inborn errors of metabolism and inherited metabolic disorder
Conditions
Interventions
None listed
Sponsors
Academisch Medisch Centrum
Eligibility
Age
No minimum to 99 Years
Inclusion criteria
Inclusion criteria: Patients (any age/gender/race) with an unexplained metabolic phenotype defined as: neurological symptoms and/or abnormalities on (physical) examination suggestive of an inborn error of metabolism (energy deficiency, intoxication type or storage type) AND / OR one or more of the following suggesting a deficient metabolic pathway or process: • abnormal metabolites in body fluids (CSF, urine, blood) • functional studies at a biochemical/cellular level which indicates a metabolic deficiency (e.g. respiratory chain complex analysis) • organ dysfunction (e.g. liver or kidney failure) • abnormalities on imaging (neuro-imaging (including spectroscopy); X-rays (dysostoses or other bone abnormalities); ultrasound (enlarged liver/spleen)) • a VUS (variant of unknown significance) in a gene involved in metabolism
Exclusion criteria
Exclusion criteria: after discussion by the Solve the Unsolved team the patient is suspected to have: - a genetic condition for which there is a simpler and more cost-effective test available for diagnosis - a complex genetic disorder (caused by a combination of multiple genes and/or environmental influences) - a condition that is thought to be caused by factors that are non-genetic, such as infection, injury or toxic exposure • he/she is unable to follow the study protocol (e.g. additional blood samples)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Identification of a genetic variant and alignment with its biochemical and phenotypical abnormalities. | — |
Secondary
| Measure | Time frame |
|---|---|
| Evaluating the diagnostic yield of combined WES/WGS and omics techniques. | — |
Countries
Netherlands
Outcome results
None listed