## Protocol Section
### Identification Module
**NCT ID:** NCT06376279

**Brief Title:** Genetic Diagnosis in Inborn Errors of Metabolism

**Official Title:** Genetisk Diagnostik Vid medfödda Metabola Sjukdomar

#### Organization Study ID Info
**ID:** 2008/351-31
#### Organization
**Class:** OTHER_GOV
**Full Name:** Region Stockholm
### Status Module
#### Completion Date
**Date:** 2030-12-31

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-04-19

**Type:** ACTUAL

**Last Update Submit Date:** 2024-04-16

**Overall Status:** ENROLLING_BY_INVITATION

#### Primary Completion Date
**Date:** 2030-12-31

**Type:** ESTIMATED

#### Start Date
**Date:** 2008-04-29

**Type:** ACTUAL

**Status Verified Date:** 2024-01

#### Study First Post Date
**Date:** 2024-04-19
**Type:** ACTUAL
**Study First Submit Date:** 2024-01-29
**Study First Submit QC Date:** 2024-04-16
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** Karolinska Institutet

#### Lead Sponsor

**Class:** OTHER_GOV

**Name:** Region Stockholm

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**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.

### Conditions Module

**Conditions:**

- Metabolic Disease

- Mitochondrial Diseases

- Epilepsy in Children

- Epilepsy

- LHON

- Motor Neuron Disease

### Design Module

#### Bio Spec

**Description:** Blood, Muscle biopsy, skin biopsy, fibroblasts, urine

**Retention:** SAMPLES_WITH_DNA

#### Design Info

**Observational Model:** COHORT

**Time Perspective:** CROSS_SECTIONAL

#### Enrollment Info

**Count:** 1000

**Type:** ESTIMATED

**Study Type:** OBSERVATIONAL

### Arms Interventions Module

### Interventions

#### Intervention 1

**Description:** Data from IEM-inborn error of metabolism cohort of individuals

**Name:** IEM-EP

**Type:** GENETIC

### Outcomes Module

#### Primary Outcomes

**Description:** 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.

**Measure:** Genetic variant identification using NGS for diagnosis

**Time Frame:** Through study completion, an average of 1 year.

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

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

Exclusion Criteria:

* Disease other than metabolic

**Healthy Volunteers:** True

**Sampling Method:** NON_PROBABILITY_SAMPLE

**Sex:** ALL

**Standard Ages:**

- CHILD

- ADULT

- OLDER_ADULT

**Study Population:** Inborn errors of metabolism, a group of around one thousand different monogenic diseases with a wide spectrum of presentation.

### Contacts Locations Module

#### Overall Officials

**Official 1:**

**Affiliation:** Karolinska University Hospital, Karolinska Institutet

**Name:** Anna Wedell

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000001927

- Term: Brain Diseases

- ID: D000002493

- Term: Central Nervous System Diseases

- ID: D000009422

- Term: Nervous System Diseases

- ID: D000019636

- Term: Neurodegenerative Diseases

- ID: D000009468

- Term: Neuromuscular Diseases

- ID: D000013118

- Term: Spinal Cord Diseases

- ID: D000057177

- Term: TDP-43 Proteinopathies

- ID: D000057165

- Term: Proteostasis Deficiencies

### Condition Browse Module - Browse Branches

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC18

- Name: Nutritional and Metabolic Diseases

- Abbrev: BC16

- Name: Diseases and Abnormalities at or Before Birth

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M18879

- Name: Motor Neuron Disease

- Relevance: HIGH

- As Found: Motor Neuron Disease

- ID: M4024

- Name: Amyotrophic Lateral Sclerosis

- Relevance: HIGH

- As Found: Motor Neuron Disease

- ID: M7983

- Name: Epilepsy

- Relevance: HIGH

- As Found: Epilepsy

- ID: M11639

- Name: Metabolic Diseases

- Relevance: HIGH

- As Found: Metabolic Diseases

- ID: M23341

- Name: Mitochondrial Diseases

- Relevance: HIGH

- As Found: Mitochondrial Disease

- ID: M11641

- Name: Metabolism, Inborn Errors

- Relevance: LOW

- As Found: Unknown

- ID: M15415

- Name: Sclerosis

- Relevance: LOW

- As Found: Unknown

- ID: M5204

- Name: Brain Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5742

- Name: Central Nervous System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M21558

- Name: Neurodegenerative Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12411

- Name: Neuromuscular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M15915

- Name: Spinal Cord Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M28759

- Name: TDP-43 Proteinopathies

- Relevance: LOW

- As Found: Unknown

- ID: M28747

- Name: Proteostasis Deficiencies

- Relevance: LOW

- As Found: Unknown

- ID: T349

- Name: Amyotrophic Lateral Sclerosis

- Relevance: HIGH

- As Found: Motor Neuron Disease

- ID: T4699

- Name: Primary Lateral Sclerosis

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000004827

- Term: Epilepsy

- ID: D000016472

- Term: Motor Neuron Disease

- ID: D000000690

- Term: Amyotrophic Lateral Sclerosis

- ID: D000008659

- Term: Metabolic Diseases

- ID: D000028361

- Term: Mitochondrial Diseases

### Misc Info Module

- Version Holder: 2024-05-24
