Genetic Diagnosis in Inborn Errors of Metabolism

• Conditions: Metabolic Disease; Epilepsy; LHON; Epilepsy in Children; Motor Neuron Disease; Mitochondrial Diseases

• Registration Number: NCT06376279
• Lead Sponsor: Region Stockholm

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.

Study Timeline

• Study Start: 2008-04-29
• Status Verified: 2024-01
• Study First Submitted: 2024-01-29
• Study First Submitted QC: 2024-04-16
• Last Update Submitted: 2024-04-16
• Study First Posted: 2024-04-19
• Last Update Posted: 2024-04-19
• Primary Completion: 2030-12-31
• Study Completion: 2030-12-31

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 1000

Inclusion Criteria

• Medical inferral, suspicion metabolic disease incl epilepsy and their relatives

Exclusion Criteria

• Disease other than metabolic

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Genetic variant identification using NGS for diagnosis	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.