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Adrenoleukodystrophy HELP
Based on 450 articles published since 2008
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These are the 450 published articles about Adrenoleukodystrophy that originated from Worldwide during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7 · 8 · 9 · 10 · 11 · 12 · 13 · 14 · 15 · 16 · 17 · 18
1 Guideline Newborn screening for X-linked adrenoleukodystrophy in New York State: diagnostic protocol, surveillance protocol and treatment guidelines. 2015

Vogel, B H / Bradley, S E / Adams, D J / D'Aco, K / Erbe, R W / Fong, C / Iglesias, A / Kronn, D / Levy, P / Morrissey, M / Orsini, J / Parton, P / Pellegrino, J / Saavedra-Matiz, C A / Shur, N / Wasserstein, M / Raymond, G V / Caggana, M. ·Newborn Screening Program, Wadsworth Center, New York State Department of Health, Albany, NY, USA. Electronic address: beth.vogel@health.ny.gov. · Newborn Screening Program, Wadsworth Center, New York State Department of Health, Albany, NY, USA. · Jacobs Equity Management Personalized Genomic Medicine Program, Goryeb Pediatrics Genetics and Metabolism, Morristown, NJ, USA. · Department of Pediatrics, University of Rochester Medical Center, Rochester, NY, USA. · Division of Genetics, Women and Children's Hospital of Buffalo, Buffalo, NY, USA. · New York Presbyterian Morgan Stanley Children's Hospital, New York, NY, USA. · New York Medical College, Valhalla, NY, USA. · Center for Inherited Medical Disorders, Children's Hospital at Montefiore, Bronx, NY, USA. · Division of Genetics, Stony Brook Long Island Children's Hospital, Stony Brook, NY, USA. · Department of Pediatrics, State University of New York Upstate Medical University, Syracuse, NY, USA. · Albany Medical Center, Albany, NY, USA. · Division of Medical Genetics, Division of Genomic Sciences, Mount Sinai Medical Center, New York, NY, USA. · Department of Neurology, University of Minnesota Medical Center, Minneapolis, MN, USA. ·Mol Genet Metab · Pubmed #25724074.

ABSTRACT: PURPOSE: To describe a diagnostic protocol, surveillance and treatment guidelines, genetic counseling considerations and long-term follow-up data elements developed in preparation for X-linked adrenoleukodystrophy (X-ALD) newborn screening in New York State. METHODS: A group including the director from each regional NYS inherited metabolic disorder center, personnel from the NYS Newborn Screening Program, and others prepared a follow-up plan for X-ALD NBS. Over the months preceding the start of screening, a series of conference calls took place to develop and refine a complete newborn screening system from initial positive screen results to long-term follow-up. RESULTS: A diagnostic protocol was developed to determine for each newborn with a positive screen whether the final diagnosis is X-ALD, carrier of X-ALD, Zellweger spectrum disorder, acyl CoA oxidase deficiency or D-bifunctional protein deficiency. For asymptomatic males with X-ALD, surveillance protocols were developed for use at the time of diagnosis, during childhood and during adulthood. Considerations for timing of treatment of adrenal and cerebral disease were developed. CONCLUSION: Because New York was the first newborn screening laboratory to include X-ALD on its panel, and symptoms may not develop for years, long-term follow-up is needed to evaluate the presented guidelines.

2 Editorial Optimizing Treatment for Cerebral Adrenoleukodystrophy in the Era of Gene Therapy. 2017

Engelen, Marc. ·From the Academisch Medisch Centrum-Emma Children's Hospital, Amsterdam. ·N Engl J Med · Pubmed #28976819.

ABSTRACT: -- No abstract --

3 Editorial The ABCD's of 5'-adenosine monophosphate-activated protein kinase and adrenoleukodystrophy. 2016

Weidling, Ian / Swerdlow, Russell H. ·University of Kansas Alzheimer's Disease Center, Kansas City, Kansas, USA. · Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas, USA. · Department of Neurology, University of Kansas Medical Center, Kansas City, Kansas, USA. · Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, Kansas, USA. ·J Neurochem · Pubmed #26990533.

ABSTRACT: This Editorial highlights a study by Singh and coworkers in the current issue of Journal of Neurochemistry, in which the authors present additional evidence that AMPKα1 is reduced in X-linked adrenoleukodystrophy (X-ALD). They make a case for increasing AMPKα1 activity for therapeutic purposes in this disease, and indicate how this goal may be achieved. Read the highlighted article 'Metformin-induced mitochondrial function and ABCD2 up regulation in X-linked adrenoleukodystrophy involves AMP activated protein kinase' on page 86.

4 Editorial Do we need a new look in the definition of X-linked recessive disorders? 2012

Lopes-Cendes, Iscia. · ·Arq Neuropsiquiatr · Pubmed #22836450.

ABSTRACT: -- No abstract --

5 Editorial Turning skin into brain: using patient-derived cells to model X-linked adrenoleukodystrophy. 2011

Parent, Jack M. · ·Ann Neurol · Pubmed #21905077.

ABSTRACT: -- No abstract --

6 Editorial [Ten years of gene therapy: thoughts and perspectives]. 2010

Cavazzana-Calvo, Marina / Hacein-Bey-Abina, Salima / Fischer, Alain. · ·Med Sci (Paris) · Pubmed #20188032.

ABSTRACT: -- No abstract --

7 Editorial Making rare diseases a public-health and research priority. 2008

Anonymous2120601. · ·Lancet · Pubmed #18555895.

ABSTRACT: -- No abstract --

8 Review Expanding the concept of peroxisomal diseases and efficient diagnostic system in Japan. 2019

Takashima, Shigeo / Saitsu, Hirotomo / Shimozawa, Nobuyuki. ·Division of Genomics Research, Life Science Research Center, Gifu University, Gifu, Japan. · Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu, Japan. · Division of Genomics Research, Life Science Research Center, Gifu University, Gifu, Japan. nshim@gifu-u.ac.jp. ·J Hum Genet · Pubmed #30237433.

ABSTRACT: The concept of peroxisomal diseases is expanding because of improvements in diagnostic technology based on advanced biochemical analysis and development of next-generation sequencing. For quicker and more accurate diagnosis of as many patients as possible, we developed a new diagnostic system combining the conventional diagnostic system and comprehensive mutational analysis by whole-exome sequencing in Japan. Adrenoleukodystrophy (ALD) is the most common peroxisomal disease. In the cerebral type of ALD, hematopoietic stem cell transplantation is the only treatment in the early stage, and thus prompt diagnosis will improve the prognosis of affected patients. Furthermore, it is also important to identify pre-symptomatic patients by family analysis of probands by providing appropriate disease information and genetic counseling, which will also lead to early intervention. Here, we summarize current information related to peroxisomal diseases and ALD and introduce our efficient diagnostic system for use in Japan, which resulted in the diagnosis of 73 Japanese patients with peroxisome biogenesis disorders, 16 with impaired β-oxidation of fatty acids, three with impaired etherphospholipid biosynthesis, and 191 Japanese families with ALD so far.

9 Review [Biogenesis, the Function of Peroxisomes, and Their Role in Genetic Disease: With a Focus on the ABC Transporter]. 2018

Imanaka, Tsuneo. ·Department of Biological Chemistry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama. ·Yakugaku Zasshi · Pubmed #30068848.

ABSTRACT:  Peroxisomes are organelles that are present in almost all eukaryotic cells. These organelles were first described in 1954, in the cytoplasm of the proximal tubule cells in the mouse kidney, using electron microscopy by Rhodin and referred to as "microbodies". Then, de Duve and Baudhuin isolated microbodies from rat liver using density gradient centrifugation, defined the microbodies as membrane-bound organelles containing several H

10 Review Leukodystrophy: Basic and Clinical. 2017

Raymond, Gerald V. ·Pediatric Neurology, University of Minnesota Medical Center, Minneapolis, MN, 55455, USA. gvraymon@umn.edu. · Department of Neurology, University of Minnesota Medical Center, MMC-295, 516 Delaware St, SE, Minneapolis, MN, 55455, USA. gvraymon@umn.edu. ·Adv Neurobiol · Pubmed #28674989.

ABSTRACT: Leukodystrophies are serious, progressive, genetic disorders of CNS myelin. They may result from abnormalities of the oligodendrocyte or any of the other of myriad of supporting cells or tissues. With recent developments in neuroimaging, their presence is becoming increasingly noted even in situations where they were not suspected. More importantly, new genetic tools have improved our ability to diagnose. An understanding of pathogenesis is still evolving, but it is expected that this will assist in developing targeted therapies for these devastating disorders.

11 Review Therapeutic strategies in adrenoleukodystrophy. 2017

Turk, Bela R / Moser, Ann B / Fatemi, Ali. ·Kennedy Krieger Institute, Johns Hopkins Medical Institutions, The Moser Center for Leukodystrophies, Baltimore, USA. · Kennedy Krieger Institute, Johns Hopkins Medical Institutions, The Moser Center for Leukodystrophies, Baltimore, USA. fatemi@kennedykrieger.org. ·Wien Med Wochenschr · Pubmed #28493141.

ABSTRACT: Adrenoleukodystrophy (ALD) is an X‑linked hereditary disorder due to mutations of the ABCD1 gene, which encodes a peroxisomal transport protein necessary for very long-chain fatty acid degradation (VLCFA). Toxic accumulation thereof is associated with a proinflammatory state and eventual cell death in multiple tissues. ALD may manifest either as a fatal, rapidly progressive demyelinating disease in boys and adult men, or as a slowly progressive adult-onset long-tract myelopathy along with peripheral neuropathy. Our understanding of manifold mechanisms implicated in the disease pathology is currently incomplete, as neither genotype-phenotype correlation nor the trigger for cerebral disease has been described. Therapy objectives are therefore broadly aimed at correcting either the gene mutation or downstream molecular effects, such as oxidative stress. Advancements in disease detection, including the newly implemented newborn screening in the US and imaging modalities, allow for more timely intervention in the form of hematopoietic stem cell transplantation (HSCT), which may only be performed in early cerebral disease states.

12 Review ABC Transporter Subfamily D: Distinct Differences in Behavior between ABCD1-3 and ABCD4 in Subcellular Localization, Function, and Human Disease. 2016

Kawaguchi, Kosuke / Morita, Masashi. ·Department of Biological Chemistry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan. ·Biomed Res Int · Pubmed #27766264.

ABSTRACT: ATP-binding cassette (ABC) transporters are one of the largest families of membrane-bound proteins and transport a wide variety of substrates across both extra- and intracellular membranes. They play a critical role in maintaining cellular homeostasis. To date, four ABC transporters belonging to subfamily D have been identified. ABCD1-3 and ABCD4 are localized to peroxisomes and lysosomes, respectively. ABCD1 and ABCD2 are involved in the transport of long and very long chain fatty acids (VLCFA) or their CoA-derivatives into peroxisomes with different substrate specificities, while ABCD3 is involved in the transport of branched chain acyl-CoA into peroxisomes. On the other hand, ABCD4 is deduced to take part in the transport of vitamin B

13 Review Regulation of Oligodendrocyte Differentiation and Myelination by Nuclear Receptors: Role in Neurodegenerative Disorders. 2016

Sandoval-Hernández, Adrián / Contreras, María José / Jaramillo, Jenny / Arboleda, Gonzalo. ·Grupo de Neurociencias y Muerte Celular, Facultad de Medicina e Instituto de Genética, Universidad Nacional de Colombia, Bogotá, Colombia. · Grupo de Neurociencias y Muerte Celular, Facultad de Medicina e Instituto de Genética, Universidad Nacional de Colombia, Bogotá, Colombia. gharboledab@unal.edu.co. · Departamento de Patología, Facultad de Medicina, Universidad Nacional de Colombia, Bogotá, Colombia. gharboledab@unal.edu.co. ·Adv Exp Med Biol · Pubmed #27714695.

ABSTRACT: During development and through adulthood, differentiation of diverse cell types is controlled by specific genetic and molecular programs for which transcription factors are master regulators of gene expression. Here, we present an overview of the role of nuclear receptors and their selective pharmacological modulators in oligodendrocytes linage, their role in myelination and remyelination and their potential use as a therapeutic strategy for demyelinating diseases. We discuss several aspects of nuclear receptors including: (1) the biochemistry of nuclear receptors superfamily; (2) their role on stem cells physiology, focusing in differentiation and cell removal; (3) the role of nuclear receptor in the oligodendrocytes cell linage, from oligodendrocyte progenitors cells to mature myelinating cells; and (4) the therapeutics opportunities of nuclear receptors for specific demyelinating diseases.

14 Review Adrenoleukodystrophy - neuroendocrine pathogenesis and redefinition of natural history. 2016

Kemp, Stephan / Huffnagel, Irene C / Linthorst, Gabor E / Wanders, Ronald J / Engelen, Marc. ·Department of Pediatrics, Academisch Medisch Centrum, University of Amsterdam Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. · Genetic Metabolic Diseases, Academisch Medisch Centrum, University of Amsterdam Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. · Pediatric Neurology, Academisch Medisch Centrum, University of Amsterdam Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. · Endocrinology and Metabolism, Academisch Medisch Centrum, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. ·Nat Rev Endocrinol · Pubmed #27312864.

ABSTRACT: X-Linked adrenoleukodystrophy (ALD) is a peroxisomal metabolic disorder with a highly complex clinical presentation. ALD is caused by mutations in the ABCD1 gene, which leads to the accumulation of very long-chain fatty acids in plasma and tissues. Virtually all men with ALD develop adrenal insufficiency and myelopathy. Approximately 60% of men develop progressive cerebral white matter lesions (known as cerebral ALD). However, one cannot identify these individuals until the early changes are seen using brain imaging. Women with ALD also develop myelopathy, but generally at a later age than men and adrenal insufficiency or cerebral ALD are very rare. Owing to the multisystem symptomatology of the disease, patients can be assessed by the paediatrician, general practitioner, endocrinologist or a neurologist. This Review describes current knowledge on the clinical presentation, diagnosis and treatment of ALD, and highlights gaps in our knowledge of the natural history of the disease owing to an absence of large-scale prospective cohort studies. Such studies are necessary for the identification of new prognostic biomarkers to improve care for patients with ALD, which is particularly relevant now that newborn screening for ALD is being introduced.

15 Review Neurodevelopmental Outcome after Hematopoietic Cell Transplantation in Inborn Errors of Metabolism: Current Considerations and Future Perspectives. 2016

Boelens, Jaap Jan / van Hasselt, Peter M. ·Pediatric Blood and Marrow Transplantation Program, University Medical Center Utrecht, Utrecht, The Netherlands. · Sylvia Toth Center, University Medical Center Utrecht, Utrecht, The Netherlands. ·Neuropediatrics · Pubmed #27308871.

ABSTRACT: Inborn errors of metabolism (IEM) comprise an assorted group of inherited diseases, some of which are due to disordered lysosomal or peroxisomal function and some of which might be improved following hematopoietic cell transplantation (HCT). In these disorders the onset in infancy or early childhood is typically accompanied by rapid deterioration, resulting in early death in the more severe phenotypes. Timely diagnosis and immediate referral to an IEM specialist are essential steps in optimal management. Treatment recommendations are based on the diagnosis, its phenotype, rate of progression, prior extent of disease, family values, and expectations, and the risks and benefits associated with available therapies, including HCT. International collaborative efforts are of utmost importance in determining outcomes of therapy for these rare diseases, and have improved those outcomes significantly over the last decades. In this review, we will focus on the neurodevelopmental outcomes after HCT in IEM, providing an international perspective on progress, limitations, and future directions.

16 Review Endocrine Dysfunction in X-Linked Adrenoleukodystrophy. 2016

Burtman, Elizabeth / Regelmann, Molly O. ·Division of Pediatric Endocrinology and Diabetes, Kravis Children's Hospital, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1616, New York, NY 10029, USA. · Division of Pediatric Endocrinology and Diabetes, Kravis Children's Hospital, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1616, New York, NY 10029, USA. Electronic address: molly.regelmann@mountsinai.org. ·Endocrinol Metab Clin North Am · Pubmed #27241966.

ABSTRACT: X-linked adrenoleukodystrophy (X-ALD) is caused by mutations in the ABCD1 gene and leads to an elevation of very-long-chain fatty acids (VLCFA). The accumulation of the VLCFA and the associated oxidative stress can present with a spectrum of significant neurologic disease, adrenal insufficiency, and testicular dysfunction in males with ABCD1 gene mutations. Much of the published literature for X-ALD has focused on the associated devastating progressive neurologic conditions. The purpose of this review is to summarize the concerns for endocrine dysfunction associated with X-ALD and provide guidance for monitoring and management of adrenal insufficiency.

17 Review Clinical and Biochemical Pitfalls in the Diagnosis of Peroxisomal Disorders. 2016

Klouwer, Femke C C / Huffnagel, Irene C / Ferdinandusse, Sacha / Waterham, Hans R / Wanders, Ronald J A / Engelen, Marc / Poll-The, Bwee Tien. ·Department of Pediatric Neurology, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. · Laboratory Genetic Metabolic Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. ·Neuropediatrics · Pubmed #27089543.

ABSTRACT: Peroxisomal disorders are a heterogeneous group of genetic metabolic disorders, caused by a defect in peroxisome biogenesis or a deficiency of a single peroxisomal enzyme. The peroxisomal disorders include the Zellweger spectrum disorders, the rhizomelic chondrodysplasia punctata spectrum disorders, X-linked adrenoleukodystrophy, and multiple single enzyme deficiencies. There are several core phenotypes caused by peroxisomal dysfunction that clinicians can recognize. The diagnosis is suggested by biochemical testing in blood and urine and confirmed by functional assays in cultured skin fibroblasts, followed by mutation analysis. This review describes the phenotype of the main peroxisomal disorders and possible pitfalls in (laboratory) diagnosis to aid clinicians in the recognition of this group of diseases.

18 Review Hopes, Promises, and Future Directions of Gene and Cell Therapies in France. 2016

Cartier, Nathalie / Cordelier, Pierre. ·Coeditors. ·Hum Gene Ther · Pubmed #26886830.

ABSTRACT: -- No abstract --

19 Review Novel Therapeutic Targets and Drug Candidates for Modifying Disease Progression in Adrenoleukodystrophy. 2016

Pujol, Aurora. ·Laboratory of Neurometabolic Diseases and Pathologic Anatomy Service, Institute of Neuropathology, Bellvitge Biomedical Research Institute (IDIBELL)-Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat and Center for Biomedical Research on Rare Diseases (CIBERER), U759, ISCIII, and Catalan Institution of Research and Advanced Studies (ICREA), Barcelona, Spain. ·Endocr Dev · Pubmed #26684655.

ABSTRACT: X-linked adrenoleukodystrophy (X-ALD) is the most frequent inherited monogenic demyelinating disease. It is often lethal and currently lacks a satisfactory therapy. The disease is caused by loss of function of the ABCD1 gene, a peroxisomal ATP-binding cassette transporter, resulting in the accumulation of very-long-chain fatty acids (VLCFA) in organs and plasma. Recent findings on pathomechanisms of the peroxisomal neurometabolic disease X-ALD have provided important clues on therapeutic targets. Here we describe the impact of chronic redox imbalance caused by the excess VLCFA on mitochondrial biogenesis and respiration, and explore the consequences on the protein quality control systems essential for cell survival, such as the proteasome and autophagic flux. Defective proteostasis, together with mitochondrial malfunction, is a hallmark of the most prevalent neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, and of the aging process. Thus, we discuss molecular targets and emerging treatment options that may be common to both multifactorial neurodegenerative disorders and X-ALD. New-generation antioxidants, some of them mitochondrial targeted, mitochondrial biogenesis boosters such as pioglitazone and resveratrol, and the mTOR inhibitor temsirolimus hold promise as disease-modifying therapies.

20 Review Gene Therapy for Rare Central Nervous System Diseases Comes to Age. 2016

Aubourg, Patrick. ·INSERM U1169, Department of Pediatric Neurology, Bicêtre Hospital, and Paris-Sud University, Le Kremlin-Bicêtre, France. ·Endocr Dev · Pubmed #26684481.

ABSTRACT: Gene therapy for rare inherited neurologic diseases has entered the clinics. One strategy relies upon the replacement of brain microglia using hematopoietic stem cell gene therapy with lentiviral vectors. Therapeutic success using this approach has been obtained in X-linked adrenoleukodystrophy and metachromatic leukodystrophy. The other strategy relies upon the intracerebral administration of adeno-associated virus vectors encoding lysosomal enzymes. Therapeutic trials are ongoing in Batten's disease, metachromatic leukodystrophy, and Sanfilippo type A and B diseases.

21 Review Oxidative Stress in Patients with X-Linked Adrenoleukodystrophy. 2016

Deon, Marion / Marchetti, Desirèe P / Donida, Bruna / Wajner, Moacir / Vargas, Carmen. ·Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. marion_deon@yahoo.com.br. · Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre (HCPA), Rua Ramiro Barcelos, 2350, Porto Alegre, RS, CEP 90035-003, Brazil. marion_deon@yahoo.com.br. · Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. · Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre (HCPA), Rua Ramiro Barcelos, 2350, Porto Alegre, RS, CEP 90035-003, Brazil. · Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. crvargas@hcpa.edu.br. · Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. crvargas@hcpa.edu.br. · Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre (HCPA), Rua Ramiro Barcelos, 2350, Porto Alegre, RS, CEP 90035-003, Brazil. crvargas@hcpa.edu.br. ·Cell Mol Neurobiol · Pubmed #26169524.

ABSTRACT: X-linked adrenoleukodystrophy (X-ALD) is the most frequent peroxisomal disorder that is characterized by progressive demyelination of the white matter, adrenal insufficiency, and accumulation of very long-chain fatty acids in body fluid and tissues. This disorder is clinically heterogeneous with seven different phenotypes in male patients and five phenotypes in female carriers. An ultimate treatment for X-ALD is not available. Depending on the rate of the disease progression and the degree of an individual handicap, special needs and challenges vary greatly. The exact mechanisms underlying the pathophysiology of this multifactorial neurodegenerative disorder remains obscure. Previous studies has been related oxidative stress with the pathogenesis of several disease that affecting the central nervous system, such as neurodegenerative disease, epilepsy, multiple sclerosis, Alzheimer, and Parkinson diseases. In addition, oxidative damage has been observed in various in vivo and in vitro studies with inborn errors of metabolism, including X-ALD. In this context, this review is focused on oxidative stress in X-ALD, with emphasis on studies using biological samples from patients affected by this disease.

22 Review Expanded newborn screening by mass spectrometry: New tests, future perspectives. 2016

Ombrone, Daniela / Giocaliere, Elisa / Forni, Giulia / Malvagia, Sabrina / la Marca, Giancarlo. ·Newborn screening, Clinical Chemistry and Pharmacology Lab, Meyer Children's University Hospital, Viale Pieraccini 24, Florence, 50139, Italy. · Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Viale Pieraccini 6, Florence, 50139, Italy. ·Mass Spectrom Rev · Pubmed #25952022.

ABSTRACT: Tandem mass spectrometry (MS/MS) has become a leading technology used in clinical chemistry and has shown to be particularly sensitive and specific when used in newborn screening (NBS) tests. The success of tandem mass spectrometry is due to important advances in hardware, software and clinical applications during the last 25 years. MS/MS permits a very rapid measurement of many metabolites in different biological specimens by using filter paper spots or directly on biological fluids. Its use in NBS give us the chance to identify possible treatable metabolic disorders even when asymptomatic and the benefits gained by this type of screening is now recognized worldwide. Today the use of MS/MS for second-tier tests and confirmatory testing is promising especially in the early detection of new disorders such as some lysosomal storage disorders, ADA and PNP SCIDs, X-adrenoleucodistrophy (X-ALD), Wilson disease, guanidinoacetate methyltransferase deficiency (GAMT), and Duchenne muscular dystrophy. The new challenge for the future will be reducing the false positive rate by using second-tier tests, avoiding false negative results by using new specific biomarkers and introducing new treatable disorders in NBS programs.

23 Review Role of family D ATP-binding cassette transporters (ABCD) in cancer. 2015

Hlaváč, Viktor / Souček, Pavel. ·Department of Toxicogenomics, National Institute of Public Health, Prague, Czech Republic viktor.hlavac@szu.cz. · Department of Toxicogenomics, National Institute of Public Health, Prague, Czech Republic. ·Biochem Soc Trans · Pubmed #26517907.

ABSTRACT: ATP-binding cassette (ABC) transporters, belonging to the family D, are expressed in peroxisomes, endoplasmic reticulum or lysosomes. ABCD transporters play a role in transport of lipids, bile acids and vitamin B12 and associate with peroxisomal disorders. ABCD1 performs transport of coenzyme A esters of very-long-chain fatty acids (VLCFA) in peroxisomes and a number of mutations in ABCD1 gene were linked to an X-linked adrenoleucodystrophy (X-ALD). The role of ABCD transporters in tumour growth has not been studied in detail, but there is some evidence that ABCDs levels differ between undifferentiated stem or tumour cells and differentiated cells suggesting a possible link to tumorigenesis. In this mini-review, we discuss the available information about the role of ABCD transporters in cancer.

24 Review Oxidative stress, mitochondrial and proteostasis malfunction in adrenoleukodystrophy: A paradigm for axonal degeneration. 2015

Fourcade, Stéphane / Ferrer, Isidre / Pujol, Aurora. ·Neurometabolic Diseases Laboratory, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Hospitalet de Llobregat, 08908 Barcelona, Spain; Institut of Neuropathology, Pathologic Anatomy Service, Bellvitge Biomedical Research Institute, IDIBELL-Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, 08908 Barcelona, Spain; Center for Biomedical Research on Rare Diseases (CIBERER), U759, ISCIII, Spain. Electronic address: sfourcade@idibell.cat. · Institut of Neuropathology, Pathologic Anatomy Service, Bellvitge Biomedical Research Institute, IDIBELL-Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, 08908 Barcelona, Spain; Center for Biomedical Research on Neurodegenerative Diseases (CIBERNED), Spain. · Neurometabolic Diseases Laboratory, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Hospitalet de Llobregat, 08908 Barcelona, Spain; Institut of Neuropathology, Pathologic Anatomy Service, Bellvitge Biomedical Research Institute, IDIBELL-Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, 08908 Barcelona, Spain; Center for Biomedical Research on Rare Diseases (CIBERER), U759, ISCIII, Spain; Catalan Institution of Research and Advanced Studies (ICREA), Barcelona 08010, Catalonia, Spain. Electronic address: apujol@idibell.cat. ·Free Radic Biol Med · Pubmed #26073123.

ABSTRACT: Peroxisomal and mitochondrial malfunction, which are highly intertwined through redox regulation, in combination with defective proteostasis, are hallmarks of the most prevalent multifactorial neurodegenerative diseases-including Alzheimer's (AD) and Parkinson's disease (PD)-and of the aging process, and are also found in inherited conditions. Here we review the interplay between oxidative stress and axonal degeneration, taking as groundwork recent findings on pathomechanisms of the peroxisomal neurometabolic disease adrenoleukodystrophy (X-ALD). We explore the impact of chronic redox imbalance caused by the excess of very long-chain fatty acids (VLCFA) on mitochondrial respiration and biogenesis, and discuss how this impairs protein quality control mechanisms essential for neural cell survival, such as the proteasome and autophagy systems. As consequence, prime molecular targets in the pathogenetic cascade emerge, such as the SIRT1/PGC-1α axis of mitochondrial biogenesis, and the inhibitor of autophagy mTOR. Thus, we propose that mitochondria-targeted antioxidants; mitochondrial biogenesis boosters such as the antidiabetic pioglitazone and the SIRT1 ligand resveratrol; and the autophagy activator temsirolimus, a derivative of the mTOR inhibitor rapamycin, hold promise as disease-modifying therapies for X-ALD.

25 Review Genetic forms of adrenal insufficiency. 2015

Brett, Elise M / Auchus, Richard J. · ·Endocr Pract · Pubmed #25667374.

ABSTRACT: OBJECTIVE: The American Association of Clinical Endocrinologists Adrenal Scientific Committee has developed a series of articles to update members on the genetics of adrenal diseases. METHODS: Case presentation, discussion of literature, table, and bullet point conclusions. RESULTS: The genetic mutations associated with several familial causes of adrenal insufficiency have now been identified. The most common ones that will be discussed here include Allgrove syndrome, adrenoleukodystrophy, adrenal hypoplasia congenita, autoimmune polyglandular syndrome type 1, congenital adrenal hyperplasia (CAH), lipoid CAH, and familial glucocorticoid deficiency. Although these diseases most commonly present in childhood, some rarely present in adulthood, and thus all endocrinologists must be familiar with these syndromes. Some patients only develop glucocorticoid deficiency, and others have both glucocorticoid and mineralocorticoid deficiency. These diseases may be associated with other conditions, especially neurologic disease, hypogonadism, or dermatologic problems. Diagnosis is suspected based on clinical presentation and laboratory findings. Gene testing may be necessary for confirmation of a diagnosis and/or screening of family members. CONCLUSION: This article briefly reviews the various familial adrenal insufficiency syndromes and the specific associated gene defects.

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