| 书目名称 | JIMD Reports, Volume 27 | | 编辑 | Eva Morava,Matthias Baumgartner,Verena Peters | | 视频video | http://file.papertrans.cn/501/500065/500065.mp4 | | 概述 | Unique collection of case and research reports on rare metabolic disorders.Contains unusual or previously unrecorded features relevant to metabolic disorders.All contributions rigorously peer-reviewed | | 丛书名称 | JIMD Reports | | 图书封面 |  | | 描述 | JIMD Reports publishes case and short research reports in the area of inherited metabolic disorders. Case reports highlight some unusual or previously unrecorded feature relevant to the disorder, or serve as an important reminder of clinical or biochemical features of a Mendelian disorder. | | 出版日期 | Book 2016 | | 关键词 | inherited metabolic diseases; pediatrics; medical genetics; Mendelian disorder; endocrinology; metabolic | | 版次 | 1 | | doi | https://doi.org/10.1007/978-3-662-50409-3 | | isbn_softcover | 978-3-662-50408-6 | | isbn_ebook | 978-3-662-50409-3Series ISSN 2192-8304 Series E-ISSN 2192-8312 | | issn_series | 2192-8304 | | copyright | SSIEM and Springer-Verlag Berlin Heidelberg 2016 |
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Front Matter |
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Abstract
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,Detailed Biochemical and Bioenergetic Characterization of ,-Related Encephalomyopathic Mitochondria |
Ghadi Antoun,Skye McBride,Jason R. Vanstone,Turaya Naas,Jean Michaud,Stephanie Redpath,Hugh J. McMil |
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Abstract
Mutations of ., which encodes an orphan mitochondrial F-box protein, are a recently identified cause of encephalomyopathic mtDNA depletion. Here, we describe the detailed clinical and biochemical phenotype of a neonate presenting with hyperlactatemia, leukoencephalopathy, arrhythmias, pulmonary hypertension, dysmorphic features, and lymphopenia. Next-generation sequencing in the proband identified a homozygous frameshift, c.1641_1642delTG, in ., with a surrounding block of SNP marker homozygosity identified by microarray. Muscle biopsy showed a paucity of mitochondria with ultrastructural abnormalities, mitochondrial DNA depletion, and profound deficiency of all respiratory chain complexes. Cell-based mitochondrial phenotyping in fibroblasts showed mitochondrial fragmentation, decreased basal and maximal respiration, absence of ATP-linked respiratory and leak capacity, impaired survival under obligate aerobic respiration, and reduced mitochondrial inner membrane potential, with relative sparing of mitochondrial mass. Cultured fibroblasts from the patient exhibited a more oxidized glutathione ratio, consistent with altered cellular redox poise. High-resolution respirometry of permea
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,Recurrent Ventricular Tachycardia in Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency, |
P. Bala,S. Ferdinandusse,S. E. Olpin,P. Chetcuti,A. A. M. Morris |
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Abstract
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,Application of an Image Cytometry Protocol for Cellular and Mitochondrial Phenotyping on Fibroblast |
Paula Fernandez-Guerra,M. Lund,T. J. Corydon,N. Cornelius,N. Gregersen,J. Palmfeldt,Peter Bross |
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Abstract
Cellular phenotyping of human dermal fibroblasts (HDFs) from patients with inherited diseases provides invaluable information for diagnosis, disease aetiology, prognosis and assessing of treatment options. Here we present a cell phenotyping protocol using image cytometry that combines measurements of crucial cellular and mitochondrial parameters: (1) cell number and viability, (2) thiol redox status (TRS), (3) mitochondrial membrane potential (MMP) and (4) mitochondrial superoxide levels (MSLs). With our protocol, cell viability, TRS and MMP can be measured in one small cell sample and MSL on a parallel one. We analysed HDFs from healthy individuals after treatment with various concentrations of hydrogen peroxide (H.O.) for different intervals, to mimic the physiological effects of oxidative stress. Our results show that cell number, viability, TRS and MMP decreased, while MSL increased both in a time- and concentration-dependent manner. To assess the use of our protocol for analysis of HDFs from patients with inherited diseases, we analysed HDFs from two patients with very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency (VLCADD), one with a severe clinical phenotype and one w
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,, Deficiency: A Deafness-Dystonia Syndrome with Distinctive Metabolic Findings (Report of a New Pat |
Roeltje R. Maas,Adela Della Marina,Arjan P. M. de Brouwer,Ron A. Wevers,Richard J Rodenburg,Saskia B |
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Abstract
. encodes for a subunit of succinyl-coenzyme A synthase, the enzyme that reversibly synthesises succinyl-coenzyme A and ATP from succinate, coenzyme A and ADP in the Krebs cycle. Disruption of . function can lead to mitochondrial DNA depletion. Patients with a . mutation present with a rare but distinctive deafness-dystonia syndrome. Additionally, they exhibit elevated levels of the characteristic biochemical markers: methylmalonate, C4-dicarboxylic carnitine and lactate are increased in both plasma and urine. Thus far, eight different disease-causing . mutations, of which six missense mutations and two splice site mutations, have been described in the literature. Here, we present the first patient with an intragenic deletion in . and review the patients described in literature.
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,Diagnostic Value of Urinary Mevalonic Acid Excretion in Patients with a Clinical Suspicion of Meval |
Jerold Jeyaratnam,Nienke M. ter Haar,Monique G. M. de Sain-van der Velden,Hans R. Waterham,Mariëlle |
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Abstract
.: In patients suffering from mevalonate kinase deficiency (MKD), the reduced enzyme activity leads to an accumulation of mevalonic acid which is excreted in the urine. This study aims to evaluate the diagnostic value of urinary mevalonic acid measurement in patients with a clinical suspicion of mevalonate kinase deficiency...: In this single-center, retrospective analysis, all patients in whom both measurement of mevalonic acid and genetic testing had been performed in the preceding 17 years have been included. The presence of two pathogenic . mutations or demonstration of decreased enzyme activity was considered to be the gold standard for the diagnosis of MKD...: Sixty-one patients were included in this study. Thirteen of them harbored two . mutations; twelve of them showed elevated levels of mevalonic acid. Forty-eight patients did not harbor any . mutations, yet five of them excreted increased amounts of mevalonic acid. This corresponds to a sensitivity of 92%, a specificity of 90%, a positive predictive value of 71%, and a negative predictive value of 98%. The positive likelihood ratio is 10 and the negative likelihood ratio is 0.09...: MKD seems very unlikely in patients wit
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,Hyperprolinemia in Type 2 Glutaric Aciduria and MADD-Like Profiles, |
Clément Pontoizeau,Florence Habarou,Anaïs Brassier,Alice Veauville-Merllié,Coraline Grisel,Jean-Bapt |
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Abstract
Classical neonatal-onset glutaric aciduria type 2 (MAD deficiency) is a severe disorder of mitochondrial fatty acid oxidation associated with poor survival. Secondary dysfunction of acyl-CoA dehydrogenases may result from deficiency for riboflavin transporters, leading to severe disorders that, nevertheless, are treatable by riboflavin supplementation. In the last 10 years, we identified nine newborns with biochemical features consistent with MAD deficiency, only four of whom survived past the neonatal period. A likely iatrogenic cause of riboflavin deficiency was found in two premature newborns having parenteral nutrition, one of whom recovered upon multivitamin supplementation, whereas the other died before diagnosis. Four other patients had demonstrated mutations involving ETF or ETF-DH flavoproteins, whereas the remaining three patients presumably had secondary deficiencies of unknown mechanism. Interestingly, six newborns among the seven tested for plasma amino acids had pronounced hyperprolinemia. In one case, because the initial diagnostic workup did not include organic acids and acylcarnitine profiling, clinical presentation and hyperprolinemia suggested the diagnosis. Anal
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,IgG ,-Glycosylation Galactose Incorporation Ratios for the Monitoring of Classical Galactosaemia, |
Henning Stockmann,Karen P. Coss,M. Estela Rubio-Gozalbo,Ina Knerr,Maria Fitzgibbon,Ashwini Maratha,J |
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Abstract
Classical galactosaemia (OMIM #230400) is a rare disorder of carbohydrate metabolism caused by deficiency of the galactose-1-phosphate uridyltransferase enzyme (EC 2.7.7.12). The cause of the long-term complications, including neurological, cognitive and fertility problems in females, remains poorly understood. The relatively small number of patients with galactosaemia and the lack of validated biomarkers pose a substantial challenge for determining prognosis and monitoring disease progression and responses to new therapies. We report an improved method of automated robotic hydrophilic interaction ultra-performance liquid chromatography .-glycan analysis for the measurement of IgG .-glycan galactose incorporation ratios applied to the monitoring of adult patients with classical galactosaemia. We analysed 40 affected adult patients and 81 matched healthy controls. Significant differences were noted between the G0/G1 and G0/G2 incorporation ratios between galactosaemia patients and controls (. < 0.001 and <0.01, respectively). Our data indicate that the use of IgG .-glycosylation galactose incorporation analysis may be now applicable for monitoring patient dietary compliance, determi
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,Intracranial Pressure Monitoring Demonstrates that Cerebral Edema Is Not Correlated to Hyperammonem |
Julie Chantreuil,Géraldine Favrais,Nadine Fakhri,Marine Tardieu,Nicolas Roullet-Renoleau,Thierry Per |
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Abstract
.: Ornithine transcarbamylase deficiency (OTCD) is an inborn error of urea cycle resulting in increased plasma levels of ammonia and glutamine and cerebral edema. However, the underlying mechanism of brain cytotoxicity remains controversial. Our objective is to present an unusual acute hyperammonemic crisis suggesting a key role of brain glutamine to mediate ammonia neurotoxicity and the interest of intracerebral pressure (ICP) monitoring to maintain adequate cerebral perfusion pressure and to prevent neurological damages...: A 6-year-old boy with OTCD was admitted for an acute hyperammonemic encephalopathy following viral infection. At admission, he presented vomiting, confusion, lethargy (Glasgow scale 7/15), and bilateral papilledema, suggesting cerebral edema. Plasma ammonia level was slightly increased (194 μmol/L, rr 25–50 μmol/L), contrasting with the severity of neurological deterioration and with high levels of glutamine in plasma (1,949 μmol/L, rr 335–666 μmol/L) and the brain (10-fold increase on in vivo MR spectroscopy). The patient was placed on neuroprotective treatments and respiratory support...: With a hypercaloric protein-free diet and nitrogen scavenger drugs, pl
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,No Evidence for Association of , Heterozygosity with High-Grade Myopia or Other Diseases with Possi |
Dorota Piekutowska-Abramczuk,Beata Kocyła-Karczmarewicz,Maja Małkowska,Sylwia Łuczak,Katarzyna Iwani |
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Abstract
. mutations cause recessively inherited cytochrome . oxidase deficiency. Recently Tran-Viet et al. proposed that heterozygosity for pathogenic . variants, including the common E140K variant, causes high-grade myopia. To investigate the association of . mutations with myopia, ophthalmic examinations were performed on 35 E140K carriers, one homozygous infant, and on a mouse model of Sco2 deficiency. Additionally, a screen for other putative effects of . heterozygosity was carried out by comparing the prevalence of the common E140K variant in a population of patients with undiagnosed diseases compatible with .-related pathogenesis to that in a general population sample. High-grade myopia was not identified in any of the studied individuals. Of the carriers, 17 were emmetropic, and 18 possessed refractive errors. Additionally, no significant axial elongation indicative of high-grade myopia was found in mice carrying E129K (corresponding to E140K in humans) knock-in mutations. The prevalence of E140K carriers in the symptomatic cohort was evaluated as 1:103 (CI: 0.44–2.09) and did not differ significantly from the population prevalence (1:147, CI: 0.45–1.04)..Our study demonstrates that
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,Voluntary Exercise Prevents Oxidative Stress in the Brain of Phenylketonuria Mice, |
Priscila Nicolao Mazzola,Vibeke Bruinenberg,Karen Anjema,Danique van Vliet,Carlos Severo Dutra-Filho |
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Abstract
.: High phenylalanine levels in phenylketonuria (PKU) have been associated with brain oxidative stress and amino acid imbalance. Exercise has been shown to improve brain function in hyperphenylalaninemia and neurodegenerative diseases. This study aimed to verify the effects of exercise on coordination and balance, plasma and brain amino acid levels, and brain oxidative stress markers in PKU mice...: Twenty wild-type (WT) and 20 PAH. (PKU) C57BL/6 mice were placed in cages with (exercise, Exe) or without (sedentary, Sed) running wheels during 53 days. At day 43, a balance beam test was performed. Plasma and brain were collected for analyses of amino acid levels and the oxidative stress parameters superoxide dismutase (SOD) activity, sulfhydryl and reduced glutathione (GSH) contents, total radical-trapping antioxidant potential (TRAP), and total antioxidant reactivity (TAR)...: SedPKU showed poor coordination (. < 0.001) and balance (. < 0.001), higher plasma and brain phenylalanine (. < 0.001), and increased brain oxidative stress (. < 0.05) in comparison to SedWT. ExePKU animals ran less than ExeWT (. = 0.018). Although no improvement was seen in motor coordination and balance, exe
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,Seizures Due to a , Mutation: Treatment with Vitamin B,, |
Emma S. Reid,Hywel Williams,Polona Le Quesne Stabej,Chela James,Louise Ocaka,Chiara Bacchelli,Emma J |
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Abstract
There is increasing evidence that vitamin B., given either as pyridoxine or pyridoxal 5′-phosphate, can sometimes result in improved seizure control in idiopathic epilepsy. Whole-exome sequencing was used to identify a . mutation (c.629G>A; p.Arg210His) in . in a 7-year-old patient whose neonatal seizures showed a response to pyridoxine and who had a high plasma to CSF pyridoxal 5′-phosphate ratio, usually indicative of an inborn error of vitamin B. metabolism. This mutation has been described in three other patients with neonatal epileptic encephalopathy. A review of the literature was performed to assess the effectiveness of vitamin B. treatment in patients with a KCNQ2 channelopathy. Twenty-three patients have been reported to have been trialled with B.; in three of which B. treatment was used alone or in combination with other antiepileptic drugs to control seizures. The anticonvulsant effect of B. vitamers may be propagated by multiple mechanisms including direct antagonist action on ion channels, antioxidant action on excess reactive oxygen species generated by increased neuronal firing and replenishing the pool of pyridoxal 5′-phosphate needed for the synthesis of some inhib
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,The Frequencies of Different Inborn Errors of Metabolism in Adult Metabolic Centres: Report from th |
S. Sirrs,C. Hollak,M. Merkel,A. Sechi,E. Glamuzina,M. C. Janssen,R. Lachmann,J. Langendonk,M. Scarpe |
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Abstract
.: There are few centres which specialise in the care of adults with inborn errors of metabolism (IEM). To anticipate facilities and staffing needed at these centres, it is of interest to know the distribution of the different disorders...: A survey was distributed through the list-serve of the SSIEM Adult Metabolic Physicians group asking clinicians for number of patients with confirmed diagnoses, types of diagnoses and age at diagnosis...: Twenty-four adult centres responded to our survey with information on 6,692 patients. Of those 6,692 patients, 510 were excluded for diagnoses not within the IEM spectrum (e.g. bone dysplasias, hemochromatosis) or for age less than 16 years, leaving 6,182 patients for final analysis. The most common diseases followed by the adult centres were phenylketonuria (20.6%), mitochondrial disorders (14%) and lysosomal storage disorders (Fabry disease (8.8%), Gaucher disease (4.2%)). Amongst the disorders that can present with acute metabolic decompensation, the urea cycle disorders, specifically ornithine transcarbamylase deficiency, were most common (2.2%), followed by glycogen storage disease type I (1.5%) and maple syrup urine disease (1.1%). Patien
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,Electroclinical Features of Early-Onset Epileptic Encephalopathies in Congenital Disorders of Glyco |
Agata Fiumara,Rita Barone,Giuliana Del Campo,Pasquale Striano,Jaak Jaeken |
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Abstract
Congenital disorders of glycosylation (CDG) are a constantly growing group of genetic defects of glycoprotein and glycolipid glycan synthesis. CDGs are usually multisystem diseases, and in the majority of patients, there is an important neurological involvement comprising psychomotor disability, hypotonia, ataxia, seizures, stroke-like episodes, and peripheral neuropathy. To assess the incidence, among early-onset epileptic encephalopathies (EOEE), of patients with identified congenital disorders of glycosylation (CDG), we made a review of clinical, electrophysiological, and neuroimaging findings of 27 CDG patients focusing on seizure onset, semiology and frequency, response to antiepileptic drugs (AED), and early epileptic manifestations. Epilepsy was uncommon in PMM2-CDG (11%), while it was a main concern in other rare forms. We describe a series of patients with EOEE and genetically confirmed CDG (ALG3-CDG, ALG6-CDG, DPM2-CDG, ALG1-CDG). Epileptic seizures at onset included myoclonic and clonic fits and focal seizures. With time, patients developed recurrent and intractable seizures principally tonic–clonic seizures, infantile spasms, and myoclonic seizures. Electrophysiological
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,The Newborn Screening Paradox: Sensitivity vs. Overdiagnosis in VLCAD Deficiency, |
Eugene Diekman,Monique de Sain-van der Velden,Hans Waterham,Leo Kluijtmans,Peter Schielen,Evert Ben |
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Abstract
.: To improve the efficacy of newborn screening (NBS) for very long chain acyl-CoA dehydrogenase deficiency (VLCADD)...: Data on all dried blood spots collected by the Dutch NBS from October 2007 to 2010 (742.728) were included. Based solely on the C14:1 levels (cutoff ≥0.8 μmol/L), six newborns with VLCADD had been identified through NBS during this period. The ratio of C14:1 over C2 was calculated. DNA of all blood spots with a C14:1/C2 ratio of ≥0.020 was isolated and sequenced. Children homozygous or compound heterozygous for mutations in the . gene were traced back and invited for detailed clinical, biochemical, and genetic evaluation...: Retrospective analysis based on the C14:1/C2 ratio with a cutoff of ≥0.020 identified an additional five children with known . mutations and low enzymatic activity. All were still asymptomatic at the time of diagnosis (age 2–5 years). Increasing the cutoff to ≥0.023 resulted in a sensitivity of 93% and a positive predictive value of 37%. The sensitivity of the previously used screening approach (C14:1 ≥0.8) was 50%...: This study shows that the ratio C14:1/C2 is a more sensitive marker than C14:1 for identifying VLCADD patients in NBS. Howeve
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,Further Delineation of the ALG9-CDG Phenotype, |
Sarah AlSubhi,Amal AlHashem,Anas AlAzami,Kalthoum Tlili,Saad AlShahwan,Dirk Lefeber,Fowzan S. Alkura |
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Abstract
ALG9-CDG is one of the less frequently reported types of CDG. Here, we summarize the features of six patients with ALG9-CDG reported in the literature and report the features of four additional patients. The patients presented with drug-resistant infantile epilepsy, hypotonia, dysmorphic features, failure to thrive, global developmental disability, and skeletal dysplasia. One patient presented with nonimmune hydrops fetalis. A brain MRI revealed global atrophy with delayed myelination. Exome sequencing identified a novel homozygous mutation c.1075G>A, p.E359K of the ALG9 gene. The results of our analysis of these patients expand the knowledge of ALG9-CDG phenotype.
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书目名称JIMD Reports, Volume 27影响因子(影响力)
书目名称JIMD Reports, Volume 27影响因子(影响力)学科排名
书目名称JIMD Reports, Volume 27网络公开度
书目名称JIMD Reports, Volume 27网络公开度学科排名
书目名称JIMD Reports, Volume 27被引频次
书目名称JIMD Reports, Volume 27被引频次学科排名
书目名称JIMD Reports, Volume 27年度引用
书目名称JIMD Reports, Volume 27年度引用学科排名
书目名称JIMD Reports, Volume 27读者反馈
书目名称JIMD Reports, Volume 27读者反馈学科排名
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