For The Want of a Nail … Trace Elements in Health and Disease
Owen M. Rennert, Wai-Yee Chan in Metabolism of Trace Metals in Man, 2017
The transmembrane behavior of copper in biological systems has not been well characterized. There is a fascinating human sex-linked disorder of copper metabolism called Menkes’ disease.28 Male infants are born without the ability to absorb, distribute, and assimilate copper properly. As a result, growth and development are impaired, and they die before the age of 2 years. In a search for the cause and cure of this disease, a mutant mouse with a similar impairment of copper metabolism was studied.29 By feeding the copper-nitrilotriacetate (copper-NT A) complex to mutant pregnant mother mice, the lethal developmental defects in their offspring could be avoided. Neither copper salts fed to the mothers nor copper-NTA fed to the pups were effective. These experiments suggest that the mutant lacks a complexing agent which mobilizes and circulates copper.
Diseases of the Nervous System
George Feuer, Felix A. de la Iglesia in Molecular Biochemistry of Human Disease, 2020
Menkes’ disease is characterized by peculiar hair (kinky-hair syndrome), neurological impairment, and severe mental retardation. The cerebral cortex and white matter are extensively degenerated. Copper levels are low in the liver and brain, and high in other tissues. It is likely that the disease is due to defects in the homeostatic control of copper metabolism. There is a relative deficiency of copper-dependent enzymes related to abnormal and metallothionein gene regulation in response to copper.358 In Menkes’ disease, metallothionein synthesis is defective, which binds copper, and other metallothionein binding metals (mercury, cadmium, zinc) are increased. Abnormalities include increased levels of serum lipids.72
Radiological Mimickers of Physical Child Abuse
B. G. Brogdon, Tor Shwayder, Jamie Elifritz in Child Abuse and Its Mimics in Skin and Bone, 2012
A neurodegenerative disorder first described in 1962, Menkes disease is an x-linked recessive inherited disease of copper metabolism.9 Deficiency of copper leads to various neurologic, hematologic, dermatologic, and musculoskeletal abnormalities. In Menkes disease, copper deficiency is secondary to faulty intestinal copper absorption. Laboratory evaluation of copper and ceruloplasmin is possible; however, these values are often low in normal newborns for the first 2–3 weeks of life. Hair abnormalities are the best-known trait of Menkes (Figures 3.13 and 3.14). Patients also display characteristic facies, various degrees of mental retardation, bladder diverticulae, and skin and joint laxity.10
Impaired copper transport in schizophrenia results in a copper-deficient brain state: A new side to the dysbindin story
Published in The World Journal of Biological Psychiatry, 2020
Kirsten E. Schoonover, Stacy L. Queern, Suzanne E. Lapi, Rosalinda C. Roberts
Copper plays a key role in development and homeostatic function and is crucial for many cellular functions including monoamine metabolism, mitochondrial activity and myelination (Sato et al. 1994). While copper and its enzymes are found outside of the brain, we will focus on brain. Copper dysfunction results in Wilson’s or Menkes disease, characterised by copper toxicity or deficiency, respectively (Wilson 1934; Menkes et al. 1962). Cellular copper is highly regulated, as free copper can induce oxidative stress and cellular damage (Halliwell and Gutteridge 2007). During normal function, copper is taken from the bloodstream across the blood–brain barrier (BBB) into astrocytes and then neurons via CTR1 at the plasma membrane (Scheiber et al. 2010). Once inside the cell, copper is bound by metallochaperones (Maryon et al. 2013) and delivered to the trans-Golgi network (TGN). ATP7A is located within the TGN (Yamaguchi et al. 1996) and distributes copper to metallochaperones (e.g., SCO1), which transport the copper to their needed location within the cell (e.g., mitochondria) ( Leary et al. 2007; Davies et al. 2013). CTR1 knockdown and/or loss results in developmental defects and lethality (Lee et al. 2001), and total loss of ATP7A results in Menkes disease and lethality (Menkes et al. 1962), exemplifying the incredible importance of these transporters in homeostasis and function.
Oliver McFarlane syndrome: two new cases and a review of the literature
Published in Ophthalmic Genetics, 2021
Kristian Lisbjerg, Mette K. G. Andersen, Mette Bertelsen, Agnes G. Brost, Frederik F. Buchvald, Rikke B. Jensen, Anne-Marie Bisgaard, Thomas Rosenberg, Zeynep Tümer, Line Kessel
Parents noticed visual difficulties from the age of two. At the age of three years, the patient underwent an ophthalmological examination at which point poor visual acuity equivalent to 20/200 (binocular) and a pale fundus with peripheral pigmentations was noted. The signs of severe chorioretinal degeneration were confirmed with ff-ERG that showed extinguished dark-adapted single flash and only a slight residual flicker response indicating absent rod function and very limited cone function. Complete night blindness was reported. The diagnosis at this point was early-onset retinitis pigmentosa. Fundoscopic findings were described as choroideremia-like. Due to dysmorphic features (Figure 1), growth retardation, and retinal degeneration a syndrome was suspected, and in the following years several clinical investigations were performed in the pursuit of a more exact diagnose. Chromosome analysis showed a normal female karyotype, 46,XX. The hair was examined for suspected Menkes disease or trichothiodystrophy but with no conclusive findings. At the age of three, thyroidal parameters were normal and clonidine stimulation of growth hormone (GH) also showed a normal result. Growth retardation persisted and by the age of 10, treatment with GH was initiated and she ended up with an adult height of 158 cm.
Copper deficiency, a rare but correctable cause of pancytopenia: a review of literature
Published in Expert Review of Hematology, 2022
Nayha Tahir, Aqsa Ashraf, Syed Hamza Bin Waqar, Abdul Rafae, Leela Kantamneni, Taha Sheikh, Rafiullah Khan
Menkes disease, first described in 1962 by Menkes et al., is yet another, rare X-linked recessive disturbance in copper metabolism and distribution characterized by ATP7A mutation, which plays a pivotal role in axonal outgrowth, synapse integrity, and neuronal activation [11]. Like HA, Menkes also has variation in presentations and can range anywhere from mild mental retardation to severe neuropsychiatric debility. Any hematopoietic effects, though, are not reported in Menkes disease [6,8,11].
Related Knowledge Centers
- Copper Deficiency
- Hypothermia
- Muscle Tone
- Preterm Birth
- Hypotonia
- X-Linked Recessive Inheritance
- Failure to Thrive
- Child Development Stages
- Global Developmental Delay
- Seizure