Genetisk Diagnostik Vid medfödda Metabola Sjukdomar
Overview
- Phase
- N/A
- Intervention
- Not specified
- Conditions
- Metabolic Disease
- Sponsor
- Region Stockholm
- Enrollment
- 1000
- Primary Endpoint
- Genetic variant identification using NGS for diagnosis
- Status
- Enrolling by Invitation
- Last Updated
- 2 years ago
Overview
Brief Summary
Inborn Errors of metabolism comprise a large number of rare conditions with a collective incidence of around 1/2000 newborns. Many disorders are treatable provided that a correct diagnosis can be established in time, and for many diseases novel therapies are being developed. Without treatment, many of the conditions result in early death or severe irreversible handicaps.
The Centre for Inherited Metabolic Diseases, CMMS at Karolinska university hospital, is an integrated expert center where clinical specialists work closely together with experts in laboratory medicine, combining clinical genetics, clinical chemistry, pediatrics, neurology, and endocrinology. The center serves the whole Swedish population with diagnostics and expert advice on IEM and has a broad arsenal of biochemical investigations designed to detect defects in intermediary metabolism.
Detailed Description
Approximately one in two thousand infants is born with a metabolic disorder that often leads to brain damage. By means of high-tech genetic mapping using whole genome sequencing (WGS), we have discovered the molecular foundations for several of these diseases. For investigation of mitochondrial diseases, mitochondria are isolated from muscle biopsies for analysis of ATP production using a range of substrate combinations, determination of activities of respiratory chain complexes, and analysis of nuclear and mitochondrial DNA. The center also performs the national neonatal screening program, currently comprising 26 treatable diseases. Dried blood spot samples (DBS) are stored in the phenylketonuria (PKU) biobank, currently (2024 january) holding around 4.9 million of Sweden's 10.6 million inhabitants. Many metabolic disorders, however, lack effective counter-measures.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Medical inferral, suspicion metabolic disease incl epilepsy and their relatives
Exclusion Criteria
- •Disease other than metabolic
Outcomes
Primary Outcomes
Genetic variant identification using NGS for diagnosis
Time Frame: Through study completion, an average of 1 year.
Variant identification in patients investigated at our clinic, Centre for inherited metabolic diseases, is an ongoing clinical activity. In many cases, if no variant is identified with NGS (Next Genenation Sequencing) using WGS, additional methods are used such as transcriptomics, proteomics and different cellmodels. More than 400 patients are investigated yearly with NGS/WGS in our clinic.