Menkes Disease: Infant Copper Hereditary Deficiency

Menkes disease (kinky hair disease or Menkes kinky hair syndrome) rare genetic pediatric disease (1 In 100,000 3) caused by a defective gene (ATP7A) that regulates the metabolism or amount of copper in the body, primarily affects male infant beginning of infancy. 1, 2 The neurodegenerative disease first described in 1962 by Menkes et al. 9 According to the National Institute of Health (NIH), Menkes disease listed as a rare disease, affects less than 200,000 people in the United States. 13 The mutated gene ATP7A distributes copper in the human body disproportionately: Brain and other tissues of the body receive low level of copper and accumulation occurs in the small intestines and kidneys. The low amount of copper reduces enzymes (mutated gene fails to absorb copper from food which supply certain enzymes 4 ) in the human body necessary for structure and function of bone, skin, nervous system and blood vessels (arteries). 3 Symptoms of Menkes disease detected during the first 2 - 3 months of infancy: Males experience significant medical problems including hypothermia (body temperature drops below normal to sustain bodily functions and metabolism. 5), delayed development, mental retardation, experience seizures, and physical changes of their face and hair (patients have brittle hair) 6 Also, in the bone at the base of the skull (occipital bone) accumulation of wedge - shaped calcium deposits and loose skin and joints. 3 Females primarily have changes in hair and skin color. 6 The prognosis for Menkes disease is very poor and most patients die within the first ten years of their life. 2

Males have 'X' and 'Y' chromosomes ("A Chromosome is a single large macromolecule of DNA and constitutes a physically organized form of DNA in a cell" 8) and females have two 'X' chromosomes. 7 Menkes disease linked to a disorder located on the 'X' chromosome. In males when one 'X' chromosome is mutated sufficient to cause kinky hair disease. In females the mutation must be present in both 'X' chromosomes for the disorder to be present, rare occurrence. The characteristic of Menkes disease X - linked inheritance prevents fathers from passing X - linked chromosome traits to their sons. Females are carriers of this trait. 19 Approximately two-thirds of Menkes disease is linked to hereditary and one-third cases result from new mutations in the gene. 3

The diagnosis of Menkes disease by genetic testing may show mutation in the ATP7A gene. 19 Examination under the microscope of hair appears to both whitish and kinked (Woolly hair but less tightly coiled within one area or more of the scalp. 14, 17). Also, observation for symptoms previously mentioned, as well slow growth, bleeding in the brain, premature birth, and feeding difficulties. 15 , 20

Menkes disease can be treated or treatment may provide some benefit (Minimize the severity of physical handicaps that will develop later in life. 12) if the disorder is diagnosed early, before irreversible brain damage occurs or physical defects manifest. The disease prohibits normal absorption of copper through the gastrointestinal tract (Starting from the mouth, food enters and travels through a process being digested, extracted energy, nutrients provided and finally a discharge of waste or excretion 10). Copper must be delivered to brain cells and made accessible for the use by enzymes in the body by an alternative intravenous (copper histidine) or oral copper replacement, avoids absorption through the gastrointestinal tract. 11 Also, when Menkes disease is diagnosed during pregnancy (prenatally), treatment is available by injections of copper histidine under the skin.12 The dosage of copper histidine various from 200 - 1000 µg once a day or 2 -3 times/week. 21 Copper histidine appears to be effective increasing life expectancy from three to thirteen years of age. 16 However, uncertain if copper treatment may be linked to low blood pressure in response to changing body position (orthostatic hypotension), an enlarge spleen and ballooning of an artery in the abdomen or from Menkes disease as reported studying a boy diagnosed with this disorder. Consult geneticists (specialist in hereditary disease) for further information and treatment regarding Menkes disease. 12

Dr. Ed Harris researcher at Texas Agriculture Experiment Station said Menkes disease would most likely be treated with gene therapy linked to a functioning gene into a patient. Also he said: "But we're doing the basic research now, and the hurdles that must be overcome for its success." 18

References:

1) NINDS Menkes Disease Information Page http://www.ninds.nih.gov/disorders/menkes/menkes.htm

2) Menkes disease http://en.wikipedia.org/wiki/Menkes_disease

3) Menkes Syndrome http://ghr.nlm.nih.gov/condition=menkessyndrome

4) ATP7A http://ghr.nlm.nih.gov/gene=atp7a

5) Hypothermia http://en.wikipedia.org/wiki/Hypothermia

6) Copper Histidine Therapy for Menkes Diseases http://www.clinicaltrials.gov/ct/gui/show/NCT00001262?order=5

7) X Chromosome http://en.wikipedia.org/wiki/X_chromosome

8) Chromosome http://en.wikipedia.org/wiki/Chromosome

9) Menkes Disease http://www.emedicine.com/neuro/topic569.htm

10) gastroinestinal tract http://www.answers.com/topic/gastrointestinal-tract?cat=health

11) Copper Histidine Therapy for Menkes Diseases http://www.clinicaltrials.gov/ct/gui/show/NCT00001262?order=5

12) MENKES' DISEASE http://www.mothernature.com/Library/Ency/Index.cfm/id/1237000

13) Menkes Disease http://www.wrongdiagnosis.com/m/menkes_disease/intro.htm

14) Kinked hair http://www.keratin.com/ag/ag005.shtml

15) Diagnostic Tests for Menkes Disease http://www.wrongdiagnosis.com/m/menkes_disease/tests.htm

16) Menkes syndrome http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowSection&rid=gnd.section.230

17) Menkes disease http://www.gfmer.ch/genetic_diseases_v2/gendis_detail_list.php?cat3=198

18) Deadly copper disease in infants targeted http://www.eurekalert.org/pub_releases/2001-10/tau-dcd100301.php

19) Menkes Syndrome http://www.walgreens.com/library/contents.jsp?doctype=1&docid=001160

20) Menkes Syndrome http://health.nytimes.com/health/guides/disease/menkes-syndrome/overview.html21) Treatment of Menkes Disease with Parenteral Copper Histidine http://www.indianpediatrics.net/feb2002/feb-183-185.htm