Study of Genetic and Metabolic Disorders in Children to Identify New Disease Genes and Metabolic Profiles

What this Trial Is About

Researchers are conducting a prospective, non-randomized observational study to discover new disease-associated genes in children, focusing especially on rare Mendelian and metabolic disorders. The study aims to identify novel pathogenic mutations and establish normative metabolite ranges in healthy newborns and older children. Understanding the genetic basis of these conditions may lead to new therapies, particularly for inborn errors of metabolism IEMs, which already have some effective treatments. This research integrates detailed patient evaluations with advanced genomic and metabolomic techniques to improve diagnosis and treatment options for pediatric genetic diseases. The study involves recruiting two main populations healthy controls and diseased children. For healthy newborns, blood samples are collected during routine state-mandated newborn screening, while samples from older healthy children are collected alongside clinically indicated blood draws. Diseased children undergo blood and DNA sample collection for metabolomic and genomic analysis, and skin biopsies may be performed for biological validation of novel mutations. Family members of affected children may also provide samples to assist gene identification. No specific interventions are applied outside of standard care procedures. Participants will provide samples during routine clinical visits, with evaluations including metabolomic profiling and next-generation sequencing. Healthy participants help establish normal metabolite ranges, while diseased participants samples assist in identifying metabolic abnormalities and gene mutations. Skin fibroblasts from some patients will be cultured to study mutation effects. The study monitors these measures over several years, with primary outcomes focused on metabolomic and exome sequencing in affected children and secondary outcomes on metabolomic profiling in healthy children. The total study duration extends until May 2030.

Genetic and Metabolic Disease in Children