A5046297705- Metabolism and Genetic Disorders
- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
- Genomics and Rare Diseases
- Lysosomal Storage Disorders Research
- Genomic variations and chromosomal abnormalities
- Epilepsy research and treatment
- Amino Acid Enzymes and Metabolism
- Biomedical and Chemical Research
- Biochemical Acid Research Studies
- Eicosanoids and Hypertension Pharmacology
- RNA modifications and cancer
- Genetic factors in colorectal cancer
- Chromium effects and bioremediation
- Pharmacology and Obesity Treatment
- Electrolyte and hormonal disorders
- Adrenal Hormones and Disorders
- Calcium signaling and nucleotide metabolism
- Glycogen Storage Diseases and Myoclonus
- Hormonal Regulation and Hypertension
- Biomedical Research and Pathophysiology
- Neurological Disorders and Treatments
- Chemical Reactions and Isotopes
- Pharmacovigilance and Adverse Drug Reactions
- Medical and Biological Sciences
Karolinska University Hospital
2015-2024
Karolinska Institutet
2015-2024
Leigh syndrome is a progressive neurodegenerative disorder, associated with primary or secondary dysfunction of the mitochondrial oxidative phosphorylation. Despite fact that most common phenotype disorders in children, longitudinal natural history data missing. This study was undertaken to assess phenotypic and genotypic spectrum patients syndrome, characterise clinical course identify predictors survival large cohort patients.This retrospective have been followed at eight centers...
Abstract Background We report the findings from 4437 individuals (3219 patients and 1218 relatives) who have been analyzed by whole genome sequencing (WGS) at Genomic Medicine Center Karolinska-Rare Diseases (GMCK-RD) since mid-2015. GMCK-RD represents a long-term collaborative initiative between Karolinska University Hospital Science for Life Laboratory to establish advanced, genomics-based diagnostics in Stockholm healthcare setting. Methods Our analysis covers detection interpretation of...
The mitochondrial aspartate-glutamate carrier isoform 1 (AGC1), specific to neurons and muscle, supplies aspartate the cytosol and, as a component of malate-aspartate shuttle, enables oxidation cytosolic NADH, thought be important in providing energy for central nervous system. We describe AGC1 deficiency, novel syndrome characterized by arrested psychomotor development, hypotonia, seizures child with homozygous missense mutation solute family 25, member 12, gene SLC25A12, which encodes...
<h3>Background</h3> Coenzyme Q is an essential mitochondrial electron carrier, redox cofactor and a potent antioxidant in the majority of cellular membranes. deficiency has been associated with range metabolic diseases, as well some drug treatments ageing. <h3>Methods</h3> We used whole exome sequencing (WES) to investigate patients inherited diseases applied novel ultra-pressure liquid chromatography—mass spectrometry approach measure coenzyme patient samples. <h3>Results</h3> identified...
Background Leigh syndrome is a phenotypically and genetically heterogeneous mitochondrial disorder. While some genetic defects are associated with well-described phenotypes, phenotype-genotype correlations in not fully explored. Objective We aimed to identify large cohort of systematically evaluated patients. Methods studied 96 patients confirmed diagnosed followed eight European centres specialising diseases. Results found that ataxia, ophthalmoplegia cardiomyopathy were more prevalent...
Variants in POLG are one of the most common causes inherited mitochondrial disease. Phenotypic classification disease has evolved haphazardly making it complicated and difficult to implement everyday clinical practise. The aim our study was simplify facilitate better recognition.A multinational, retrospective using data from 155 patients with variants recruited seven European countries.We describe spectrum features associated largest known cohort patients. While clearly form a continuum,...
Objective 3‐Methylglutaconic aciduria, dystonia–deafness, hepatopathy, encephalopathy, Leigh‐like syndrome (MEGDHEL) is caused by biallelic variants in SERAC1 . Methods This multicenter study addressed the course of disease for each organ system. Metabolic, neuroradiological, and genetic findings are reported. Results Sixty‐seven individuals (39 previously unreported) from 59 families were included (age range = 5 days–33.4 years, median age 9 years). A total 41 different identified,...
Massively parallel DNA sequencing (MPS) has the potential to revolutionize diagnostics, in particular for monogenic disorders. Inborn errors of metabolism (IEM) constitute a large group disorders with highly variable clinical presentation, often acute, nonspecific initial symptoms. In many cases irreversible damage can be reduced by initiation specific treatment, provided that correct molecular diagnosis rapidly obtained. MPS thus significantly improve both diagnostics and outcome affected...
We aimed to provide a detailed phenotypic description of status epilepticus (SE) in large cohort patients with POLG disease and identify prognostic biomarkers improve the management this life-threatening condition. In multinational, retrospective study data on from seven European countries, we identified those who had SE. The age SE onset, accompanying clinical, laboratory, imaging genetic findings were analysed. One hundred ninety-five genetically confirmed recruited, whom 67% (130/194)...
Mitochondrial complex I deficiency is the most common defect of OXPHOS system. We report a patient from consanguineous parents with expressed in skin fibroblasts. Homozygosity mapping revealed several homozygous regions candidate genes, including gene encoding an assembly factor for I, NDUFAF2. Screening this on genomic DNA stop-codon resulting truncation protein at position 38. The mutation causes severely reduced activity and disturbed I. A baculovirus containing GFP-tagged wild-type...
Abstract The objective of this study was to investigate clinical, biochemical, and genetic features in 7 probands (a total 11 patients) with nicotine‐amide adenine dinucleotide (NADH) dehydrogenase (complex I) deficiency. We screened the mitochondrial DNA for mutations found pathogenic complex I genes (mitochondrial NADH subunit (MTND) genes) three probands. 10191T〉C mutation MTND3 14487T〉C MTND6 were present two Leigh's‐like Leigh's syndrome, respectively. Four siblings a syndrome...
To follow-up six children with severe mucopolysaccharidosis type IH, Hurler syndrome, who were treated before 24 months of age haematopoietic stem cell transplantation.In Sweden, during the last 10-year period, consecutive born mucopolysaccharidoses IH have been successfully transplanted using matched unrelated donors between ages 11 and (mean 18 months). Three received intravenous enzyme replacement therapy once a week, from diagnosis until engraftment their bone marrow.Two developed...
Pediatric movement disorders are still a diagnostic challenge, as many patients remain without (genetic) diagnosis. Magnetic resonance imaging (MRI) pattern recognition can lead to the MEGDEL syndrome (3-<u>Me</u>thyl<u>G</u>lutaconic aciduria, <u>D</u>eafness, <u>E</u>ncephalopathy, <u>L</u>eigh-like MIM #614739) is clinically and biochemically highly distinctive dystonia deafness accompanied by 3-methylglutaconic severe developmental delay, progressive spasticity. Mutations found in...
Abstract Objective To delineate the full phenotypic spectrum of BCS1L‐ related disease, provide better understanding genotype–phenotype correlations and identify reliable prognostic disease markers. Methods We performed a retrospective multinational cohort study previously unpublished patients followed in 15 centres from 10 countries. Patients with confirmed biallelic pathogenic BCS1L variants were considered eligible. Clinical, laboratory, neuroimaging genetic data analysed. stratified into...
Abstract The vacuolar H+-ATPase is an enzymatic complex that functions in ATP-dependent manner to pump protons across membranes and acidify organelles, thereby creating the proton/pH gradient required for membrane trafficking by several different types of transporters. We describe heterozygous point variants ATP6V0C, encoding c-subunit bound integral domain H+-ATPase, 27 patients with neurodevelopmental abnormalities or without epilepsy. Corpus callosum hypoplasia cardiac were also present...
The vast clinical and radiological spectrum of pyruvate dehydrogenase complex (PDHc) deficiency continues to pose challenges both in diagnostics disease monitoring. Prompt diagnosis is important enable early initiation ketogenic diet. patients were recruited from an ongoing population-based study Sweden. All with a genetically confirmed who had been investigated MRI the brain included. Repeated investigations assessed evolution changes. Sixty-two performed 34 (23 females). genetic cause was...
Muscle weakness and exercise intolerance are hallmark symptoms in mitochondrial disorders. Little is known about the mechanisms leading to impaired skeletal muscle function ultimately these patients. In a mouse model of lethal myopathy, muscle-specific Tfam knock-out (KO) mouse, we previously demonstrated an excessive Ca2+ uptake isolated fibers that could be inhibited by cyclophilin D (CypD) inhibitor, cyclosporine A (CsA). Here show KO mice have increased CypD levels, demonstrate this...