-
51
المؤلفون: Andrea Superti-Furga, Susanne Schweitzer-Krantz, Heike Olbrich, Udo F. H. Engelke, Verena Mohr, Ron A. Wevers, Manfred Fliegauf, Ralf Moebus, Heymut Omran, Andreas Kispert, Judit Horvath, Niki T. Loges, Jörn Oliver Sass, Polly Weiler
المصدر: American Journal of Human Genetics, 78, 401-9
American Journal of Human Genetics, 78, 3, pp. 401-9مصطلحات موضوعية: medicine.medical_specialty, Energy and redox metabolism [NCMLS 4], Molecular Sequence Data, Neuroinformatics [DCN 3], Biology, medicine.disease_cause, Amidohydrolases, chemistry.chemical_compound, Mice, Valine, Internal medicine, Perception and Action [DCN 1], medicine, Genetics, Missense mutation, Animals, Humans, Genetics(clinical), Amino Acid Sequence, Amino Acids, Child, Amino Acid Metabolism, Inborn Errors, Genetics (clinical), Conserved Sequence, Aminoacylase, Mutation, Methionine, Biotinidase deficiency, Acetylation, Articles, Glycostation disorders [IGMD 4], medicine.disease, Blotting, Northern, Neuromuscular development and genetic disorders [UMCN 3.1], Rats, Endocrinology, Genetic defects of metabolism [UMCN 5.1], chemistry, Genes, Inborn error of metabolism, ACY1, Sequence Alignment
الوصف: Contains fulltext : 50017.pdf (Publisher’s version ) (Closed access) N-terminal acetylation of proteins is a widespread and highly conserved process. Aminoacylase 1 (ACY1; EC 3.5.14) is the most abundant of the aminoacylases, a class of enzymes involved in hydrolysis of N-acetylated proteins. Here, we present four children with genetic deficiency of ACY1. They were identified through organic acid analyses using gas chromatography-mass spectrometry, revealing increased urinary excretion of several N-acetylated amino acids, including the derivatives of methionine, glutamic acid, alanine, leucine, glycine, valine, and isoleucine. Nuclear magnetic resonance spectroscopy analysis of urine samples detected a distinct pattern of N-acetylated metabolites, consistent with ACY1 dysfunction. Functional analyses of patients' lymphoblasts demonstrated ACY1 deficiency. Mutation analysis uncovered recessive loss-of-function or missense ACY1 mutations in all four individuals affected. We conclude that ACY1 mutations in these children led to functional ACY1 deficiency and excretion of N-acetylated amino acids. Questions remain, however, as to the clinical significance of ACY1 deficiency. The ACY1-deficient individuals were ascertained through urine metabolic screening because of unspecific psychomotor delay (one subject), psychomotor delay with atrophy of the vermis and syringomyelia (one subject), marked muscular hypotonia (one subject), and follow-up for early treated biotinidase deficiency and normal clinical findings (one subject). Because ACY1 is evolutionarily conserved in fish, frog, mouse, and human and is expressed in the central nervous system (CNS) in human, a role in CNS function or development is conceivable but has yet to be demonstrated. Thus, at this point, we cannot state whether ACY1 deficiency has pathogenic significance with pleiotropic clinical expression or is simply a biochemical variant. Awareness of this new genetic entity may help both in delineating its clinical significance and in avoiding erroneous diagnoses.
وصف الملف: application/pdf
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::346fc350282ec1c3ff87ca617dfdc28aTest
-
52
المؤلفون: Michèl A.A.P. Willemsen, Ron A. Wevers, Eva Morava, Suzan Wopereis, H.J. ter Laak, Dirk Lefeber, Johannes R.M. Cruysberg
المصدر: European Journal of Ophthalmology, 16, 190-4
European Journal of Ophthalmology, 16, 1, pp. 190-4مصطلحات موضوعية: medicine.medical_specialty, Glycosylation, Energy and redox metabolism [NCMLS 4], Neuroinformatics [DCN 3], Cutis Laxa, Genomic disorders and inherited multi-system disorders [IGMD 3], 03 medical and health sciences, Consanguinity, 0302 clinical medicine, Muscular Diseases, Polysaccharides, Internal medicine, Perception and Action [DCN 1], medicine, Dystroglycan, Myopia, Neurosensory disorders [UMCN 3.3], Humans, Abnormalities, Multiple, Myopathy, Cerebral Cortex, Muscle biopsy, medicine.diagnostic_test, biology, Pachygyria, Muscle weakness, Infant, General Medicine, Syndrome, Glycostation disorders [IGMD 4], medicine.disease, Congenital myopathy, Magnetic Resonance Imaging, carbohydrates (lipids), Ophthalmology, Mitochondrial medicine [IGMD 8], Endocrinology, Genetic defects of metabolism [UMCN 5.1], Growth and differentiation [NCMLS 3], Neuromuscular Development and genetic Disorders [UMCN 3.1], Mutation, 030221 ophthalmology & optometry, biology.protein, Congenital muscular dystrophy, Female, medicine.symptom, 030217 neurology & neurosurgery, Cutis laxa, Carbohydrate Metabolism, Inborn Errors
الوصف: Purpose Several types of inborn errors of the O-glycan biosynthesis are known, leading to clinically very distinct phenotypes. Children with O-mannosyl glycan biosynthesis defects commonly present as a severe form of congenital muscular dystrophy with decreased alpha-dystroglycan staining, congenital eye anomalies, and brain migration defects. Alpha-dystroglycan is an O-mannosylated glycoprotein with additional mucin type O-glycans. Methods Based on overlapping clinical features with O-mannosyl glycan defects, especially with muscle-eye-brain disease, the authors performed a muscle biopsy in a child with severe congenital hypotonia, high myopia, partial pachygyria, mental retardation, cutis laxa, and an inborn error affecting the biosynthesis of both mucin type O-glycans and N-linked glycans. Results The histology showed no signs of muscle dystrophy, but a mild myopathy with slight increase in the muscle fiber diameter variability and type I fiber predominance. No significant decrease in the alpha-dystroglycan staining was detected; therefore, in spite of the phenotypic similarities the authors could not confirm the role of abnormal dystroglycan in the etiology of the muscle weakness and the developmental anomalies. Conclusions High myopia, muscle weakness, and cortical neuronal migration abnormalities are common in disorders of O-mannosylation and also observed in the authors’ patient. However, compared to the severe generalized defect observed in mannosyl glycan defects, in this child the cerebral white matter and cerebellum were spared, and no muscle dystrophy could be confirmed. This is the first description of high myopia in cutis laxa syndrome in combination with congenital disorders of glycosylation.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3c9263549463105d052c0262778399aaTest
https://hdl.handle.net/2066/49372Test -
53
المؤلفون: Eva Morava, Rodenburg, R., Hol, F., Linda De Meirleir, Sara Seneca, Busch, R., Den Heuvel, L., Jan Smeitink
المساهمون: Department of Embryology and Genetics, Pediatrics, Vrije Universiteit Brussel
المصدر: American Journal of Medical Genetics. Part A, 140, 7, pp. 752-6
Vrije Universiteit Brussel
American Journal of Medical Genetics. Part A, 140, 752-6مصطلحات موضوعية: Genomic disorders and inherited multi-system disorders [IGMD 3], Mitochondrial medicine [IGMD 8], Energy and redox metabolism [NCMLS 4], Genetic defects of metabolism [UMCN 5.1], Translational research [ONCOL 3], Glycostation disorders [IGMD 4], Brooks-Wisniewski-Brown syndrome, Cellular energy metabolism [UMCN 5.3]
الوصف: Contains fulltext : 50522.pdf (Publisher’s version ) (Closed access) Brooks, Wisniewski, and Brown described a familial presentation of severe developmental retardation, speech delay, static encephalopathy with atrophic hydrocephalus, microcephaly, progressive spastic diplegia, a characteristic facial appearance, optic atrophy, and growth retardation associated with hypoplastic corpus callosum in one of the patients. The authors postulated a distinct X-linked mental retardation syndrome. Later on a similar phenotype was observed in three male siblings with an early lethal outcome. Here we describe three patients with several overlapping features and a progressive neurological picture presenting with a significantly compromised mitochondrial oxidative phosphorylation measured in a fresh muscle biopsy. Neurological deterioration is a commonly observed feature in mitochondrial disorders. Based on the unique combination of the clinical symptoms, we suggest that our patients have the Brooks-Wisniewski-Brown syndrome.
وصف الملف: application/pdf
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=dedup_wf_001::bd45ce198a5cda6750f8f2d3d5787219Test
https://hdl.handle.net/2066/50522Test -
54
المؤلفون: Ronald J.A. Wanders, Berry Kremer, Ference J. Loupatty, Udo F. H. Engelke, Marinette van der Graaf, Erik van den Bergh, Eva Morava, Leo A. J. Kluijtmans, Sandra Loss, Detlef Moskau, Ron A. Wevers
المصدر: NMR in Biomedicine, 19, 2, pp. 271-8
NMR in Biomedicine, 19, 271-8مصطلحات موضوعية: medicine.medical_specialty, Magnetic Resonance Spectroscopy, Energy and redox metabolism [NCMLS 4], Urine, Neuroinformatics [DCN 3], Meglutol, Genomic disorders and inherited multi-system disorders [IGMD 3], Glutarates, Leukoencephalopathy, White matter, Cerebrospinal fluid, Leucine, In vivo, Internal medicine, Perception and Action [DCN 1], Valerates, medicine, Humans, Radiology, Nuclear Medicine and imaging, Amino Acid Metabolism, Inborn Errors, Spectroscopy, Chemistry, Brain, Nuclear magnetic resonance spectroscopy, Glycostation disorders [IGMD 4], Middle Aged, 3-Methylglutaconic Aciduria, medicine.disease, Neuromuscular development and genetic disorders [UMCN 3.1], Mitochondrial medicine [IGMD 8], Endocrinology, medicine.anatomical_structure, Genetic defects of metabolism [UMCN 5.1], Molecular Medicine, Female, Functional Imaging [UMCN 1.1]
الوصف: Contains fulltext : 50036.pdf (Publisher’s version ) (Closed access) A diagnosis of 3-methylglutaconic aciduria type I (OMIM: 250950) based on elevated urinary excretion of 3-methylglutaconic acid (3MGA), 3-methylglutaric acid (3MG) and 3-hydroxyisovaleric acid (3HIVA) was made in a 61-year-old female patient presenting with leukoencephalopathy slowly progressing over more than 30 years. The diagnosis was confirmed at the enzymatic and molecular level. In vivo brain MR spectroscopic imaging (MRSI) was performed at 3.0 T, and one-dimensional and two-dimensional in vitro NMR spectroscopy of body fluids of the patient was performed at 11.7 T. Additionally, we measured 1D (1)H-NMR spectra of urine of seven patients with a total of four different inborn errors of leucine metabolism. Increased concentrations of 3HIVA, 3MGA (cis and trans) and 3MG were observed in the NMR spectra of the patient's urine. In the cerebrospinal fluid, the 3HIVA concentration was 10 times higher than in the plasma of the patient and only the cis isomer of 3MGA was observed. In vivo brain MRSI showed an abnormal resonance at 1.28 ppm that may be caused by 3HIVA. Comparison of (1)H-NMR spectra of urine samples from all eight patients studied, representing five different inborn errors of leucine metabolism, showed that each disease has typical NMR characteristics. Our leukoencephalopathy patient suffers from a late-onset form of 3-methylglutaconic aciduria type I. In the literature, only very few adult patients with this conditions have been described, and 3HIVA accumulation in white matter in the brain has not been presented before in these patients. Our data demonstrate that (1)H-NMR spectroscopy of urine can easily discriminate between the known inborn errors of leucine metabolism and provide the correct diagnosis.
وصف الملف: application/pdf
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e492c54a7c2c29b3b56ecc75caa7afa5Test
https://doi.org/10.1002/nbm.1018Test -
55
المؤلفون: Burlina, Ap, Schmitt, B, Engelke, U, Wevers, Ra, Burlina, A, Boltshauser, E
المصدر: Advances in Experimental Medicine and Biology, 576, 283-7
Advances in Experimental Medicine and Biology, 576, pp. 283-7مصطلحات موضوعية: Energy and redox metabolism [NCMLS 4], Genetic defects of metabolism [UMCN 5.1], Perception and Action [DCN 1], Neuroinformatics [DCN 3], Glycostation disorders [IGMD 4], Neuromuscular development and genetic disorders [UMCN 3.1]
الوصف: Contains fulltext : 51389.pdf (Publisher’s version ) (Closed access)
وصف الملف: application/pdf
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=dedup_wf_001::b12d99abb0b9b216a735a90dd020c203Test
https://hdl.handle.net/2066/51389Test -
56
المؤلفون: Lambert P. van den Heuvel, Murtada H Farhoud, Baziel G.M. van Engelen, Jan A.M. Smeitink, Hans J. C. T. Wessels, Ron A. Wevers
المصدر: Journal of Proteome Research, 4, 2364-8
Journal of Proteome Research, 4, 6, pp. 2364-8مصطلحات موضوعية: Proteomics, Proteome, Energy and redox metabolism [NCMLS 4], Resolution (mass spectrometry), Computer science, Sample (material), STRIPS, Neuroinformatics [DCN 3], Biochemistry, law.invention, Genomic disorders and inherited multi-system disorders [IGMD 3], Translational research [ONCOL 3], law, Perception and Action [DCN 1], Humans, Narrow range, Electrophoresis, Gel, Two-Dimensional, Isoelectric Point, Throughput (business), Human Movement & Fatigue [NCEBP 10], Chromatography, Isoelectric focusing, Myocardium, Temperature, Proteins, General Chemistry, Hydrogen-Ion Concentration, Glycostation disorders [IGMD 4], Neuromuscular development and genetic disorders [UMCN 3.1], Mitochondria, Mitochondrial medicine [IGMD 8], Proof of concept, Indicators and Reagents, Isoelectric Focusing, Cellular energy metabolism [UMCN 5.3], Functional Neurogenomics [DCN 2], Algorithm
الوصف: Contains fulltext : 48163.pdf (Publisher’s version ) (Closed access) In 2D-based comparative proteomics of scarce samples, such as limited patient material, established methods for prefractionation and subsequent use of different narrow range IPG strips to increase overall resolution are difficult to apply. Also, a high number of samples, a prerequisite for drawing meaningful conclusions when pathological and control samples are considered, will increase the associated amount of work almost exponentially. Here, we introduce a novel, effective, and economic method designed to obtain maximum 2D resolution while maintaining the high throughput necessary to perform large-scale comparative proteomics studies. The method is based on connecting different IPG strips serially head-to-tail so that a complete line of different IPG strips with sequential pH regions can be focused in the same experiment. We show that when 3 IPG strips (covering together the pH range of 3-11) are connected head-to-tail an optimal resolution is achieved along the whole pH range. Sample consumption, time required, and associated costs are reduced by almost 70%, and the workload is reduced significantly.
وصف الملف: application/pdf
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4857eb3a84fa69eaac48efa76da57502Test
https://doi.org/10.1021/pr050231aTest -
57
المؤلفون: H. Zweers van Essen, Saskia B. Wortmann, Eva Morava, R. Liebrand van Sambeek, O. P. van Diggelen, Ron A. Wevers
المساهمون: Clinical Genetics
المصدر: Journal of Inherited Metabolic Disease, 28, 5, pp. 703-6
Journal of Inherited Metabolic Disease, 28, 703-6
Journal of Inherited Metabolic Disease, 28(5), 703-706. Springer Netherlandsمصطلحات موضوعية: Male, Heterozygote, medicine.medical_specialty, Erythrocytes, Energy and redox metabolism [NCMLS 4], Phosphorylase Kinase, Butanols, Urinary system, Oligosaccharides, 1-Propanol, Urine, Neuroinformatics [DCN 3], Biology, Biochemistry, High cholesterol, Genomic disorders and inherited multi-system disorders [IGMD 3], Excretion, Hemoglobins, chemistry.chemical_compound, Glucosides, Internal medicine, Perception and Action [DCN 1], Genetics, medicine, Humans, Glycogen storage disease, Phosphorylase kinase, Genetics (clinical), Family Health, Triglyceride, Glycostation disorders [IGMD 4], Glycogen Storage Disease, medicine.disease, Neuromuscular development and genetic disorders [UMCN 3.1], Quality of Care [EBP 4], Mitochondrial medicine [IGMD 8], Cholesterol, Endocrinology, Genetic defects of metabolism [UMCN 5.1], chemistry, Female, lipids (amino acids, peptides, and proteins), Chromatography, Thin Layer, Growth delay, Functional Neurogenomics [DCN 2], Blood Chemical Analysis
الوصف: Contains fulltext : 47742.pdf (Publisher’s version ) (Closed access) Patients with glycogen storage disease type IXa present with infantile hepatomegaly and a specific growth pattern, and variable biochemical alterations in blood. We studied the clinical and biochemical characteristics including the urinary oligosaccharide excretion of seven unrelated children. The urinary tetraglucoside excretion was increased in four children, three of whom had persistently high cholesterol and triglyceride concentrations. We propose screening for urine tetraglucoside excretion and the measurement of serum cholesterol in patients with growth delay and/or hepatomegaly to assess a possible glycogenosis.
وصف الملف: application/pdf
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4d847a4f35d29dae3f9f1d5f3de7fb14Test
https://doi.org/10.1007/s10545-005-0095-9Test -
58
المؤلفون: Jaak Jaeken, Jaap A. Bakker, Richard Steet, H. J. Sijstermans, L. J. M. Spaapen, S. B. van der Meer, Ron A. Wevers
المصدر: Journal of Inherited Metabolic Disease, 28, 5, pp. 707-14
Journal of Inherited Metabolic Disease, 28, 707-14مصطلحات موضوعية: Male, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, Glycosylation, Energy and redox metabolism [NCMLS 4], Apolipoprotein B, Golgi Apparatus, Neuroinformatics [DCN 3], Biology, chemistry.chemical_compound, symbols.namesake, Congenital Disorders of Glycosylation, N-linked glycosylation, Internal medicine, Leukocytes, Perception and Action [DCN 1], Genetics, medicine, Humans, Protein Isoforms, Apolipoproteins C, Genetics (clinical), Glycoproteins, Family Health, chemistry.chemical_classification, Apolipoprotein C-III, Isoelectric focusing, Siblings, Conserved oligomeric Golgi complex, Transferrin, Fibroblasts, Glycostation disorders [IGMD 4], Golgi apparatus, N-Acetylneuraminic Acid, Neuromuscular development and genetic disorders [UMCN 3.1], Sialic acid, Endocrinology, Liver, Genetic defects of metabolism [UMCN 5.1], chemistry, biology.protein, symbols, Female, Isoelectric Focusing, Lysosomes, Glycoprotein, Functional Neurogenomics [DCN 2], Carbohydrate Metabolism, Inborn Errors
الوصف: Contains fulltext : 48723.pdf (Publisher’s version ) (Closed access) Congenital disorders of glycosylation (CDG) represent a group of inherited multiorgan diseases caused by defects in the biosynthesis of glycoproteins. We report on two dysmorphic siblings with severe liver disease who died at the age of a few weeks. Increased activities of lysosomal enzymes in plasma were found, though total sialic acid in plasma was strongly decreased. Isoelectric focusing of serum sialotransferrins showed a type 2-like CDG pattern. Some of the known CDG subtypes were excluded. O-Glycosylation was investigated by isoelectric focusing of apolipoprotein C-III, which showed increased fractions of hyposialylated isoforms. In a consecutive study a defect in the conserved oligomeric Golgi complex was established at the level of subunit COG-7, leading to disruption of multiple glycosylation functions of the Golgi. This report on patients with a new variant of CDG, due to a multiple Golgi defect, emphasizes in addition to sialotransferrins the importance of analysis of a serum O-linked glycoprotein, e.g. apolipoprotein C-III, in unclassified CDG-X cases.
وصف الملف: application/pdf
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::96af222bfb63c8e8448a8c05e0262e79Test
https://doi.org/10.1007/s10545-005-0015-zTest -
59
المؤلفون: Bryan Winchester, Suzan Wopereis, Ron A. Wevers, Stephanie Grunewald, Paul Coucke, Peter E. Clayton, Karin Huijben, Eva Morava, Philippa B. Mills
المصدر: Biochimica et Biophysica Acta. Molecular Basis of Disease, 1741, 1-2, pp. 156-64
Biochimica et Biophysica Acta. Molecular Basis of Disease, 1741, 156-64مصطلحات موضوعية: Glycosylation, N-glycosylation, Neuroinformatics [DCN 3], Cutis Laxa, Mass Spectrometry, Extracellular matrix, Consanguinity, chemistry.chemical_compound, 0302 clinical medicine, N-linked glycosylation, Perception and Action [DCN 1], O-glycosylation, Extracellular Matrix Proteins, 0303 health sciences, Transferrin, Pedigree, 3. Good health, Mitochondrial medicine [IGMD 8], Glycan biosynthesis defect, Biochemistry, Child, Preschool, FBLN5, Molecular Medicine, Carbohydrate Metabolism, Inborn Errors, Energy and redox metabolism [NCMLS 4], Genes, Recessive, Genomic disorders and inherited multi-system disorders [IGMD 3], Abnormal glycosylation, 03 medical and health sciences, Polysaccharides, medicine, Humans, Apolipoproteins C, Molecular Biology, 030304 developmental biology, Congenital disorder of glycosylation, Infant, Glycostation disorders [IGMD 4], medicine.disease, Molecular biology, Neuromuscular development and genetic disorders [UMCN 3.1], Sialic acid, carbohydrates (lipids), Genetic defects of metabolism [UMCN 5.1], chemistry, Isoelectric Focusing, Nervous System Diseases, 030217 neurology & neurosurgery, Cutis laxa
الوصف: Contains fulltext : 48953.pdf (Publisher’s version ) (Closed access) Based on our preliminary observation of abnormal glycosylation in a cutis laxa patient, nine cutis laxa patients were analyzed for congenital defects of glycosylation (CDG). Isoelectric focusing of plasma transferrin and apolipoproteinC-III showed that three out of nine patients had a defect in the biosynthesis of N-glycans and core 1 mucin type O-glycans, respectively. Mass spectrometric N-glycan analyses revealed a relative increase of glycans lacking sialic acid and glycans lacking sialic acid and galactose residues. Mutation analysis of the fibulin-5 gene (FBLN5), which has been reported in cases of autosomal recessive cutis laxa, revealed no mutations in the patients' DNA. Evidence is presented that extracellular matrix (ECM) proteins of skin are likely to be highly glycosylated with N- and/or mucin type O-glycans by using algorithms for predicting glycosylation. The conclusions in this study were that the clinical phenotype of autosomal recessive cutis laxa seen in three patients is not caused by mutations in the FBLN5 gene. Our findings define a novel form of CDG with cutis laxa and neurological involvement due to a defect in the sialylation and/or galactosylation of N- and O-glycans. Improper glycosylation of ECM proteins of skin may form the pathophysiological basis for the cutis laxa phenotype.
وصف الملف: application/pdf
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8262e6f8abfb00be06c4f93bc93a1181Test
https://doi.org/10.1016/j.bbadis.2004.11.009Test -
60
المؤلفون: H.Y. Kroes, Eva Morava, L.P.W.J. van den Heuvel, A. Dinopoulos, J.H.L.M. van Bokhoven, Jan A.M. Smeitink, Richard J. Rodenburg
المصدر: Neuropediatrics, 36, 214-7
Neuropediatrics, 36, 3, pp. 214-7مصطلحات موضوعية: Pyruvate decarboxylation, medicine.medical_specialty, Pathology, Mitochondrial Diseases, Ataxia, Energy and redox metabolism [NCMLS 4], Genetics and epigenetic pathways of disease [NCMLS 6], Eye Diseases, Mitochondrial disease, Joubert syndrome, Marfan Syndrome, Genomic disorders and inherited multi-system disorders [IGMD 3], Translational research [ONCOL 3], Cerebellum, Internal medicine, medicine, Neurosensory disorders [UMCN 3.3], Humans, Abnormalities, Multiple, Cerebellar hypoplasia, Psychomotor retardation, business.industry, Infant, Newborn, Facies, Syndrome, General Medicine, Glycostation disorders [IGMD 4], medicine.disease, Hypotonia, eye diseases, Pyruvate dehydrogenase deficiency, Mitochondrial medicine [IGMD 8], Endocrinology, Pediatrics, Perinatology and Child Health, Muscle Hypotonia, Female, Neurology (clinical), medicine.symptom, Cellular energy metabolism [UMCN 5.3], business, Functional Neurogenomics [DCN 2], Follow-Up Studies
الوصف: Contains fulltext : 48821.pdf (Publisher’s version ) (Closed access) Joubert syndrome is a genetically heterogeneous disorder. The diagnostic criteria include episodic hyperventilation, abnormal eye movements, psychomotor retardation, hypotonia, ataxia, and the characteristic neuro-imaging findings (molar-tooth sign). Many of these clinical features have been observed in new-borns with mitochondrial disorders as well. Congenital brain malformations, including cerebellar hypoplasia, have been described in pyruvate dehydrogenase deficiency. Malformations of the vermis and the cerebellar peduncles, with the lack of axonal decussations, however, are characteristic for Joubert syndrome but unique in patients with mitochondrial disorders. Here, we describe a child with Joubert syndrome presenting with primary lactic acidemia, decreased pyruvate oxidation rates, decreased ATP production, and a mildly decreased pyruvate dehydrogenase complex activity measured in a fresh muscle biopsy. Sequence analysis of the PDHc E1 alpha gene and the PDHX genes revealed no mutations. The patient received continuous feeding through a feeding tube for two years and showed a significant clinical improvement with a complete resolution of the chronic lactic acidemia. A second muscle biopsy revealed significantly decreased pyruvate oxidation rates and ATP production, but a normal pyruvate dehydrogenase complex activity. We suggest that the described mitochondrial dysfunction in our patient is secondary to an underlying mutation leading to Joubert syndrome.
وصف الملف: application/pdf
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a1eb18ecc476d8d18fad572bab71820fTest
https://hdl.handle.net/2066/48821Test
