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Article
Open AccessDifferenzierte Herangehensweise und Testung seltener genetischer Erkrankungen im Kindes- und Jugendalter
Genetische Diagnostik hat mittlerweile praktisch alle Bereiche der Kinderheilkunde erreicht. Immer häufiger stellt die Humangenetik ein wichtiges Instrument ergänzend zur klinischen Diagnostik dar und nimmt zu...
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Article
Open AccessMesenchymal stem cells improve redox homeostasis and mitochondrial respiration in fibroblast cell lines with pathogenic MT-ND3 and MT-ND6 variants
The most frequent biochemical defect of inherited mitochondrial disease is isolated complex I deficiency. There is no cure for this disorder, and treatment is mainly supportive. In this study, we investigated ...
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Article
Open AccessNeuroligin-mediated neurodevelopmental defects are induced by mitochondrial dysfunction and prevented by lutein in C. elegans
Complex-I-deficiency represents the most frequent pathogenetic cause of human mitochondriopathies. Therapeutic options for these neurodevelopmental life-threating disorders do not exist, partly due to the scar...
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Article
Open AccessClinical implementation of RNA sequencing for Mendelian disease diagnostics
Lack of functional evidence hampers variant interpretation, leaving a large proportion of individuals with a suspected Mendelian disorder without genetic diagnosis after whole genome or whole exome sequencing ...
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Article
Open AccessNBAS Variants Are Associated with Quantitative and Qualitative NK and B Cell Deficiency
Biallelic pathogenic NBAS variants manifest as a multisystem disorder with heterogeneous clinical phenotypes such as recurrent acute liver failure, growth retardation, and susceptibility to infections. This study...
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Article
Open AccessThe long non-coding RNA HOTAIRM1 promotes tumor aggressiveness and radiotherapy resistance in glioblastoma
Glioblastoma is the most common malignant primary brain tumor. To date, clinically relevant biomarkers are restricted to isocitrate dehydrogenase (IDH) gene 1 or 2 mutations and O6-methylguanine DNA methyltran...
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Article
Open AccessCorrection to: The antioxidant Trolox restores mitochondrial membrane potential and Ca2+-stimulated ATP production in human complex I deficiency
A Correction to this paper has been published: https://doi.org/10.1007/s00109-021-02057-3
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Article
Open AccessBiallelic VARS variants cause developmental encephalopathy with microcephaly that is recapitulated in vars knockout zebrafish
Aminoacyl tRNA synthetases (ARSs) link specific amino acids with their cognate transfer RNAs in a critical early step of protein translation. Mutations in ARSs have emerged as a cause of recessive, often compl...
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Mitochondrial Symptomatic Treatments
Based on improvements in diagnostic strategies, the group of genetically defined mitochondrial diseases is rapidly growing. This advances our understanding of the underlying pathophysiology and is important fo...
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Article
Severe ichthyosis in MPDU1-CDG
Congenital disorders of glycosylation (CDG) have a broad spectrum of clinical manifestations. They can affect multiple organ systems, including skin and subcutaneous tissue. We report on an infant with severe ...
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Article
Open AccessChallenges of palliative care in children with inborn metabolic diseases
Our objective was to evaluate children with metabolic diseases in paediatric palliative home care (PPC) and the process of decision-making. This study was conducted as single-centre retrospective cohort study ...
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Article
Open AccessA scoring system predicting the clinical course of CLPB defect based on the foetal and neonatal presentation of 31 patients
Recently, CLPB deficiency has been shown to cause a genetic syndrome with cataracts, neutropenia, and 3-methylglutaconic aciduria. Surprisingly, the neurological presentation ranges from completely unaffected ...
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Article
Open AccessModulation of oxidative phosphorylation and redox homeostasis in mitochondrial NDUFS4 deficiency via mesenchymal stem cells
Disorders of the oxidative phosphorylation (OXPHOS) system represent a large group among the inborn errors of metabolism. The most frequently observed biochemical defect is isolated deficiency of mitochondrial...
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Article
Open AccessGenetic diagnosis of Mendelian disorders via RNA sequencing
Across a variety of Mendelian disorders, ∼50–75% of patients do not receive a genetic diagnosis by exome sequencing indicating disease-causing variants in non-coding regions. Although genome sequencing in prin...
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Article
Neonatal encephalocardiomyopathy caused by mutations in VARS2
VARS2 encodes a mitochondrial aminoacyl-tRNA-synthetase. Mutations in VARS2 have recently been identified as a cause of mitochondrial encephalomyopathy in three individuals. However, clin...
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Article
The many faces of paediatric mitochondrial disease on neuroimaging
The knowledge about the genetic spectrum underlying paediatric mitochondrial diseases is rapidly growing. As a consequence, the range of neuroimaging findings associated with mitochondrial diseases became extr...
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Article
EARS2 mutations cause fatal neonatal lactic acidosis, recurrent hypoglycemia and agenesis of corpus callosum
Mitochondrial aminoacyl tRNA synthetases are essential for organelle protein synthesis. Genetic defects affecting the function of these enzymes may cause pediatric mitochondrial disease. Here, we report on a c...
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Article
Recurrent acute liver failure due to NBAS deficiency: phenotypic spectrum, disease mechanisms, and therapeutic concepts
Acute liver failure (ALF) in infancy and childhood is a life-threatening emergency and in about 50 % the etiology remains unknown. Recently biallelic mutations in NBAS were identified as a new molecular cause of ...
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Article
MRPL44 mutations cause a slowly progressive multisystem disease with childhood-onset hypertrophic cardiomyopathy
Defects in mitochondrial translation may lead to combined respiratory chain deficiency and typically cause childhood-onset multisystem disease. Only recently, a homozygous missense mutation (c.467T > G, p.Leu1...
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Article
Clinical, morphological, biochemical, imaging and outcome parameters in 21 individuals with mitochondrial maintenance defect related to FBXL4 mutations
FBXL4 deficiency is a recently described disorder of mitochondrial maintenance associated with a loss of mitochondrial DNA in cells. To date, the genetic diagnosis of FBXL4 deficiency has...
