Genetic Diagnosis in Inborn Errors of Metabolism

Epilepsy Clinical Trial

Official title:

Genetisk Diagnostik Vid medfödda Metabola Sjukdomar

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT06376279
• Other study ID #: 2008/351-31
• Status: Enrolling by invitation
• Start date: April 29, 2008
• Est. completion date: December 31, 2030

Study information

• Verified date: January 2024
• Source: Region Stockholm
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 1000
• Est. completion date: December 31, 2030
• Est. primary completion date: December 31, 2030
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

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

Exclusion Criteria:

• Disease other than metabolic

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Epilepsy
• Epilepsy in Children
• LHON
• Metabolic Disease
• Metabolic Diseases
• Mitochondrial Diseases
• Motor Neuron Disease

Intervention

Genetic:
• IEM-EP
Data from IEM-inborn error of metabolism cohort of individuals

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Region Stockholm	Karolinska Institutet

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Genetic variant identification using NGS for diagnosis	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.	Through study completion, an average of 1 year.