1,563 results match your criteria Menkes Disease

Copper nutrition and biochemistry and human (patho)physiology.

James F Collins

Adv Food Nutr Res 2021 12;96:311-364. Epub 2021 Apr 12.

Food Science and Human Nutrition Department, University of Florida, Gainesville, FL, United States. Electronic address:

The essential trace mineral copper plays important roles in human physiology and pathophysiology. Disruption of copper homeostasis may underlie the development of ischemic heart disease, and connective tissue and neurodegenerative disorders. Copper also likely participates in the host response to bacterial infection and is further implicated more broadly in regulating immunity. Read More

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Whole-Exome Sequencing, Proteome Landscape, and Immune Cell Migration Patterns in a Clinical Context of Menkes Disease.

Genes (Basel) 2021 May 14;12(5). Epub 2021 May 14.

Department of Histology, Universidad Autónoma de Nuevo León, Facultad de Medicina, Monterrey 64460, Mexico.

Menkes disease (MD) is a rare and often lethal X-linked recessive syndrome, characterized by generalized alterations in copper transport and metabolism, linked to mutations in the ATPase copper transporting α () gene. Our objective was to identify genomic alterations and circulating proteomic profiles related to MD assessing their potential roles in the clinical features of the disease. We describe the case of a male patient of 8 months of age with silvery hair, tan skin color, hypotonia, alterations in neurodevelopment, presence of seizures, and low values of plasma ceruloplasmin. Read More

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Neuropathological findings in a 17-month-old boy with kinky hair due to Menkes disease.

Clin Neuropathol 2021 May 25. Epub 2021 May 25.

Menkes disease is a neurodegenerative metabolic disorder. It is an X-lined recessive disorder of copper metabolism. It is characterized by seizures, developmental delay with loss of achieved milestones, along with skin and hair changes. Read More

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Genetic causes of fractures and subdural hematomas: fact versus fiction.

Pediatr Radiol 2021 May 17;51(6):1029-1043. Epub 2021 May 17.

George Washington University School of Medicine and Health Sciences, Washington, DC, USA.

Genetic disorders are in the differential diagnosis when young children present with unexplained fractures or intracranial hemorrhage. For medical and legal reasons, it is imperative to make the correct diagnosis and provide clear, evidence-based explanations of how alternative diagnoses were ruled out. A genetics consultation in cases of suspected child physical abuse should synthesize the history of present illness, medical history, family history, physical examination, and radiologic and laboratory findings in consultation with other specialists. Read More

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Occipital Horn Syndrome as a Result of Splice Site Mutations in . No Activity of Splice Variants Missing Exon 10 or Exon 15.

Front Mol Neurosci 2021 21;14:532291. Epub 2021 Apr 21.

Department of Biology, University of Copenhagen, Copenhagen, Denmark.

Disease-causing variants in lead to two different phenotypes associated with copper deficiency; a lethal form called Menkes disease (MD), leading to early death, and a much milder form called occipital horn syndrome (OHS). Some investigators have proposed that an transcript missing exon 10 leads to a partly active protein product resulting in the OHS phenotype. Here, we describe an individual with OHS, a biology professor, who survived until age 62 despite a splice site mutation, leading to skipping of exon 15. Read More

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ATP7A-Regulated Enzyme Metalation and Trafficking in the Menkes Disease Puzzle.

Biomedicines 2021 Apr 6;9(4). Epub 2021 Apr 6.

Department of Biology and Biological Engineering, Chalmers University of Technology, 41296 Gothenburg, Sweden.

Copper is vital for numerous cellular functions affecting all tissues and organ systems in the body. The copper pump, ATP7A is critical for whole-body, cellular, and subcellular copper homeostasis, and dysfunction due to genetic defects results in Menkes disease. ATP7A dysfunction leads to copper deficiency in nervous tissue, liver, and blood but accumulation in other tissues. Read More

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Hair Abnormalities: Key to Suspecting Menkes Disease.

Actas Dermosifiliogr 2021 Apr 24. Epub 2021 Apr 24.

Departamento de Dermatología, Hospital Universitario Son Espases, Palma de Mallorca, España.

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Copper Toxicity Associated With an ATP7A-Related Complex Phenotype.

Pediatr Neurol 2021 Jun 26;119:40-44. Epub 2021 Mar 26.

Neuromuscular Unit, Department of Pediatric Neurology, Hospital Sant Joan de Déu and Institut de Recerca Sant Joan de Déu, Barcelona, Spain; Center for Biomedical Research Network on Rare Diseases (CIBERER), ISCIII, Madrid, Spain.

Background: The ATP7A gene encodes a copper transporter whose mutations cause Menkes disease, occipital horn syndrome (OHS), and, less frequently, ATP7A-related distal hereditary motor neuropathy (dHMN). Here we describe a family with OHS caused by a novel mutation in the ATP7A gene, including a patient with a comorbid dHMN that worsened markedly after being treated with copper histidinate.

Methods: We studied in detail the clinical features of the patients and performed a genomic analysis by using TruSight One Expanded Sequencing Panel. Read More

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[Pedigree study and analysis of ATP7A gene variants in three children with Menkes disease].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 Feb;38(2):108-111

Department of Pediatric Neurology, the Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.

Objective: To explore the genetic basis for three children with Menkes disease.

Methods: The patients were subjected to next-generation sequencing (NGS) to detect potential variants of the ATP7A gene. Suspected variants were verified by Sanger sequencing of their family members and 200 healthy individuals. Read More

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February 2021

Antioxidant vs. Prooxidant Properties of the Flavonoid, Kaempferol, in the Presence of Cu(II) Ions: A ROS-Scavenging Activity, Fenton Reaction and DNA Damage Study.

Int J Mol Sci 2021 Feb 5;22(4). Epub 2021 Feb 5.

Institute of Physical Chemistry and Chemical Physics, Faculty of Chemical and Food Technology, Slovak University of Technology, 812 37 Bratislava, Slovakia.

Kaempferol is a flavonoid that occurs in tea and in many vegetables and fruits, including broccoli, cabbage, beans, grapes, apples, and strawberries. The efficacy of Kaempferol has been demonstrated in the treatment of breast, esophageal, cervical, ovarian, and liver cancers and leukemia, which very likely arises from its prooxidant properties and the activation of pro-apoptotic pathways. Indeed, this matter has already been the focus of a number of published studies and reviews. Read More

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February 2021

COMMD1, a multi-potent intracellular protein involved in copper homeostasis, protein trafficking, inflammation, and cancer.

J Trace Elem Med Biol 2021 May 7;65:126712. Epub 2021 Jan 7.

Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Department of Clinical Sciences of Companion Animals, 3584 CM, Utrecht, the Netherlands. Electronic address:

Copper is a trace element indispensable for life, but at the same time it is implicated in reactive oxygen species formation. Several inherited copper storage diseases are described of which Wilson disease (copper overload, mutations in ATP7B gene) and Menkes disease (copper deficiency, mutations in ATP7A gene) are the most prominent ones. After the discovery in 2002 of a novel gene product (i. Read More

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The M1311V variant of ATP7A is associated with impaired trafficking and copper homeostasis in models of motor neuron disease.

Neurobiol Dis 2021 02 24;149:105228. Epub 2020 Dec 24.

Department of Neurobiology, Barrow Neurological Institute, Phoenix, AZ 85013, USA. Electronic address:

Disruption in copper homeostasis causes a number of cognitive and motor deficits. Wilson's disease and Menkes disease are neurodevelopmental disorders resulting from mutations in the copper transporters ATP7A and ATP7B, with ATP7A mutations also causing occipital horn syndrome, and distal motor neuropathy. A 65 year old male presenting with brachial amyotrophic diplegia and diagnosed with amyotrophic lateral sclerosis (ALS) was found to harbor a p. Read More

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February 2021

Copper Dyshomeostasis in Neurodegenerative Diseases-Therapeutic Implications.

Int J Mol Sci 2020 Dec 4;21(23). Epub 2020 Dec 4.

Department of Cellular Signalling, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawińskiego Street, 02-106 Warsaw, Poland.

Copper is one of the most abundant basic transition metals in the human body. It takes part in oxygen metabolism, collagen synthesis, and skin pigmentation, maintaining the integrity of blood vessels, as well as in iron homeostasis, antioxidant defense, and neurotransmitter synthesis. It may also be involved in cell signaling and may participate in modulation of membrane receptor-ligand interactions, control of kinase and related phosphatase functions, as well as many cellular pathways. Read More

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December 2020

Golgi-Dependent Copper Homeostasis Sustains Synaptic Development and Mitochondrial Content.

J Neurosci 2021 01 18;41(2):215-233. Epub 2020 Nov 18.

Departments of Cell Biology, Emory University, Atlanta, Georgia 30322

Rare genetic diseases preponderantly affect the nervous system causing neurodegeneration to neurodevelopmental disorders. This is the case for both Menkes and Wilson disease, arising from mutations in ATP7A and ATP7B, respectively. The ATP7A and ATP7B proteins localize to the Golgi and regulate copper homeostasis. Read More

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January 2021

Effect of homeostatic iron regulator protein gene mutation on Wilson's disease clinical manifestation: original data and literature review.

Int J Neurosci 2020 Nov 18:1-7. Epub 2020 Nov 18.

Second Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland.

Objective: Wilson's disease (WD) is a hereditary disorder of copper metabolism. The metabolic pathways of copper and iron are interrelated. Our goal was to determine the frequency of the two most common mutations in the coding region of the human iron homeostatic protein gene () in Europe: C282Y (rs1800562) and H63D (rs1799945) in WD patients, as well as to analyze their relation with WD phenotypic traits. Read More

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November 2020

Investigation of Genetic Modifiers of Copper Toxicosis in Labrador Retrievers.

Life (Basel) 2020 Oct 31;10(11). Epub 2020 Oct 31.

Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 108, 3584 CM Utrecht, The Netherlands.

Copper toxicosis is a complex genetic disorder in Labrador retrievers characterized by hepatic copper accumulation eventually leading to liver cirrhosis. The variation of hepatic copper levels in Labrador retrievers has been partly explained by mutations in c.980C>T and c. Read More

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October 2020

ATP7A mutation with occipital horns and distal motor neuropathy: A continuum.

Eur J Med Genet 2020 Dec 31;63(12):104087. Epub 2020 Oct 31.

Service de génétique, CLAD Ouest, CHU Rennes, Rennes, France; Service de génétique, CRDI, CHU Rennes, Rennes, France.

ATP7A-related copper transport disorders are classically separated in three pathologies according to their severity, all inherited in an X-linked recessive manner: Menkes disease (MD, OMIM #309400) which represent more than 90% of cases; occipital Horn Syndrome (OHS, OMIM #304150) and ATP7A-related distal motor neuropathy also named X-linked distal spinal muscular atrophy-3 (SMAX3, OMIM #300489) (Kennerson et al., 2010). Although there is no clear cut correlation between Cu and ceruloplasmin levels in ATP7A related disorders, these three entities probably represent a continuum partly depending on residual functional ATP7A protein (Møller, 2015). Read More

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December 2020

Repurposing elesclomol, an investigational drug for the treatment of copper metabolism disorders.

Vishal M Gohil

Expert Opin Investig Drugs 2021 Jan 5;30(1):1-4. Epub 2020 Nov 5.

Department of Biochemistry and Biophysics, Texas A&M University , College Station, TX, USA.

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January 2021

ATP7A Clinical Genetics Resource - A comprehensive clinically annotated database and resource for genetic variants in ATP7A gene.

Comput Struct Biotechnol J 2020 2;18:2347-2356. Epub 2020 Sep 2.

CSIR Institute of Genomics and Integrative Biology, Mathura Road, Delhi 110 025, India.

ATP7A is a critical copper transporter involved in Menkes Disease, Occipital horn Syndrome and X-linked distal spinal muscular atrophy type 3 which are X linked genetic disorders. These are rare diseases and their genetic epidemiology of the diseases is unknown. A number of genetic variants in the genes have been reported in published literature as well as databases, however, understanding the pathogenicity of variants and genetic epidemiology requires the data to be compiled in a unified format. Read More

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September 2020

Laparoscopic patch repair of a Morgagni hernia in Menkes disease.

Asian J Endosc Surg 2020 Sep 10. Epub 2020 Sep 10.

Pediatric Surgery Unit, Azienda Ospedaliera Universitaria Policlinico Umberto I, Sapienza University of Rome, Rome, Italy.

The association between Morgagni hernia and Menkes disease has not yet been described. Here, we report such a rare association in an 8-year-old boy who presented with subocclusive symptoms. He successfully underwent laparoscopic repair with a patch. Read More

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September 2020

The physiological function of copper, the etiological role of copper excess and deficiency

Orv Hetil 2020 08;161(35):1488-1496

Általános Orvostudományi Kar, I. Patológiai és Kísérleti Rákkutató Intézet,Semmelweis Egyetem, Budapest, Üllői út 26., 1085.

Copper is an essential micronutrient for the human body, taking part in several metabolic processes. It is required for the terminal oxidation, the elimination of free radicals, the proper functioning of iron metabolism, the synthesis of hormones, neurotransmitters and the stabilization of the extracellular matrix. Copper is a two-faced element. Read More

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LC-ICP-MS method for the determination of "extractable copper" in serum.

Metallomics 2020 09;12(9):1348-1355

Elemental Scientific, Inc., 7277 World Communications Dr., Omaha, NE, USA.

Copper is an essential element for biological functions within humans and animals. There are several known diseases associated with Cu deficiency or overload, such as Menkes disease and Wilson disease, respectively. A common clinical method for determining extractable Cu levels in serum, which is thought to be potentially dangerous if in excess, is to subtract the value of tightly incorporated Cu in ceruloplasmin from total serum Cu. Read More

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September 2020

Wilson's Disease: Diagnosis of Wilson's Disease in Ethiopian Young Sisters.

Case Rep Med 2020 24;2020:7650170. Epub 2020 Jul 24.

Department of Internal Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia.

Background: Wilson's disease is an inherited autosomal recessive disorder of copper metabolism. Clinical signs, biochemical parameters, histologic findings, and/or ATP7B genetic testing are required to diagnose Wilson's disease. . Read More

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Targeted next generation sequencing for newborn screening of Menkes disease.

Mol Genet Metab Rep 2020 Sep 21;24:100625. Epub 2020 Jul 21.

Parabase Genomics, Inc., Boston, MA, United States of America.

Purpose: Population-based newborn screening (NBS) allows early detection and treatment of inherited disorders. For certain medically-actionable conditions, however, NBS is limited by the absence of reliable biochemical signatures amenable to detection by current platforms. We sought to assess the analytic validity of an targeted next generation DNA sequencing assay as a potential newborn screen for one such disorder, Menkes disease. Read More

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September 2020

Case 280: Trichopoliodystrophy.

Radiology 2020 Aug;296(2):463-467

From the Department of Diagnostic and Interventional Radiology, Kwong Wah Hospital, 25 Waterloo Road, Yau Ma Tei, Hong Kong (K.F.K.F., Y.Y.K., W.S.M.); and Department of Radiology, Hong Kong Children's Hospital, Hong Kong (Y.L.E.K.).

HistoryAn 8-month-old previously healthy boy was referred to our institution by the maternal child health center for progressive truncal hypotonia and developmental delay. This infant was born after an uncomplicated pregnancy with no perinatal complications. He was delivered at full term via spontaneous vaginal delivery. Read More

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[Menkes disease, a diagnosis to consider in case of severe epilepsy with hyperlactacidemia: a case report].

Ann Biol Clin (Paris) 2020 08;78(4):441-445

Département de biochimie et hormonologie, CHU Montpellier, France, PhyMedExp, Université de Montpellier (UM), Inserm, CNRS, Montpellier, France.

Menkes disease is an X-linked recessive disorder affecting copper metabolism due to an inactivating mutation of ATP7A gene. This result in loss of copper intestinal absorption, tissue deficiency and failure in multiple essential copper-enzyme systems such as the cytochrome c oxidase. Symptoms usually occur during the first months of life with neurological signs such as epilepsy associated to other signs among them typical hair appearance. Read More

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Cancer Pro-oxidant Therapy Through Copper Redox Cycling: .

Manuel Rieber

Curr Pharm Des 2020 ;26(35):4461-4466

IVIC, Cancer Cell Biology Laboratory, CMBC, Caracas 1020A, Venezuela.

Background: Copper (Cu) is a transition metal active in Fenton redox cycling from reduced Cu+ and H2O2, to oxidized Cu2+ and the hydroxyl radical (·OH) highly reactive oxygen species (ROS). At homeostatic Cu levels, ROS promote cell proliferation, migration, angiogenesis, and wound repair. To limit ROS toxicity, cells use Cu-dependent chaperone proteins, Cu-binding ceruloplasmin, and Cu-modulated enzymes like superoxide dismutases (SOD) like SOD1 and SOD3 to scavenge excess superoxide anions which favour Cu+ reduction, and mitochondrial cytochrome c oxidase, important in aerobic energy production. Read More

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February 2021

Low function of natural killer cells in treated classic Menkes disease.

Turk J Pediatr 2020 ;62(3):498-500

Division of Pediatric Neurology, University of South Alabama Children's and Women's Hospital, Mobile, Alabama.

Background: Menkes disease (MD) is a rare lethal X-linked, multisystem disorder of copper metabolism resulting from mutations in the ATP7A gene. Features such as Ehlers- Danlos syndrome, trichopoliodystrophy, urologic and skeletal changes have been reported. We present a case of classic MD treated with copper infusions who suffered from persistent natural killer (NK) cell dysfunction. Read More

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January 2020