Inherited Metabolic Disorders Inborn errors of metabolism
Conditions
Interventions
None listed
Sponsors
University of Galway
Eligibility
Age
No minimum to 99 Years
Inclusion criteria
Inclusion criteria: Participants with disease a) Individuals with either: - A molecular diagnosis of IMD (positive control cohort). - Suspected of having an IMD (despite exome analysis) based on HPO terms and/or a genomic variant of uncertain significance in a metabolic disease-associated gene (test cohort). - A genetic diagnosis that is not an IMD and without secondary metabolic dysfunction (negative control cohort). - Gaucher disease (cohort for personalised patient management) b) Patients or legal representatives give written informed consent to study participation and consent for the collection and analysis of both blood and urine samples, and where indicated, a fibroblast sample. c) Patients enrolled with a patient registry or cohort study (with ethical approval at site), such as; U-IMD, GENOMIT or Solve-RD. Healthy Participants a) Participants (children and adults) who do not have a disease or history of clinically significant systemic disease. i) No medical history of IMD, suspected IMD, or any other condition that could lead to clinically significant secondary metabolic abnormalities; ii) No medical history of malignant tumors; iii) No medical history of clinically significant systemic diseases (cardiovascular, diabetes, hypertension, respiratory, gastrointestinal, nervous, urinary, endocrine, musculoskeletal, mental disorders, and addiction); iv) No medical history of chronic systemic infectious diseases, such as HIV, Infectious hepatitis, tuberculosis, or Creutzfeldt-Jakob disease; b) Individuals or legal representatives give written informed consent to study participation and consent for the collection and analysis of both blood and urine samples.
Exclusion criteria
Exclusion criteria: Participants with diseasea) Patients or legal representatives unwilling to consent. b) Legal representatives (in the case where patients > 18 years of age are assessed unable to consent) advise against inclusion in the study. c) Patients that have had a blood transfusion within the last month and patients having haemodialysis will be excluded from metabolomic and proteomic profiling studies and from targeted metabolite and enzyme analysis studies. d) Pregnant or lactating women. e) Patients with a medical history of chronic systemic infectious diseases, such as HIV, Infectious hepatitis, tuberculosis, or Creutzfeldt-Jakob disease. Healthy Participants a) Participants that are a potential or confirmed carrier of an IMD pathogenic variant. b) Individuals or legal representatives unwilling to consent. c) Legal representatives advise against inclusion in the study. d) Pregnant or lactating women.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary outcome of this study is the systematic classification of patients with IMDs according to distinct genetic variants in metabolic pathways, along with molecular mechanistic features that correlate with clinical phenotypic severity. | — |
Secondary
| Measure | Time frame |
|---|---|
| Reduced time to diagnosis for IMD patients through personalized computational modeling integrating omics data.Identification of clinically relevant compensatory and aggravating metabolic mechanisms associated with disease severity in Gaucher Disease, enabling improved patient stratification.Assessment of the feasibility of a personalized modeling software for various IMDs. | — |
Countries
Austria, Belgium, Czech Republic, Denmark, Germany, Ireland, Italy, Netherlands, Norway, Spain, Sweden, United Kingdom
Contacts
Public ContactSomasundaram Manickavasakam
University of Galway
Outcome results
None listed