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Asian Journal of Endoscopic Surgery Jul 2021The 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...
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. The patch was fixed to the anterior abdominal wall by using transfascial sutures with extracorporeal knot tying and to the remaining edges of the diaphragmatic defect by using intracorporeal suturing and spiral tacks. At the 2-year follow-up, the child remained recurrence-free and without gastrointestinal symptoms. The potential relationship between the two conditions and the controversial use of spiral tacks to affix the mesh to the diaphragm are also discussed.
Topics: Child; Diaphragm; Hernias, Diaphragmatic, Congenital; Herniorrhaphy; Humans; Laparoscopy; Male; Menkes Kinky Hair Syndrome; Surgical Mesh
PubMed: 32914541
DOI: 10.1111/ases.12865 -
Pediatrics International : Official... 2023
Topics: Humans; Menkes Kinky Hair Syndrome; Vascular Diseases; Thrombosis; Heart Diseases; Jugular Veins; Dilatation, Pathologic
PubMed: 37888729
DOI: 10.1111/ped.15667 -
International Journal of Molecular... Sep 2022Kidneys play an especial role in copper redistribution in the organism. The epithelial cells of proximal tubules perform the functions of both copper uptake from the...
Decreased Expression of the Gene and Cytoplasmic Relocalization of Membrane CTR1 Protein in Renal Epithelial Cells: A Potent Protective Mechanism against Copper Nephrotoxicity in a Mouse Model of Menkes Disease.
Kidneys play an especial role in copper redistribution in the organism. The epithelial cells of proximal tubules perform the functions of both copper uptake from the primary urine and release to the blood. These cells are equipped on their apical and basal membrane with copper transporters CTR1 and ATP7A. mutant mice displaying a functional dysfunction of ATP7A are an established model of Menkes disease. These mice exhibit systemic copper deficiency despite renal copper overload, enhanced by copper therapy, which is indispensable for their life span extension. The aim of this study was to analyze the expression of and genes (encoding CTR1/CTR2 proteins) and the cellular localization of the CTR1 protein in suckling, young and adult mutants. Our results indicate that in the kidney of both intact and copper-injected 14-day-old mutants showing high renal copper content, CTR1 mRNA level is not up-regulated compared to wild-type mice given a copper injection. The expression of the gene in 45-day-old mice is even reduced compared with intact wild-type animals. In suckling and young copper-injected mutants, the CTR1 protein is relocalized from the apical membrane to the cytoplasm of epithelial cells of proximal tubules, the process which prevents copper transport from the primary urine and, thus, protects cells against copper toxicity.
Topics: Animals; Cation Transport Proteins; Cell Membrane; Copper; Copper Transporter 1; Copper-Transporting ATPases; Cytoplasm; Disease Models, Animal; Epithelial Cells; Gene Expression; Kidney Tubules, Proximal; Membrane Proteins; Menkes Kinky Hair Syndrome; Mice; Protein Transport; RNA, Messenger; SLC31 Proteins
PubMed: 36232742
DOI: 10.3390/ijms231911441 -
The Turkish Journal of Pediatrics 2020Menkes 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...
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.
CASE
A 2-year-old, Caucasian male child presented at 8-month-old of age with persistent hypotonia, kinky hair and developmental regression. Diagnosis of MD was based on low serum levels of copper [5 mg/dl (18-37)] and ceruloplasmin [18 ug/dl (75-153)] and gene-targeted deletion/duplication analysis performed by the reference laboratory. Brain MRI showed mild hypoplasia of the cerebellar vermis and vascular tortuosity typical of MD. Copper chloride treatment was immediately initiated. The child became more alert with excellent eye contact and purposeful movements. The child was hospitalized for recurrent respiratory infections, each time caused by enterovirus as confirmed by multiplex polymerase chain reaction (PCR). Extensive immunologic studies were negative, except for a severe NK cell dysfunction on multiple occasions (0.6 NK lytic Units; N > 2.6).
CONCLUSION
We postulate that NK cell dysfunction in a classic MD can be explained by the deficient incorporation of copper in the endoplasmic reticulum resulting in an abnormal Fenton chemistry within phagosomes.
Topics: Child, Preschool; Copper-Transporting ATPases; Humans; Infant; Killer Cells, Natural; Male; Menkes Kinky Hair Syndrome; Muscle Hypotonia; Mutation
PubMed: 32558428
DOI: 10.24953/turkjped.2020.03.021 -
Frontiers in Immunology 2019Neutrophil extracellular traps (NETs) contribute to pathological disorders, and their release was directly linked to numerous diseases. With intravital microscopy (IVM),...
Neutrophil extracellular traps (NETs) contribute to pathological disorders, and their release was directly linked to numerous diseases. With intravital microscopy (IVM), we showed previously that NETs also contribute to the pathology of systemic inflammation and are strongly deposited in liver sinusoids. Over a decade since NET discovery, still not much is known about the metabolic or microenvironmental aspects of their formation. Copper is a vital trace element essential for many biological processes, albeit its excess is potentially cytotoxic; thus, copper levels are tightly controlled by factors such as copper transporting ATPases, ATP7A, and ATP7B. By employing IVM, we studied the impact of copper on NET formation during endotoxemia in liver vasculature on two mice models of copper excess or deficiency, Wilson (ATP7B mutants) and Menkes (ATP7A mutants) diseases, respectively. Here, we show that respective ATP7 mutations lead to diminished NET release during systemic inflammation despite unaltered intrinsic capacity of neutrophils to cast NETs as tested . In Menkes disease mice, the effect is mostly due to diminished neutrophil infiltration of the liver as unmutated mice with a subchronic copper deficiency release even more NETs than their controls during endotoxemia, whereas in Wilson disease mice, excess copper directly diminishes the capacity to release NETs, and this was further confirmed by studies on isolated neutrophils co-cultured with exogenous copper and a copper-chelating agent. Taken together, the study extends our understanding on how microenvironmental factors affect NET release by showing that copper is not a prerequisite for NET release but its excess affects the trap casting by neutrophils.
Topics: Animals; Copper; Copper-Transporting ATPases; Disease Models, Animal; Extracellular Traps; Hepatolenticular Degeneration; Humans; Male; Menkes Kinky Hair Syndrome; Mice; Mice, Inbred C57BL; Neutrophil Infiltration; Neutrophils
PubMed: 32010131
DOI: 10.3389/fimmu.2019.03021 -
Zhonghua Yi Xue Yi Chuan Xue Za Zhi =... Apr 2020To carry out genetic testing for a male infant suspected for Menkes disease.
OBJECTIVE
To carry out genetic testing for a male infant suspected for Menkes disease.
METHODS
Genomic DNA of the proband and his parents were extracted and subjected to family trio whole exome sequencing (WES). Microduplication and microdeletion of the ATP7A gene were detected by multiplex ligation-dependent probe amplification (MLPA). Suspected variants were subjected to bioinformatic analysis and verified by Sanger sequencing.
RESULTS
The proband was found to harbor a de novo c.1870 -13T>G variation of the ATP7A gene, which may alter a splice site and affect its protein product.
CONCLUSION
The patient was diagnosed with Menkes disease due to the c.1870 -13T>G variant of the ATP7A gene. Whole exome sequencing of family trios is a powerful tool for the diagnosis of diseases with strong phenotypic heterogeneity.
Topics: Copper-Transporting ATPases; Genetic Testing; Humans; Infant; Male; Menkes Kinky Hair Syndrome; Multiplex Polymerase Chain Reaction; Mutation; Exome Sequencing
PubMed: 32219842
DOI: 10.3760/cma.j.issn.1003-9406.2020.04.029 -
Turkish Journal of Haematology :... Aug 2019
Topics: Bone Marrow; Child, Preschool; Erythroid Cells; Humans; Male; Menkes Kinky Hair Syndrome; Myeloid Cells; Vacuoles
PubMed: 29716882
DOI: 10.4274/tjh.galenos.2018.2018.0104 -
Scientific Reports Jan 2024Menkes disease is an X-linked disorder of copper metabolism caused by mutations in the ATP7A gene, and female carriers are usually asymptomatic. We describe a...
Menkes disease is an X-linked disorder of copper metabolism caused by mutations in the ATP7A gene, and female carriers are usually asymptomatic. We describe a 7-month-old female patient with severe intellectual disability, epilepsy, and low levels of serum copper and ceruloplasmin. While heterozygous deletion of exons 16 and 17 of the ATP7A gene was detected in the proband, her mother, and her grandmother, only the proband suffered from Menkes disease clinically. Intriguingly, X chromosome inactivation (XCI) analysis demonstrated that the grandmother and the mother showed skewing of XCI toward the allele with the ATP7A deletion and that the proband had extremely skewed XCI toward the normal allele, resulting in exclusive expression of the pathogenic ATP7A mRNA transcripts. Expression bias analysis and recombination mapping of the X chromosome by the combination of whole genome and RNA sequencing demonstrated that meiotic recombination occurred at Xp21-p22 and Xq26-q28. Assuming that a genetic factor on the X chromosome enhanced or suppressed XCI of its allele, the factor must be on either of the two distal regions derived from her grandfather. Although we were unable to fully uncover the molecular mechanism, we concluded that unfavorable switching of skewed XCI caused Menkes disease in the proband.
Topics: Humans; Infant; Female; Menkes Kinky Hair Syndrome; X Chromosome Inactivation; Copper; Chromosomes, Human, X; Mutation
PubMed: 38172222
DOI: 10.1038/s41598-023-50668-2 -
Brain & Development Nov 2019Menkes disease (MD) is a lethal infantile neurodegenerative disorder with X-linked inheritance, characterized by progressive neurodegenerative symptoms caused by...
Menkes disease (MD) is a lethal infantile neurodegenerative disorder with X-linked inheritance, characterized by progressive neurodegenerative symptoms caused by pathogenic variants in the ATP7A. Early diagnosis and treatment are important, although the diagnosis is difficult prior to 2 months of age. We present an unusually severe case of MD with skull fractures at the birth and repeated fractures during the neonatal period, with further examinations leading to diagnosis. The patient died due to hemorrhagic shock, due to multiple arterial occlusion despite initiation of copper-histidine therapy in early infancy. Bone fracture at birth and multiple arterial occlusion are very rare findings in MD. This unusual and severe presentation emphasizes the importance of early diagnosis and treatment. A congenital bone fracture should be considered as a possible presentation of MD, especially in cases without birth complications.
Topics: Arterial Occlusive Diseases; Cerebral Infarction; Fractures, Bone; Humans; Infant, Newborn; Male; Menkes Kinky Hair Syndrome
PubMed: 31279518
DOI: 10.1016/j.braindev.2019.06.005 -
Annales de Biologie Clinique Aug 2020Menkes 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...
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. We report the case of a 3 month-old infant hospitalized due to partial tonic-clonic seizures. Laboratory findings showed increased of lactates in blood and in cerebrospinal fluid. First screenings for infectious, metabolic and genetic causes were negative. After recurrence of multifocal seizures further investigations are made according to the presence of thick and tortuous hair. Low levels of ceruloplasmin and copper in plasma are in agreement with the suspected diagnosis of Menkes disease. Molecular analysis of the ATP7A gene confirmed the diagnosis with a non-sens mutation.
Topics: Diagnosis, Differential; Epilepsy; Humans; Hyperlactatemia; Infant; Male; Menkes Kinky Hair Syndrome; Severity of Illness Index
PubMed: 32633724
DOI: 10.1684/abc.2020.1566