| 1. |
- Andersson Grönlund, Marita, 1959-, et al.
(författare)
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Ophthalmologic involvement in Leigh syndrome
- 2017
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Ingår i: Acta Ophthalmologica. - : John Wiley & Sons. - 1755-375X .- 1755-3768. ; 95:1
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Tidskriftsartikel (refereegranskat)
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| 2. |
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| 3. |
- Björkman, Kristoffer, et al.
(författare)
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Broad phenotypic variability in patients with complex I deficiency due to mutations in NDUFS1 and NDUFV1.
- 2015
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Ingår i: Mitochondrion. - : Elsevier BV. - 1872-8278 .- 1567-7249. ; 21, s. 33-40
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Tidskriftsartikel (refereegranskat)abstract
- We report clinical, metabolic, genetic and neuroradiological findings in five patients from three different families with isolated complex I deficiency. Genetic analysis revealed mutations in NDUFS1 in three patients and in NDUFV1 in two patients. Four of the mutations are novel and affect amino acid residues that either are invariant among species or conserved in their properties. The presented clinical courses are characterized by leukoencephalopathy or early death and expand the already heterogeneous phenotypic spectrum. A literature review was performed, showing that patients with mutations in NDUFS1 in general have a worse prognosis than patients with mutations in NDUFV1.
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| 4. |
- Roos, Sara, 1979, et al.
(författare)
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Mitochondrial complex IV deficiency caused by a novel frameshift variant in MT-CO2 associated with myopathy and perturbed acylcarnitine profile
- 2019
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 27:2, s. 331-335
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Tidskriftsartikel (refereegranskat)abstract
- Mitochondrial myopathies are a heterogeneous group of disorders associated with a wide range of clinical phenotypes. We present a 16-year-old girl with a history of exercise intolerance since childhood. Acylcarnitine species suggestive of multiple acyl-CoA dehydrogenase deficiency were found in serum, however genetic analysis did not reveal variants in genes associated with this disorder. Biochemical analyses of skeletal muscle mitochondria revealed an isolated and extremely low activity of cytochrome c oxidase (COX). This finding was confirmed by enzyme histochemistry, which demonstrated an almost complete absence of fibers with normal COX activity. Whole-exome sequencing revealed a single base-pair deletion (m.8088delT) in MT-CO2, which encodes subunit 2 of COX, resulting in a premature stop codon. Restriction fragment length polymorphism-analysis confirmed mtDNA heteroplasmy with high mutant load in skeletal muscle, the only clinically affected tissue, but low levels in other investigated tissues. Single muscle fiber analysis showed segregation of the mutant genotype with respiratory chain dysfunction. Immuno-histochemical studies indicated that the truncating variant in COX2 has an inhibitory effect on the assembly of the COX holoenzyme.
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| 5. |
- Sofou, Kalliopi, et al.
(författare)
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Cerebrospinal fluid neurofilament light is associated with survival in mitochondrial disease patients
- 2019
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Ingår i: Mitochondrion. - : Elsevier BV. - 1567-7249 .- 1872-8278. ; 46, s. 228-235
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Tidskriftsartikel (refereegranskat)abstract
- We studied the biomarker patterns related to axonal injury, astrogliosis and amyloid metabolism in cerebrospinal fluid (CSF) of children and adolescents with mitochondrial encephalopathy and identified correlations with phenotype and survival outcome. Forty-six pediatric patients with genetically verified mitochondrial encephalopathy and twenty-two controls investigated at the Queen Silvia Children's Hospital, Sweden, were included. CSF lactate and neurofilament light (NF-L) were significantly increased in patients with mitochondrial encephalopathy compared to controls. Elevated CSF NF-L was associated with abnormal brain MRI and poorer survival. We suggest that CSF NF-L may be used in both clinical and research settings for monitoring the neurodegenerative process in mitochondrial disease.
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| 6. |
- Sofou, Kalliopi, et al.
(författare)
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Ketogenic diet in pyruvate dehydrogenase complex deficiency: short- and long-term outcomes.
- 2017
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Ingår i: Journal of inherited metabolic disease. - : Wiley. - 1573-2665 .- 0141-8955. ; 40:2, s. 237-245
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Tidskriftsartikel (refereegranskat)abstract
- Our aime was to study the short- and long-term effects of ketogenic diet on the disease course and disease-related outcomes in patients with pyruvate dehydrogenase complex deficiency, the metabolic factors implicated in treatment outcomes, and potential safety and compliance issues.Pediatric patients diagnosed with pyruvate dehydrogenase complex deficiency in Sweden and treated with ketogenic diet were evaluated. Study assessments at specific time points included developmental and neurocognitive testing, patient log books, and investigator and parental questionnaires. A systematic literature review was also performed.Nineteen patients were assessed, the majority having prenatal disease onset. Patients were treated with ketogenic diet for a median of 2.9years. All patients alive at the time of data registration at a median age of 6years. The treatment had a positive effect mainly in the areas of epilepsy, ataxia, sleep disturbance, speech/language development, social functioning, and frequency of hospitalizations. It was also safe-except in one patient who discontinued because of acute pancreatitis. The median plasma concentration of ketone bodies (3-hydroxybutyric acid) was 3.3mmol/l. Poor dietary compliance was associated with relapsing ataxia and stagnation of motor and neurocognitive development. Results of neurocognitive testing are reported for 12 of 19 patients.Ketogenic diet was an effective and safe treatment for the majority of patients. Treatment effect was mainly determined by disease phenotype and attainment and maintenance of ketosis.
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| 7. |
- Sofou, Kalliopi, et al.
(författare)
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Phenotype-genotype correlations in Leigh syndrome: new insights from a multicentre study of 96 patients.
- 2018
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Ingår i: Journal of medical genetics. - : BMJ. - 1468-6244 .- 0022-2593. ; 55:1, s. 21-27
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Tidskriftsartikel (refereegranskat)abstract
- Leigh syndrome is a phenotypically and genetically heterogeneous mitochondrial disorder. While some genetic defects are associated with well-described phenotypes, phenotype-genotype correlations in Leigh syndrome are not fully explored.We aimed to identify phenotype-genotype correlations in Leigh syndrome in a large cohort of systematically evaluated patients.We studied 96 patients with genetically confirmed Leigh syndrome diagnosed and followed in eight European centres specialising in mitochondrial diseases.We found that ataxia, ophthalmoplegia and cardiomyopathy were more prevalent among patients with mitochondrial DNA defects. Patients with mutations in MT-ND and NDUF genes with complex I deficiency shared common phenotypic features, such as early development of central nervous system disease, followed by high occurrence of cardiac and ocular manifestations. The cerebral cortex was affected in patients with NDUF mutations significantly more often than the rest of the cohort. Patients with the m.8993T>Gmutation in MT-ATP6 gene had more severe clinical and radiological manifestations and poorer disease outcome compared with patients with the m.8993T>Cmutation.Our study provides new insights into phenotype-genotype correlations in Leigh syndrome and particularly in patients with complex I deficiency and with defects in the mitochondrial ATP synthase.
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| 8. |
- Sofou, Kalliopi, et al.
(författare)
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Prenatal onset of mitochondrial disease is associated with sideroflexin 4 deficiency
- 2019
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Ingår i: Mitochondrion. - : Elsevier BV. - 1567-7249. ; 47, s. 76-81
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Tidskriftsartikel (refereegranskat)abstract
- Prenatal onset of mitochondrial disease has been described in two cases with recessive mutations in the sideroflexin 4 gene (SFXN4). We present a third case with complex I deficiency associated with novel mutations in SFXN4. Our patient presented with intrauterine growth retardation, neonatal lactic acidosis, and developed macrocytic anemia and optic nerve hypoplasia. Muscle mitochondrial investigations revealed ultrastructural abnormalities, severe deficiency of complex I enzyme activity, and loss of subunit proteins. Whole-exome sequencing revealed bi-allelic SFXN4 mutations: a 1-base deletion, c.969delG, leading to frameshift and a premature stop codon, p.(G1n323Hisfs*20), and a stop-loss mutation in the C-terminal region, c.1012 T > C; p. (*388Glnext2), resulting in elongation of the protein by two amino acids. Expression analysis of mRNA from muscle showed loss of SFXN4 transcripts.
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| 9. |
- Sofou, Kalliopi, et al.
(författare)
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SITUPS: a new tool for oral case presentation in the paediatric emergency department
- 2019
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 108:8, s. 1467-1474
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Tidskriftsartikel (refereegranskat)abstract
- Aim We developed a new case presentation technique, SITUPS, and studied its impact on the patient presentations by medical students at a paediatric emergency department. The students' opinions about the usefulness of the technique were also assessed. Methods The students saw patients both before and after introduction to SITUPS. Their presentations were analysed by the clinical instructor using a student assessment form. The students filled in a 15-item questionnaire about their opinion of SITUPS as a learning tool. Results Twenty-eight students were evaluated both without and with SITUPS in a total of 78 presentations. Using SITUPS, the students gave more complete case presentations without increasing the presentation time. The main areas of improvement were discussing differential diagnoses, proposing a management plan, and identifying where they lacked knowledge and needed to ask the instructor questions. The students found SITUPS particularly helpful in identifying family and social issues of significance, thinking of relevant questions to ask the patient and the family, and thinking through differential diagnoses. Conclusion We propose a new case presentation technique, SITUPS, for use at the paediatric emergency department. With the help of SITUPS, the medical students gave more complete case presentations in a time-effective manner.
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| 10. |
- Sofou, Kalliopi, et al.
(författare)
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Whole exome sequencing reveals mutations in NARS2 and PARS2, encoding the mitochondrial asparaginyl-tRNA synthetase and prolyl-tRNA synthetase, in patients with Alpers syndrome.
- 2015
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Ingår i: Molecular genetics & genomic medicine. - : Wiley. - 2324-9269. ; 3:1, s. 59-68
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Tidskriftsartikel (refereegranskat)abstract
- Alpers syndrome is a progressive neurodegenerative disorder that presents in infancy or early childhood and is characterized by diffuse degeneration of cerebral gray matter. While mutations in POLG1, the gene encoding the gamma subunit of the mitochondrial DNA polymerase, have been associated with Alpers syndrome with liver failure (Alpers-Huttenlocher syndrome), the genetic cause of Alpers syndrome in most patients remains unidentified. With whole exome sequencing we have identified mutations in NARS2 and PARS2, the genes encoding the mitochondrial asparaginyl-and prolyl-tRNA synthetases, in two patients with Alpers syndrome. One of the patients was homozygous for a missense mutation (c.641C>T, p.P214L) in NARS2. The affected residue is predicted to be located in the stem of a loop that participates in dimer interaction. The other patient was compound heterozygous for a one base insertion (c.1130dupC, p.K378 fs*1) that creates a premature stop codon and a missense mutation (c.836C>T, p.S279L) located in a conserved motif of unknown function in PARS2. This report links for the first time mutations in these genes to human disease in general and to Alpers syndrome in particular.
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