriver CR, Neal JL, Saginur R, Clow A. The frequency of genetic disease and congenital malformation among patients in a pediatric hospital. Can Med Assoc J. 1973 May 5;108(9):1111-5.

  PMID: 4704890 BACKGROUND

• Ng SB, Buckingham KJ, Lee C, Bigham AW, Tabor HK, Dent KM, Huff CD, Shannon PT, Jabs EW, Nickerson DA, Shendure J, Bamshad MJ. Exome sequencing identifies the cause of a mendelian disorder. Nat Genet. 2010 Jan;42(1):30-5. doi: 10.1038/ng.499. Epub 2009 Nov 13.

  PMID: 19915526 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

There are 3 cohorts in this study: Cohort 1: healthy newborns Cohort 2: healthy children aged 0-18 years old Cohort 3: Children with genetic/metabolic disorders and their families Blood samples will be collected from all the three cohorts for isolation of plasma for metabolomic analysis. In addition, DNA will be extracted from the blood samples of cohort 3 patients for genomic sequencing, and skin fibroblast cells will be collected from the proband patients in cohort 3.

MeSH Terms

Conditions

Genetic Diseases, Inborn; Metabolic Diseases

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases

Study Officials

• Ralph J DeBerardinis, MD, PhD

  UT Southwestern Medical Center, Children's Medical Center at Dallas

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Christine Quinn, MS,CGC

CONTACT

214-456-2067; christine.quinn@childrens.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PROFESSOR

Study Record Dates

• First Submitted: January 6, 2016
• First Posted: January 8, 2016
• Study Start: June 1, 2015
• Primary Completion (Estimated): May 1, 2030
• Study Completion (Estimated): May 1, 2030
• Last Updated: June 26, 2025

Record last verified: 2024-06

Locations

US (1)