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The Turkish Journal of Pediatrics 2022Hair microscopy is a fast and effortless diagnostic method for many diseases affecting hair in daily practice. Many diseases can present with hair shaft disorders in...
BACKGROUND
Hair microscopy is a fast and effortless diagnostic method for many diseases affecting hair in daily practice. Many diseases can present with hair shaft disorders in pediatric neurology practice.
METHODS
Children with pathological hair findings were included in our study. Microscopic evaluation of the hair was performed under light microscopy. The clinical findings, pathological hair shaft findings, laboratory tests, and final diagnosis of the patients were evaluated.
RESULTS
In our study, 16 patients with rare pathological hair findings were identified. Of these 16 patients, nine were diagnosed with giant axonal neuropathy, three with Griscelli syndrome, two with Menkes disease, and two with autosomal recessive woolly hair disease. In hair inspection, curly and tangled hair in patients with giant axonal neuropathy; silvery blond hair in patients with Griscelli syndrome; sparse, coarse, and light-colored hair in patients with Menkes disease; and hypotrichosis in patients with autosomal recessive woolly hair were remarkable findings. Dystrophic hair was detected in most of the patients on light microscopy. In addition, signs of trichorrhexis nodosa, tricoptylosis, and pili torti were found. In particular, pigment deposition in the hair shaft of two patients diagnosed with Griscelli syndrome and pili torti findings in two patients with Menkes disease were the most important findings suggestingthe diagnosis.
CONCLUSIONS
Detection of hair findings in the physical examination and performing light microscopic evaluation facilitates the diagnosis of rare diseases accompanied by hair findings. A hair examination should be performed as a part of physical and neurological examinationson eachpatient regardless of thecomplaint.
Topics: Humans; Child; Menkes Kinky Hair Syndrome; Giant Axonal Neuropathy; Hair; Hair Diseases; Nervous System Diseases; Primary Immunodeficiency Diseases; Amino Acid Metabolism, Inborn Errors
PubMed: 36583891
DOI: 10.24953/turkjped.2022.221 -
Clinical Genetics May 2023Known hereditary human diseases featuring impaired copper trafficking across cellular membranes involve ATP7A (Menkes disease, occipital horn disease, X-linked spinal...
Known hereditary human diseases featuring impaired copper trafficking across cellular membranes involve ATP7A (Menkes disease, occipital horn disease, X-linked spinal muscular atrophy type 3) and ATP7B (Wilson disease). Herein, we report a newborn infant of consanguineous parents with a homozygous pathogenic variant in a highly conserved sequence of SLC31A1, coding for the copper influx transporter 1, CTR1. This missense variant, c.236T > C, was detected by whole exome sequencing. The infant was born with pulmonary hypoplasia and suffered from severe respiratory distress immediately after birth, necessitating aggressive mechanical ventilation. At 2 weeks of age, multifocal brain hemorrhages were diagnosed by cerebral ultrasound and magnetic resonance imaging, together with increased tortuosity of cerebral arteries. Ensuing seizures were only partly controlled by antiepileptic drugs, and the infant became progressively comatose. Laboratory investigations revealed very low serum concentrations of copper and ceruloplasmin. No hair shaft abnormalities were detected by dermatoscopy or light microscopic analyses of embedded hair shafts obtained at 4 weeks of life. The infant died after redirection of care and elective cessation of invasive mechanical ventilation at 1 month of age. This case adds SLC31A1 to the genes implicated in severe hereditary disorders of copper transport in humans.
Topics: Humans; Infant; Infant, Newborn; Ceruloplasmin; Copper; Copper Transporter 1; Copper-Transporting ATPases; Hepatolenticular Degeneration; Menkes Kinky Hair Syndrome; Mutation, Missense
PubMed: 36562171
DOI: 10.1111/cge.14289 -
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 -
BMJ Case Reports Apr 2022Menkes disease (MD) is an X linked recessive multi-systemic disorder of copper metabolism, resulting from an gene mutation. We report a male infant aged 4 months who... (Review)
Review
Menkes disease (MD) is an X linked recessive multi-systemic disorder of copper metabolism, resulting from an gene mutation. We report a male infant aged 4 months who presented with kinky hair, hypopigmented skin, epilepsy and delayed development. Magnetic resonance imaging (MRI) of brain demonstrated multiple tortuosities of intracranial vessels and brain atrophy. Investigation had showed markedly decreased serum copper and ceruloplasmin. The novel c.2172+1G>T splice-site mutation in the gene confirmed MD. He was treated with subcutaneous administration of locally prepared copper-histidine (Cu-His). Following the therapy, hair manifestation was restored and serum ceruloplasmin was normalised 1 month later. Despite the treatment, epilepsy, neurodevelopment and osteoporosis still progressed. He died from severe respiratory tract infection at the age of 9.5 months. These findings suggest that the benefit of Cu-His in our case is limited which might be related to severe presentations and degree of mutation.
Topics: Adenosine Triphosphatases; Cation Transport Proteins; Ceruloplasmin; Copper; Copper-Transporting ATPases; Epilepsy; Asia, Eastern; Histidine; Humans; Infant; Male; Menkes Kinky Hair Syndrome; Mutation; Organometallic Compounds; Peptide Fragments
PubMed: 35393273
DOI: 10.1136/bcr-2021-247937 -
Neuropediatrics Jun 2022
Topics: Cation Transport Proteins; Copper-Transporting ATPases; Humans; Menkes Kinky Hair Syndrome
PubMed: 35122229
DOI: 10.1055/a-1762-0354 -
Archives of Iranian Medicine Dec 2021
Topics: Copper; Humans; Menkes Kinky Hair Syndrome
PubMed: 35014241
DOI: 10.34172/aim.2021.138 -
Pharmaceutical Research Aug 2021Menkes disease is a rare hereditary disease in which systemic deficiency of copper due to mutation of the ATP7A gene causes severe neurodegenerative disorders. The...
PURPOSE
Menkes disease is a rare hereditary disease in which systemic deficiency of copper due to mutation of the ATP7A gene causes severe neurodegenerative disorders. The present parenteral drugs have limited efficacy, so there is a need for an efficacious drug that can be administered orally. This study focused on glyoxal-bis (N(4)-methylthiosemicarbazonato)-copper(II (CuGTSM), which has shown efficacy in macular mice, a murine model of Menkes disease, and examined its pharmacokinetics. In addition, nanosized CuGTSM (nCuGTSM) was prepared, and the effects of nanosizing on CuGTSM pharmacokinetics were investigated.
METHODS
CuGTSM or nCuGTSM (10 mg/kg) was administered orally to male macular mice or C3H/HeNCrl mice (control), and plasma was obtained by serial blood sampling. Plasma concentrations of CuGTSM and GTSM were measured by LC-MS/MS and pharmacokinetic parameters were calculated.
RESULTS
When CuGTSM was administered orally, CuGTSM and GTSM were both detected in the plasma of both mouse strains. When nCuGTSM was administered, the C was markedly higher, and the mean residence time was longer than when CuGTSM was administered for both CuGTSM and GTSM in both mouse strains. With macular mice, the AUC ratio (GTSM/CuGTSM) was markedly higher and the plasma CuGTSM concentration was lower than with C3H/HeNCrl mice when either CuGTSM or nCuGTSM was administered.
CONCLUSION
Absorption of orally administered CuGTSM was confirmed in macular mice, and the nano-formulation improved the absorption and retention of CuGTSM in the body. However, the plasma concentration of CuGTSM was lower in macular mice than in control mice, suggesting easier dissociation of CuGTSM.
Topics: Administration, Oral; Animals; Coordination Complexes; Disease Models, Animal; Male; Menkes Kinky Hair Syndrome; Mice; Mice, Inbred C3H; Particle Size; Thiosemicarbazones
PubMed: 34403032
DOI: 10.1007/s11095-021-03090-0 -
Genes May 2021Menkes disease (MD) is a rare and often lethal X-linked recessive syndrome, characterized by generalized alterations in copper transport and metabolism, linked to...
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. Trio-whole-exome sequencing (Trio-WES) analysis, plasma proteome screening, and blood cell migration assays were carried out. Trio-WES revealed a hemizygous change c.4190C > T (p.S1397F) in exon 22 of the gene. Compared with his parents and with child controls, 11 plasma proteins were upregulated and 59 downregulated in the patient. According to their biological processes, 42 (71.2%) of downregulated proteins had a participation in cellular transport. The immune system process was represented by 35 (59.3%) downregulated proteins ( = 9.44 × 10). Additional studies are necessary to validate these findings as hallmarks of MD.
Topics: Adolescent; Adult; Cell Movement; Copper-Transporting ATPases; Down-Regulation; Female; Humans; Immune System Phenomena; Infant; Male; Menkes Kinky Hair Syndrome; Mutation; Proteome; Proteomics; Up-Regulation; Exome Sequencing; Young Adult
PubMed: 34069220
DOI: 10.3390/genes12050744 -
Clinical Neuropathology 2021Menkes disease is a neurodegenerative metabolic disorder. It is an X-lined recessive disorder of copper metabolism. It is characterized by seizures, developmental delay...
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. We present such a genetically proven case of Menkes disease in a 17-month-old boy with seizures, cyanosis, and dyspnea. On evaluation, the child had low serum copper and ceruloplasmin. Magnetic resonance imaging revealed diffuse atrophy of the cerebrum, cerebellum with tortuosity of intracranial vessels. Autopsy confirmed the imaging findings along with dense gliosis, myelin loss, and significant loss of neurons in the cortex. Cerebellum showed aberrant dendritic arborization, somal sprouts, and axonal torpedoes within the Purkinje neurons. This report illustrates the classical presentation of in a genetically proven case of Menkes disease at autopsy, which has not been described in the recent literature.
Topics: Autopsy; Brain; Humans; Infant; Male; Menkes Kinky Hair Syndrome
PubMed: 34032205
DOI: 10.5414/NP301351 -
Actas Dermo-sifiliograficas Jul 2021
Topics: Hair Diseases; Humans; Infant; Menkes Kinky Hair Syndrome
PubMed: 33905712
DOI: 10.1016/j.ad.2020.08.013