Status:
COMPLETED
Zoektocht Naar Erfelijke MetaBole Aandoening (Dutch)/ Solve The Unsolved (English)
Lead Sponsor:
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Collaborating Sponsors:
Stichting Metakids
Conditions:
Inherited Metabolic Disorders
Eligibility:
All Genders
Phase:
NA
Brief Summary
The goal of this clinical trial is to integrate genomic (WES/WGS) and other -omics technologies in order to find the genetic causes, in 500 patients (children and adults) with an unexplained metabolic...
Detailed Description
Rationale: Inborn Errors of Metabolism (IEM) are monogenic conditions in which the impairment of a biochemical pathway is intrinsic to the pathophysiology of the disease. Organ dysfunction results fro...
Eligibility Criteria
Inclusion
- Patients 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):
- Energy deficiency: neurological (repeated rhabdomyolysis, verified exercise intolerance, neuropathy, myopathy, ataxia), ophthalmological (retinitis pigmentosa (RP)), otological (hearing loss, deafness), endocrine (hypoparathyroidism, hypoglycemia) Intoxication: neurological (encephalopathy, regression, movement disorder, psychiatric symptoms), ophthalmological (lens luxation), organic (liver and kidney function abnormalities) Storage: neurological (regression, psychiatric symptoms), ophthalmological (cataract/corneal clouding), skin (angiokeratomas), blood (cytopenias), organic (hepatosplenomegaly, cardiac hypertrophy, skeletal abnormalities, short stature, coarse facial features, umbilical/inguinal hernia)
- 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 indicative of a metabolic deficiency (e.g. respiratory chain complex analysis)
- organ dysfunction (e.g. liver or kidney failure)
- an abnormal clinical function test (protein loading test, fasting test, meal test, validated exercise test, non-ischaemic underarm test)
- 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
- AND no diagnosis despite extensive clinical, metabolic and genetic investigations
- SNP-array/array-CGH: inconclusive results
- metabolic screening according to up to date clinical protocols: inconclusive results
- WES (open or gene panel): no class 4 or 5 variants in a known (OMIM annotated) disease related gene that can fully explain the phenotype of the patient
Exclusion
- A patient will be excluded from participation in this study if:
- after discussion by the ZOEMBA team (see Methods) he/she 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)
Key Trial Info
Start Date :
December 10 2019
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
December 31 2021
Estimated Enrollment :
334 Patients enrolled
Trial Details
Trial ID
NCT06200142
Start Date
December 10 2019
End Date
December 31 2021
Last Update
January 10 2024
Active Locations (1)
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1
Amsterdam UMC
Amsterdam, Netherlands