| 1. |
- Savvidou, Antri, et al.
(författare)
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Novel imaging findings in pyruvate dehydrogenase complex (PDHc) deficiency—Results from a nationwide population-based study
- 2022
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Ingår i: Journal of Inherited Metabolic Disease. - : Wiley. - 0141-8955 .- 1573-2665. ; 45:2, s. 248-263
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Tidskriftsartikel (refereegranskat)abstract
- The vast clinical and radiological spectrum of pyruvate dehydrogenase complex (PDHc) deficiency continues to pose challenges both in diagnostics and disease monitoring. Prompt diagnosis is important to enable early initiation of ketogenic diet. The patients were recruited from an ongoing population-based study in Sweden. All patients with a genetically confirmed diagnosis who had been investigated with an MRI of the brain were included. Repeated investigations were assessed to study the evolution of the MRI changes. Sixty-two MRI investigations had been performed in 34 patients (23 females). The genetic cause was mutations in PDHA1 in 29, PDHX and DLAT in 2 each, and PDHB in 1. The lesions were prenatal developmental in 16, prenatal clastic in 18, and postnatal clastic in 15 individuals. Leigh-like lesions with predominant involvement of globus pallidus were present in 12, while leukoencephalopathy was present in 6 and stroke-like lesions in 3 individuals. A combination of prenatal developmental and clastic lesions was present in 15 individuals. In addition, one male with PDHA1 also had postnatal clastic lesions. The most common lesions found in our study were agenesis or hypoplasia of corpus callosum, ventriculomegaly, or Leigh-like lesions. Furthermore, we describe a broad spectrum of other MRI changes that include leukoencephalopathy and stroke-like lesions. We argue that a novel important clue, suggesting the possibility of PDHc deficiency on MRI scans, is the simultaneous presence of multiple lesions on MRI that have occurred during different phases of brain development.
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| 2. |
- 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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| 3. |
- Szakacs, Attila, et al.
(författare)
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A population-based and case-controlled study of children and adolescents with narcolepsy: Health-related quality of life, adaptive behavior and parental stress
- 2019
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Ingår i: European Journal of Paediatric Neurology. - : Elsevier BV. - 1090-3798. ; 23:2, s. 288-295
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate health-related quality of life (HrQoL) and adaptive behavior in young people with narcolepsy and stress among their parents. Methods: In a cross-sectional exploratory quantitative study design, 37 young people with narcolepsy (8-20 years of age) and their parents were recruited. Thirty-one had post-H1N1 vaccination-related narcolepsy (PHV) and six had narcolepsy not related to PHV (nPHV). In addition, 40 age- and gender-matched controls (aged 5-20 years) were recruited. Results: Thirty-one patients completed the generic HrQoL questionnaire KIDSCREEN and the disease-specific NARQoL-21. HrQoL was found to be significantly diminished in all domains in the PHV group (p = 0.001) and in the School/Concentration domain (p = 0.004) in the nPHV group compared to age- and gender-matched controls. The Adaptive Behavior Assessment System was completed by parents of 32 patients. They rated their children significantly lower in the General adaptive composite (p = 0.026) and the Conceptual (p = 0.050) and Social composite scores (p = 0.001) compared with reference data on healthy Swedish children's and young people's adaptive behavior. Parents of 36 patients filled in the 36-item short form of the Parenting Stress Index questionnaire. They rated significantly higher Total stress, Parent-child dysfunctional interaction, and Difficult child scores compared with parents of controls (p = 0.001, p = 0.005, p < 0.001). Conclusions: Children with narcolepsy have diminished HrQoL compared with controls. Parents of children with narcolepsy experience impaired adaptive behavior in their children and high levels of parenting stress. Identifying the contributory factors is necessary, and early intervention is crucial in order to improve the HrQoL of these children and their families. (C) 2019 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
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| 4. |
- Szakacs, Attila, et al.
(författare)
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Endocrine and metabolic aspects of narcolepsy type 1 in children
- 2021
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Ingår i: European Journal of Paediatric Neurology. - : Elsevier BV. - 1090-3798. ; 33, s. 68-74
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Tidskriftsartikel (refereegranskat)abstract
- Study objectives: To study whether the onset of narcolepsy type 1 (NT1) in children and adolescents affects BMI, specific metabolic risk factors, the onset of puberty, longitudinal growth or other endocrine functions. Methods: A population-based study, comprising 34 patients, was performed with a clinical evaluation, an assessment of puberty and growth, actigraphy and blood samples at fasting, from patients and controls, to evaluate pituitary function, growth factors, thyroid gland, gonads, insulin sensitivity, appetite regulation and blood lipids. Results: In the post-H1N1 vaccination (PHV) narcolepsy group, the median BMI SDS was higher 6-12 months after the onset of narcolepsy (p < 0.01), but it was no different 10 years after the onset of narcolepsy (p = 0.91), compared with 12-24 months before the onset of narcolepsy. There was a correlation between an increase in BMI and a decrease in total energy expenditure (R =-0.74). In the nPHV group, weight and BMI changes were smaller and no significant changes were recorded. Early puberty was more common in patients with puberty onset after narcolepsy onset (n = 16/19) compared with patients with puberty onset before narcolepsy onset (n = 3/11, p = 0.02). There was no significant change in height SDS during the studied period. Although they were within normal ranges, both median HDL and median TSH levels were significantly lower in NT1 patients, compared with controls. Conclusions: We found a high prevalence of large BMI gain in the period immediately after the onset of narcolepsy, which had almost normalized at the long-term follow-up. The onset of narcolepsy led to early puberty in both sexes. Linear growth was not affected. We did not find any strong indicators of metabolic disturbances. (c) 2021 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
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| 6. |
- Örlén, Hanna, et al.
(författare)
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SPG11 mutations cause Kjellin syndrome, a hereditary spastic paraplegia with thin corpus callosum and central retinal degeneration.
- 2009
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Ingår i: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics. - : Wiley. - 1552-485X .- 1552-4841. ; 150B:7, s. 984-992
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Tidskriftsartikel (refereegranskat)abstract
- Autosomal recessive hereditary spastic paraplegia (ARHSP) with thin corpus callosum (TCC) is genetically heterogenous and approximately 35% of patients carry mutations in either of the SPG11 or SPG15 genes. Disease onset is during the first three decades of life with spastic paraplegia and mental impairment. Peripheral neuropathy and amyotrophy may occur. Kjellin syndrome is characterized by central retinal degeneration in addition to ARHSP-TCC and the disease is associated with mutations in the SPG15 gene. We identified five patients in four unrelated kindreds with spastic paraplegia and mental impairment. Magnetic resonance imaging revealed TCC, atrophy elsewhere in the brain and increased T2 signal intensity in the periventricular white matter. Probands from the four kindreds were screened for mutations in the SPG11 gene. All patients were found homozygous or compound heterozygous for truncating SPG11 mutations of which four are reported for the first time. Ophthalmological investigations revealed that the four index cases have central retinal degeneration consistent with Kjellin syndrome. PET examinations with N-[11C-methyl]-L-deuterodeprenyl (DED) and fluor-18 2-fluorodeoxyglucose (FDG) were performed in two patients with Kjellin syndrome. We observed a reduced glucose uptake in the thalami, anterior cingulum, and sensorimotor cortex indicating neuronal loss, and an increased DED binding in the thalami and pons which suggests astrogliosis. From our results we extend the SPG11 associated phenotype to comprise also Kjellin syndrome, previously found to be associated with mutations in the SPG15 gene. We anticipate that degeneration of the central retina is a common and previously unrecognized feature in SPG11 related disease.
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| 7. |
- Andersson Grönlund, Marita, 1959-, et al.
(författare)
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Ophthalmological findings in children and young adults with genetically verified mitochondrial disease
- 2010
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Ingår i: British Journal of Ophthalmology. - : BMJ Publishing Group Ltd. - 0007-1161 .- 1468-2079. ; 94:1, s. 121-127
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To describe ophthalmological phenotypes in patients with mitochondrial disease and known genotypes.METHODS: A retrospective study was performed on 59 patients (29 male, 30 female) with a mean age of 11.8 years who had mitochondrial disease with known DNA mutations. Fifty-seven of the 59 subjects underwent a detailed ophthalmological examination including visual acuity (VA), eye motility, refraction, slit-lamp examination, ophthalmoscopy and, in almost one-half of the cases, a full-field electroretinogram (ERG).RESULTS: Forty-six (81%) of the patients had one or more ophthalmological findings such as ptosis (n = 16), reduced eye motility (n = 22) including severe external ophthalmoplegia (n = 9), strabismus (n = 4), nystagmus (n = 9), low VA (n = 21), refractive errors (n = 26), photophobia (n = 4), and partial or total optic atrophy (n = 25). Pigmentation in the macula and/or periphery was noted in 16 patients. In 10/27 investigated individuals with full field ERG, retinal dystrophy was recorded in six different genotypes representing Kearns-Sayre syndrome (n = 5), Leigh syndrome (n = 1), Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) (n = 1), Myoclonus epilepsy with red ragged fibres (MERRF) (n = 1), Leber hereditary optic neuropathy (n = 1) and mitochondrial myopathy (n = 1).CONCLUSION: The results show that a majority of patients with mitochondrial disorders have ophthalmological abnormalities. We recommend that an ophthalmological examination, including ERG, be performed on all children and adolescents who are suspected of having a mitochondrial disease.
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