| 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. |
- Björkman, Kristoffer, et al.
(författare)
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Genotype-phenotype correlations in patients with complex I deficiency due to mutations in NDUFS1 and NDUFV1
- 2014
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Ingår i: Euromit 2014, 15-19 juni, Tampere, Finland.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Objectives: To study genotype-phenotype correlations in genes encoding complex I electron input module subunits. Materials and methods: We studied five patients with isolated complex I deficiency, three with NDUFS1 mutations and two with NDUFV1 mutations. A literature review of all reported cases of mutations in the affected genes was performed. Results: The literature review revealed pathological mutations in NDUFS1 for 18 patients in 17 families and correspondingly in NDUFV1 for 26 patients in 19 families. Unpublished clinical data for our five patients were added. Our study showed quite variable clinical courses; death before two years of age was seen in 41% of patients while 18% were alive at seven years. There was a significant difference between the NDUFS1 and NDUFV1 groups for clinical onset and life-span. Mutations in NDUFS1 were linked to a worse clinical course with earlier onset and earlier death. Conclusions: Genotype-phenotype correlations in patients with mutations affecting the genes that encode the electron input module of complex I vary, but patients with NDUFS1 mutation tend to have a worse clinical course than patients with NDUFV1 mutation. Identifying the mutations is of importance for accurate prognostic information and genetic counseling.
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| 6. |
- Krantz, Mattias, et al.
(författare)
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Parental experiences of having a child with CLN3 disease (juvenile Batten disease) and how these experiences relate to family resilience
- 2022
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Ingår i: Child: Care, Health and Development. - : Wiley. - 0305-1862 .- 1365-2214. ; 48:5, s. 842-851
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Tidskriftsartikel (refereegranskat)abstract
- Background: CLN3 disease is a neurodegenerative condition presenting in the first decade of life typically leading to death in the third decade. The earliest symptom is rapidly progressive visual impairment followed by intellectual and motor impairments, epilepsy and behavioural disturbances. There are limited data on how the condition affects the family system or the role of family resilience in paediatric neurodegenerative diseases. Methods: Semi-structured interviews were conducted with eight parents (five mothers and three fathers) of five children with CLN3. Interview questions focused on the experience of having a child with CLN3, its impact on the family system as well as the concept of family resilience. Data were analysed via thematic analysis. Results: The thematic analysis resulted in four main themes. The theme ‘recurring losses’ included the feeling of losing a healthy child, the child's loss of abilities and loss of relationships. The theme ‘disruption to the family system’ included that siblings could be ‘side-lined’, the potential negative impact on romantic relationships and difficulties finding time to oneself. The theme ‘Society is not developed for a progressive disease’ highlighted the difficulties parents faced with respect to contacts with the health and/or social insurance system. The paediatric health care system was seen as supportive, but the adult health care system was not seen as fit for the purpose. Regarding family resilience, parents felt that the disease forced them to reconsider what was important in life. Several parents described that they learned to value small moments of joy and create deep connections through involvement in family routines and rituals. Conclusions: CLN3 places a very significant burden on the family system including parental feelings of loss, impact on family relationships and lack of understanding within the health/social insurance systems. The concept of family resilience may be useful in understanding the experiences of families affected by paediatric neurodegenerative conditions.
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| 7. |
- Lehtonen, J. M., et al.
(författare)
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Diagnostic value of serum biomarkersFGF21andGDF15compared to muscle sample in mitochondrial disease
- 2021
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Ingår i: Journal of Inherited Metabolic Disease. - : Wiley. - 0141-8955 .- 1573-2665. ; 44:2, s. 469-480
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to compare the value of serum biomarkers, fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15), with histological analysis of muscle in the diagnosis of mitochondrial disease. We collected 194 serum samples from patients with a suspected or known mitochondrial disease. Biomarkers were analyzed blinded using enzyme-labeled immunosorbent assay. Clinical data were collected using a structured questionnaire. Only 39% of patients with genetically verified mitochondrial disease had mitochondrial pathology in their muscle histology. In contrast, biomarkers were elevated in 62% of patients with genetically verified mitochondrial disease. Those with both biomarkers elevated had a muscle manifesting disorder and a defect affecting mitochondrial DNA expression. If at least one of the biomarkers was induced and the patient had a myopathic disease, a mitochondrial DNA expression disease was the cause with 94% probability. Among patients with biomarker analysis and muscle biopsy taken <12 months apart, a mitochondrial disorder would have been identified in 70% with analysis of FGF21 and GDF15 compared to 50% of patients whom could have been identified with muscle biopsy alone. Muscle findings were nondiagnostic in 72% (children) and 45% (adults). Induction of FGF21 and GDF15 suggest a mitochondrial etiology as an underlying cause of a muscle manifesting disease. Normal biomarker values do not, however, rule out a mitochondrial disorder, especially if the disease does not manifest in muscle. We suggest that FGF21 and GDF15 together should be first-line diagnostic investigations in mitochondrial disease complementing muscle biopsy.
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| 8. |
- Michael, Eva, et al.
(författare)
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Long term treatment with ataluren-the Swedish experience
- 2021
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Ingår i: Bmc Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Ataluren is a relatively new treatment for male patients with Duchenne muscular dystrophy (DMD) due to a premature stop codon. Long-term longitudinal data as well as efficacy data on non-ambulant patients are still lacking. Here we present the results from a long-term follow-up study of all DMD patients treated with ataluren and followed at the Queen Silvia Children's Hospital in Gothenburg, Sweden, with focus on the evolution of patients' upper motor and respiratory function over time. Methods This is a retrospective longitudinal case-series study of all male DMD patients treated with ataluren and followed at the Queen Silvia Children's Hospital in Gothenburg, Sweden, since 2008. Results Our eleven patients had a median exposure to ataluren of 2312 days which is almost a fourfold higher than previous studies. Loss of ambulation occurred at a median age of 13.2 years. Patients who lost ambulation prior to 13.2 years of age had received ataluren for 5 years, whereas patients who continued to be ambulatory after 13.2 years of age had received ataluren for 6.5 years until loss of ambulation or last follow-up if still ambulatory. Four of six non ambulatory patients had Performance of the Upper Limb scores above the expected mean values over time. All but one patient maintained a pulmonary decline above the expected over time. All ambulatory patients increased in their predicted forced vital capacity (FVC) with 2.8 to 8.2% annually. Following loss of ambulation, 5 of 6 patients declined in predicted FVC (%), with annual rate of decline varying from 1.8 to 21.1%. The treatment was safe and well tolerated throughout the follow-up period. Conclusions This is the first study to present long-term cumulative treatment outcomes over a median period of 6.3 years on ataluren treatment. Our results indicate a delay in loss of ambulation, as well as a slower decline in FVC and upper limb motor function even after loss of ambulation. We suggest that treatment with ataluren should be initiated as soon as the diagnosis is confirmed, closely monitored and, in case of sustainable benefit, continued even after loss of ambulation.
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| 9. |
- Parasyri, M., et al.
(författare)
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Renal Phenotype in Mitochondrial Diseases: A Multicenter Study
- 2022
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Ingår i: Kidney Diseases. - : S. Karger AG. - 2296-9381 .- 2296-9357. ; 8:2
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Tidskriftsartikel (refereegranskat)abstract
- Aims: This study aimed to investigate associations between renal and extrarenal manifestations of mitochondrial diseases and their natural history as well as predictors of renal disease severity and overall disease outcome. The secondary aim was to generate a protocol of presymptomatic assessment and monitoring of renal function in patients with a defined mitochondrial disease. Methods: A multicenter, retrospective cohort study was performed by the Mitochondrial Clinical and Research Network (MCRN). Patients of any age with renal manifestations associated with a genetically verified mitochondrial disease were included from 8 expert European centers specializing in mitochondrial diseases: Gothenburg, Oulu, Copenhagen, Bergen, Helsinki, Stockholm, Rotterdam, and Barcelona. Results: Of the 36 patients included, two-thirds had mitochondrial DNA-associated disease. Renal manifestations were the first sign of mitochondrial disease in 19%, and renal involvement was first identified by laboratory tests in 57% of patients. Acute kidney injury occurred in 19% of patients and was the first sign of renal disease in the majority of these. The most common renal manifestation was chronic kidney disease (75% with stage 2 or greater), followed by tubulopathy (44.4%), the latter seen mostly among patients with single large-scale mitochondrial DNA deletions. Acute kidney injury and tubulopathy correlated with worse survival outcome. The most common findings on renal imaging were increased echogenicity and renal dysplasia/hypoplasia. Renal histology revealed focal segmental glomerulosclerosis, nephrocalcinosis, and nephronophthisis. Conclusion: Acute kidney injury is a distinct renal phenotype in patients with mitochondrial disease. Our results highlight the importance to recognize renal disease as a sign of an underlying mitochondrial disease. Acute kidney injury and tubulopathy are 2 distinct indicators of poor survival in patients with mitochondrial diseases.
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| 10. |
- Pennings, M., et al.
(författare)
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KIF1A variants are a frequent cause of autosomal dominant hereditary spastic paraplegia
- 2020
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 28
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Tidskriftsartikel (refereegranskat)abstract
- Variants in the KIF1A gene can cause autosomal recessive spastic paraplegia 30, autosomal recessive hereditary sensory neuropathy, or autosomal (de novo) dominant mental retardation type 9. More recently, variants in KIF1A have also been described in a few cases with autosomal dominant spastic paraplegia. Here, we describe 20 KIF1A variants in 24 patients from a clinical exome sequencing cohort of 347 individuals with a mostly ‘pure’ spastic paraplegia. In these patients, spastic paraplegia was slowly progressive and mostly pure, but with a highly variable disease onset (0–57 years). Segregation analyses showed a de novo occurrence in seven cases, and a dominant inheritance pattern in 11 families. The motor domain of KIF1A is a hotspot for disease causing variants in autosomal dominant spastic paraplegia, similar to mental retardation type 9 and recessive spastic paraplegia type 30. However, unlike these allelic disorders, dominant spastic paraplegia was also caused by loss-of-function variants outside this domain in six families. Finally, three missense variants were outside the motor domain and need further characterization. In conclusion, KIF1A variants are a frequent cause of autosomal dominant spastic paraplegia in our cohort (6–7%). The identification of KIF1A loss-of-function variants suggests haploinsufficiency as a possible mechanism in autosomal dominant spastic paraplegia. © 2019, The Author(s).
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