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Genetics of Menkes Kinky Hair Disease Clinical Presentation

  • Author: Stephen G Kaler, MD, MPH; Chief Editor: Maria Descartes, MD  more...
 
Updated: Sep 08, 2015
 

History

The typical history of a patient with Menkes kinky hair disease (MKHD) includes healthy pregnancy and delivery. Birth frequently occurs several weeks in advance of the estimated date of confinement or due date.

  • Classic Menkes kinky hair disease often escapes attention in the neonatal period because of its very subtle manifestations in neonates. However, several nonspecific physical and metabolic findings are commonly cited when birth histories of these babies are reviewed.
    • These findings include premature labor and delivery, large cephalohematomas in individuals born by abdominal delivery, hypothermia that necessitates warming lights or an isolette, hypoglycemia for which early feeding or support with intravenous (IV) glucose is instituted, and jaundice that requires several days of phototherapy.
    • Pectus excavatum and inguinal or umbilical herniae are found at birth in some patients with Menkes kinky hair disease.
    • Occasionally, unusual hair pigmentation may suggest the diagnosis in newborns. However, the appearance of the hair is often unremarkable. As in healthy babies, newborns with Menkes kinky hair disease may exhibit no hair or have normally pigmented hair. The pili torti Menkes kinky hair disease on microscopic examination of hair from older patients with Menkes kinky hair disease is not usually evident in the hair of newborns with Menkes kinky hair disease.
  • Neurologically, newborns with Menkes kinky hair disease generally appear to be healthy. Excessive jitteriness was noted in one patient at age 1 week.
  • Transient neonatal hypothermia and hypoglycemia are not uncommon; however, infants with Menkes kinky hair disease appear essentially healthy at birth and for the first 4-6 weeks of life.
  • When the infant is aged approximately 2-2.5 months, the parents usually first suspect that something is wrong and voice their concerns to the healthcare provider.
  • A steady downward spiral continues clinically, with development of progressive hypotonia, seizures, failure to thrive, and appearance of the characteristic coarse wiry hair by the time the individual with Menkes kinky hair disease is aged 4-5 months.
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Physical

As noted previously, major clinical manifestations of persons with Menkes kinky hair disease include loss of early developmental milestones, truncal hypotonia, seizures, poor weight gain, abnormal hair, loose skin, pectus excavatum, and urinary bladder diverticula.

The severity widely varies in patients with Menkes kinky hair disease and certain disorders; although once considered distinct genetic entities, they most likely represent allelic variants.

  • Patients with the classic phenotype may differ in certain respects (eg, presence of functional vision, level of infant personal-social development, severity of seizures), but they invariably demonstrate profound hypotonia and motor impairment. In contrast, patients with variants of the classic phenotype demonstrate less severe overall developmental outcomes.
    • One such child evaluated at the NIH was aged approximately 7 months when developmental delay was first noted.
      • When aged 9 months, the child required surgery for bladder outlet obstruction due to massive diverticula.
      • He was diagnosed with Menkes kinky hair disease when aged 22 months.
      • When aged 27 months, he was able to sit alone, crawl, play with toys, indicate his needs, and voice approximately 20 words with poor articulation. He was ataxic with head bobbing and tremor, and his brain MRI exhibited mild cerebellar hypoplasia. He had normal findings on EEG and no clinical seizures. His growth exhibited height between the 25th and 50th percentile for age, with weight and head circumference both slightly below the fifth percentile. His biochemical parameters (eg, plasma copper, plasma catecholamines, copper accumulation in cultured fibroblasts) did not differ significantly from values in infants with classic Menkes kinky hair disease.
      • Apart from his asymmetric growth retardation and history of bladder diverticula, this patient resembles a reported example of mild Menkes kinky hair disease.
    • Another atypical patient has been reported in whom motor development was relatively better, ataxia less severe, and connective tissue problems more prominent than the initially reported mild patient.
    • Because the neurologic impairment is less profound, other patients with conditions such as these seem unlikely to be suspected of having a condition related to Menkes kinky hair disease. Of note, both of the patients reported above had pili torti, which aided in establishing their diagnosis.
  • Another probable Menkes variant is type IX Ehlers-Danlos syndrome, otherwise known as X-linked cutis laxa or occipital horn syndrome (OHS), in reference to the pathognomonic wedge-shaped calcification that forms within the trapezius and sternocleidomastoid muscles at their attachment to the occipital bone in affected individuals. See the image below.
    Adolescent patient with typical occipital horn synAdolescent patient with typical occipital horn syndrome. Note elbow dislocations and genu valgum. Radiographs exhibited bilateral occipital exostoses of the skull and club-shaped distal clavicles.
    See the list below:
    • This protuberance can be palpated in some patients and is demonstrable radiographically on Towne view or on appropriate sagittal CT scanning or MRI cuts. Radiologic abnormalities of the clavicles and long bones have also been noted.
    • Clinical findings include lax skin and joints, bladder diverticula, inguinal herniae, vascular tortuosity, and normal or slightly subnormal intelligence.
    • Biochemically, plasma copper and ceruloplasmin levels are in the low reference range, copper egress in cultured fibroblasts is impaired to the same degree as in classic Menkes kinky hair disease, and activity of fibroblast lysyl oxidase (LO) is markedly reduced.
    • Additionally, some patients have signs of autonomic dysfunction (eg, syncope, episodic diarrhea) suggestive of dopamine beta-hydroxylase (DBH) deficiency. Neurologic findings are otherwise essentially normal.
  • Other clinical variants have been reported that involve features of both the classic Menkes and the occipital horn phenotypes.
    • One kindred study included 4 males aged 15 months to 35 years who had low or low-normal plasma copper; abnormal plasma catecholamines; and a syndrome of mental retardation, childhood-onset seizures (aged 3-8 y), neuromuscular weakness, joint abnormalities, and bladder diverticula.
    • Occipital exostoses were detected in the 15-year-old patient during radiologic studies performed after a sudden cerebral hemorrhage.
    • The 35-year-old man developed seizures when aged 3-4 years and required vesicostomy when aged 9 years for bladder outflow problems caused by diverticula. He learned to walk with the aid of crutches. His elbows became dislocated. He had the estimated intellectual capacity of an individual aged 8 years, and his speech was extremely inarticulate. His size was that of a small adult.
    • The members of this family who were affected with Menkes kinky hair disease were found to have splice site mutations in the 3' region of the Menkes/OHS gene that impaired but did not eliminate proper RNA splicing; a similar type of splicing mutation was found in an unrelated patient with typical OHS.
    • In 1994, Kaler et al quantitated the amount of proper splicing in cultured cells associated with these mutations at approximately 20-30% of normal.[10]
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Causes

Mutations in the Menkes/OHS gene underlie both classic and milder phenotypes. The severity of mutations and amount of possible residual copper ATPase activity appear to be relevant to the variable clinical outcomes.[11] Secondary deficiencies of copper-dependent enzymes are believed to cause certain of the clinical manifestations, as reviewed earlier (see Pathophysiology).

  • Menkes/OHS gene: Location of the Menkes/OHS gene on the X chromosome was indicated by pedigree analysis from the time of its earliest descriptions.
    • Progressively refined localization to Xq13 was enabled by linkage studies and characterization of X chromosomal rearrangements in 2 unrelated patients.
    • Genomic DNA from the chromosomal breakpoint region was used to identify portions of the Menkes locus by screening complementary DNA (cDNA) libraries or by exon trapping.
    • The candidate gene thus identified was found to be expressed abnormally in more than 70% of patients with Menkes kinky hair disease who were studied, and gene deletions were detectable by Southern blotting in more than 15% of these patients.
    • The Menkes/OHS gene is expressed in all human tissues tested, with the liver being a prominent exception. The messenger RNA (mRNA) transcript is approximately 8.5 kilobases (kb), with a long 3' noncoding portion and a coding sequence of 4.5 kb.
    • The predicted gene product is a 1500–amino acid molecule that is similar to numerous ion-motive ATPase molecules, including a pair of copper-transporting ATPases (copA and copB) in the bacterium Enterococcus hirae, an intracellular copper transporter (CCC2) in Saccharomyces cerevisiae, and the Wilson disease gene product.
  • Menkes/OHS copper ATPase: A wide array of ion-motive ATPases has been characterized, and they are divided into 3 classes (ie, P, V, F).
    • The P-type ATPases, of which the Menkes gene product is an example, are so named because they form a covalently phosphorylated intermediate from transfer of the gamma-phosphate of ATP to a specific aspartate residue at the catalytic site of the protein.
    • V-type ATPases are those associated with vacuolar organelles (eg, lysosomes, endosomes, storage granules, Golgi vesicles).
    • The F-type ATPases are found in most bacteria and are associated with mitochondria in higher organisms.
    • The overall sequence similarity among prokaryotic and eukaryotic cation-transporting ATPases suggests that these proteins have been modified throughout evolution in response to the need for import and export of various cations across different cellular membranes.
    • P-type ATPases function in the regulation of intracellular ion concentrations. Those imbedded in plasma membranes function to extrude their respective ions from the cell. Other P-type ATPases are localized to the membranes of intracellular organelles (eg, sarcoplasmic reticulum, endoplasmic reticulum) and act to sequester ions within their lumens. Interaction with ATP at a specific site is believed to induce multiple conformational adjustments that reorient the molecule with respect to the membrane, creating channels for cation translocation from high-affinity binding sites on one membrane side to low-affinity binding domains oriented toward the other side. Alternative splicing that generates multiple isoforms with potential functional differences has been demonstrated for certain ATPases of this class.
  • Menkes gene product: In the Menkes gene product, the N-terminal portion has a distinctive recurring amino acid pattern, cysteine-X-serine-cysteine, which is comparable to putative metal binding sites in the bacterial ATPases involved in transport of copper, cadmium, and mercury, respectively. Hydrophobicity analysis indicates 6-8 transmembrane domains, and the predicted protein demonstrates all the other functional domains expected of P-type ATPases. The expression of the Menkes gene in nearly all human tissues, the severe consequences of impaired function (ie, MKHD) and the high degree of evolutionary conservation all indicate the fundamental importance of the copper transport process that this gene encodes.
    • With the discovery of the Menkes gene, investigating the basic cell biological defect in greater depth became possible. Elegant studies in several laboratories (ie, Camakaris, Francis, Gitlin, Glover, Mercer) localized the Menkes/OHS gene product to the trans-Golgi apparatus, where it is involved in the delivery of copper to copper-dependent enzymes processed in the secretory pathway of cells. In addition, the Menkes/OHS ATPase appears to relocate in response to increased copper exposure, moving to the plasma membrane of cells where it presumably functions as a pump directly mediating copper exodus from cells.
    • This model of the gene product's locations (trans-Golgi and plasma membrane) is consistent with the copper retention phenotype of cultured Menkes cells and with induction of metallothionein (MT) in these cells at much lower experimental copper exposures than in healthy cells.
      • MT, a cysteine-rich heavy metal–binding protein, may represent a secondary line of defense against the toxicity of high intracellular copper that is required sooner than usual in Menkes cells because of a defect in the primary regulatory mechanism (ie, removal of copper).
      • The efficiency with which MT performs its detoxifying role and the extremely avid binding of MT to copper restricts the availability of the metal to cytosolic copper enzymes (eg, Cu/Zn SOD), as well as those synthesized or located in cellular compartments. Under normal conditions, MT presumably helps maintain low intracellular levels of free copper while permitting activation of the copper enzymes. However, in Menkes kinky hair disease, chronic MT induction due to failure of normal copper transport disrupts this balance.
      • Failure to extrude copper from intestinal mucosal cells into the blood explains the accumulation of copper in these cells and the consequent reduced delivery of copper to the liver in individuals with Menkes kinky hair disease. Similarly, failed copper export by placental cells accounts for the placental copper accumulation observed in pregnancies affected by Menkes kinky hair disease and the low hepatic copper levels in fetuses with Menkes kinky hair disease. Failure of copper export by vascular endothelial and glial cells comprising the blood-brain barrier explains low copper levels and reduced copper enzyme activities in the brain. Because the Menkes gene is weakly expressed in the liver, this organ must possess alternative mechanisms for copper excretion (ie, Wilson copper ATPase) and thus does not manifest the copper accumulation, MT induction, or copper enzyme deficiencies found in other tissues.
  • Mutational analysis of the Menkes/OHS gene: Identification of the Menkes/OHS gene provided the opportunity for molecular analysis of patients with Menkes kinky hair disease. Before the genomic organization of the gene was characterized completely, the reverse transcription–polymerase chain reaction method (RT-PCR) offered a particularly useful approach to mutation analysis.
    • RT-PCR involves isolation of intact RNA from cultured fibroblasts or lymphoblasts and reverse transcription of the 8.5-kb Menkes message using oligodeoxythymidine as a primer. This reaction generates a full-length cDNA that is suitable as a template for PCR using gene-specific primers. The entire cDNA from patients with Menkes kinky hair disease thus may be obtained for direct sequence analysis.
    • Menkes/OHS gene mutation analysis by this method, and more recently from genomic DNA directly, has been conducted in several laboratories (ie, Horn, Kaler, Mercer, Ogawa), contributing important information about the molecular correlates of certain clinical and biochemical phenotypes and about functional aspects of this copper-ATPase. Molecular diagnosis also provides practical benefit to Menkes families with regard to detection of fetuses with Menkes kinky hair disease and females who are carriers.
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Contributor Information and Disclosures
Author

Stephen G Kaler, MD, MPH Head, Unit On Pediatric Genetics, Laboratory of Clinical Genomics and Clinical Director, Intramural Research Program, National Institute of Child Health & Human Development (NICHD), National Institutes of Health

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Margaret M McGovern, MD, PhD Professor and Chair of Pediatrics, Stony Brook University School of Medicine

Margaret M McGovern, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Chief Editor

Maria Descartes, MD Professor, Department of Human Genetics and Department of Pediatrics, University of Alabama at Birmingham School of Medicine

Maria Descartes, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics, American Medical Association, American Society of Human Genetics, Society for Inherited Metabolic Disorders, International Skeletal Dysplasia Society, Southeastern Regional Genetics Group

Disclosure: Nothing to disclose.

Additional Contributors

Christian J Renner, MD Consulting Staff, Department of Pediatrics, University Hospital for Children and Adolescents, Erlangen, Germany

Disclosure: Nothing to disclose.

Acknowledgements

I thank deeply the patients and families who have participated in our clinical trials and the members of my Section for their hard work and dedication to the aims of our laboratory.

References
  1. Møller LB, Hicks JD, Holmes CS, Goldstein DS, Brendl C, Huppke P, et al. Diagnosis of copper transport disorders. Curr Protoc Hum Genet. 2011 Jul. Chapter 17:Unit17.9. [Medline]. [Full Text].

  2. Kim YH, Lee R, Yoo HW, Yum MS, Bae SH, Chung SC, et al. Identification of a novel mutation in the ATP7A gene in a Korean patient with Menkes disease. J Korean Med Sci. 2011 Jul. 26(7):951-3. [Medline]. [Full Text].

  3. Datta AK, Ghosh T, Nayak K, Ghosh M. Menkes kinky hair disease: A case report. Cases J. 2008 Sep 18. 1(1):158. [Medline].

  4. Aldecoa V, Escofet-Soteras C, Artuch R, Ormazabal A, Gabau-Vila E, Martin-Martinez C. [Menkes disease: its clinical, biochemical and molecular diagnosis]. Rev Neurol. 2008 Apr 1-15. 46(7):446-7. [Medline].

  5. Danks DM, Campbell PE, Walker-Smith J, et al. Menkes' kinky-hair syndrome. Lancet. 1972 May 20. 1(7760):1100-2. [Medline].

  6. Danks DM, Cartwright E, Stevens BJ, Townley RR. Menkes' kinky hair disease: further definition of the defect in copper transport. Science. 1973 Mar 16. 179(78):1140-2. [Medline].

  7. Menkes JHM, Alter M, Steigleder GK. A sex-linked recessive disorder with retardation of growth, peculiar hair and focal cerebellar degeneration. Pediatrics. 1962. 29:764-769.

  8. Chelly J, Tumer Z, Tonnesen T, et al. Isolation of a candidate gene for Menkes disease that encodes a potential heavy metal binding protein. Nat Genet. 1993 Jan. 3(1):14-9. [Medline].

  9. Baerlocher K, Nadal D. [Menkes syndrome]. Ergeb Inn Med Kinderheilkd. 1988. 57:77-144. [Medline].

  10. Kaler SG. Menkes disease. Adv Pediatr. 1994. 41:263-304. [Medline].

  11. Kaler SG, Tang J, Donsante A, Kaneski CR. Translational read-through of a nonsense mutation in ATP7A impacts treatment outcome in Menkes disease. Ann Neurol. 2009 Jan. 65(1):108-13. [Medline].

  12. Donsante A, Yi L, Zerfas PM, Brinster LR, Sullivan P, Goldstein DS, et al. ATP7A gene addition to the choroid plexus results in long-term rescue of the lethal copper transport defect in a Menkes disease mouse model. Mol Ther. 2011 Dec. 19(12):2114-23. [Medline]. [Full Text].

  13. Sato R, Okutani K, Higashi T, Satou M, Fujimoto K, Okazaki K. [Case report : respiratory care for anesthesia in a patient with Menkes syndrome and micrognathia]. Masui. 2009 Jan. 58(1):103-5. [Medline].

  14. Passariello M, Almenrader N, Pietropaoli P. Anesthesia for a child with Menkes disease. Paediatr Anaesth. 2008 Dec. 18(12):1225-6. [Medline].

  15. Yamashita J, Yamakage M, Kawana S, Namiki A. Two cases of Menkes disease: airway management and dental fragility. Anaesth Intensive Care. 2009 Mar. 37(2):332-3. [Medline].

  16. [Guideline] Cunniff C. Prenatal screening and diagnosis for pediatricians. Pediatrics. 2004 Sep. 114(3):889-94. [Medline].

  17. Amaravadi R, Glerum DM, Tzagoloff A. Isolation of a cDNA encoding the human homolog of COX17, a yeast gene essential for mitochondrial copper recruitment. Hum Genet. 1997 Mar. 99(3):329-33. [Medline].

  18. Bennetts HW, Chapman FE. Copper deficiency in sheep in Western Australia: a preliminary account of the aetiology of enzootic ataxia of lambs and an anemia of ewes. Aust Vet J. 1937. 13:138-49.

  19. Camakaris J, Voskoboinik I, Mercer JF. Molecular mechanisms of copper homeostasis. Biochem Biophys Res Commun. 1999 Aug 2. 261(2):225-32. [Medline].

  20. Francis MJ, Jones EE, Levy ER, et al. A Golgi localization signal identified in the Menkes recombinant protein. Hum Mol Genet. 1998 Aug. 7(8):1245-52. [Medline].

  21. Grange DK, Kaler SG, Albers GM, et al. Severe bilateral panlobular emphysema and pulmonary arterial hypoplasia: unusual manifestations of Menkes disease. Am J Med Genet A. 2005 Dec 1. 139(2):151-5. [Medline].

  22. Guitet M, Campistol J, Medina M. [Menkes disease: experience in copper salts therapy]. Rev Neurol. 1999 Jul 16-31. 29(2):127-30. [Medline].

  23. Kaler SG. ATP7A-related copper transport diseases-emerging concepts and future trends. Nat Rev Neurol. 2011 Jan. 7(1):15-29. [Medline].

  24. Kaler SG. Diagnosis and therapy of Menkes syndrome, a genetic form of copper deficiency. Am J Clin Nutr. 1998 May. 67(5 Suppl):1029S-1034S. [Medline].

  25. Kaler SG. Menkes disease mutations and response to early copper histidine treatment. Nat Genet. 1996 May. 13(1):21-2. [Medline].

  26. Kaler SG. Metabolic and molecular bases of Menkes disease and occipital horn syndrome. Pediatr Dev Pathol. 1998 Jan-Feb. 1(1):85-98. [Medline].

  27. Kaler SG, Buist NR, Holmes CS, et al. Early copper therapy in classic Menkes disease patients with a novel splicing mutation. Ann Neurol. 1995 Dec. 38(6):921-8. [Medline].

  28. Kaler SG, Das S, Levinson B, et al. Successful early copper therapy in menkes disease associated with a mutant transcript containing a small In-frame deletion. Biochem Mol Med. 1996 Feb. 57(1):37-46. [Medline].

  29. Kaler SG, Gahl WA, Berry SA, et al. Predictive value of plasma catecholamine levels in neonatal detection of Menkes disease. J Inherit Metab Dis. 1993. 16(5):907-8. [Medline].

  30. Kaler SG, Gallo LK, Proud VK, et al. Occipital horn syndrome and a mild Menkes phenotype associated with splice site mutations at the MNK locus. Nat Genet. 1994 Oct. 8(2):195-202. [Medline].

  31. Kaler SG, Goldstein DS, Holmes C, et al. Plasma and cerebrospinal fluid neurochemical pattern in Menkes disease. Ann Neurol. 1993 Feb. 33(2):171-5. [Medline].

  32. Kaler SG, Holmes CS, Goldstein DS, Tang J, Godwin SC, Donsante A, et al. Neonatal diagnosis and treatment of Menkes disease. N Engl J Med. 2008 Feb 7. 358(6):605-14. [Medline]. [Full Text].

  33. Kaler SG, Schwartz JP. Expression of the Menkes disease homolog in rodent neuroglial cells. Neurosci Res Commun. 1998. 23:61-66.

  34. Kaler SG, Tumer Z. Prenatal diagnosis of Menkes disease. Prenat Diagn. 1998 Mar. 18(3):287-9. [Medline].

  35. Klomp LW, Lin SJ, Yuan DS et al. Identification and functional expression of HAH1, a novel human gene involved in copper homeostasis. J Biol Chem. 1997 Apr 4. 272(14):9221-6. [Medline].

  36. Kodama H, Murata Y, Kobayashi M. Clinical manifestations and treatment of Menkes disease and its variants. Pediatr Int. 1999 Aug. 41(4):423-9. [Medline].

  37. La Fontaine SL, Firth SD, Camakaris J, et al. Correction of the copper transport defect of Menkes patient fibroblasts by expression of the Menkes and Wilson ATPases. J Biol Chem. 1998 Nov 20. 273(47):31375-80. [Medline].

  38. Levinson B, Conant R, Schnur R, et al. A repeated element in the regulatory region of the MNK gene and its deletion in a patient with occipital horn syndrome. Hum Mol Genet. 1996 Nov. 5(11):1737-42. [Medline].

  39. Mercer JF, Livingston J, Hall B, et al. Isolation of a partial candidate gene for Menkes disease by positional cloning. Nat Genet. 1993 Jan. 3(1):20-5. [Medline].

  40. Moller LB, Tumer Z, Lund C, et al. Similar splice-site mutations of the ATP7A gene lead to different phenotypes: classical Menkes disease or occipital horn syndrome. Am J Hum Genet. 2000 Apr. 66(4):1211-20. [Medline].

  41. Payne AS, Gitlin JD. Functional expression of the menkes disease protein reveals common biochemical mechanisms among the copper-transporting P-type ATPases. J Biol Chem. 1998 Feb 6. 273(6):3765-70. [Medline].

  42. Petris MJ, Mercer JF. The Menkes protein (ATP7A; MNK) cycles via the plasma membrane both in basal and elevated extracellular copper using a C-terminal di-leucine endocytic signal. Hum Mol Genet. 1999 Oct. 8(11):2107-15. [Medline].

  43. Petris MJ, Mercer JF, Camakaris J. The cell biology of the Menkes disease protein. Adv Exp Med Biol. 1999. 448:53-66. [Medline].

  44. Petris MJ, Strausak D, Mercer JF. The Menkes copper transporter is required for the activation of tyrosinase. Hum Mol Genet. 2000 Nov 22. 9(19):2845-51. [Medline].

  45. Prohaska JR, Tamura T, Percy AK, Turnlund JR. In vitro copper stimulation of plasma peptidylglycine alpha-amidating monooxygenase in Menkes disease variant with occipital horns. Pediatr Res. 1997 Dec. 42(6):862-5. [Medline].

  46. Pufahl RA, Singer CP, Peariso KL, et al. Metal ion chaperone function of the soluble Cu(I) receptor Atx1. Science. 1997 Oct 31. 278(5339):853-6. [Medline].

  47. Robertson D, Goldberg MR, Onrot J, et al. Isolated failure of autonomic noradrenergic neurotransmission. Evidence for impaired beta-hydroxylation of dopamine. N Engl J Med. 1986 Jun 5. 314(23):1494-7. [Medline].

  48. Sarkar B, Lingertat-Walsh K, Clarke JT. Copper-histidine therapy for Menkes disease. J Pediatr. 1993 Nov. 123(5):828-30. [Medline].

  49. Schaefer M, Gitlin JD. Genetic disorders of membrane transport. IV. Wilson's disease and Menkes disease. Am J Physiol. 1999 Feb. 276(2 Pt 1):G311-4. [Medline].

  50. Sheela SR, Latha M, Liu P, et al. Copper-replacement treatment for symptomatic Menkes disease: ethical considerations. Clin Genet. 2005 Sep. 68(3):278-83. [Medline].

  51. Suzuki M, Gitlin JD. Intracellular localization of the Menkes and Wilson's disease proteins and their role in intracellular copper transport. Pediatr Int. 1999 Aug. 41(4):436-42. [Medline].

  52. Tumer Z, Horn N, Tonnesen T, et al. Early copper-histidine treatment for Menkes disease. Nat Genet. 1996 Jan. 12(1):11-3. [Medline].

  53. Tumer Z, Lund C, Tolshave J, et al. Identification of point mutations in 41 unrelated patients affected with Menkes disease. Am J Hum Genet. 1997 Jan. 60(1):63-71. [Medline].

  54. Tumer Z, Moller LB, Horn N. Mutation spectrum of ATP7A, the gene defective in Menkes disease. Adv Exp Med Biol. 1999. 448:83-95. [Medline].

  55. Valentine JS, Gralla EB. Delivering copper inside yeast and human cells. Science. 1997 Oct 31. 278(5339):817-8. [Medline].

  56. Voskoboinik I, Strausak D, Greenough M, et al. Functional analysis of the N-terminal CXXC metal-binding motifs in the human menkes copper-transporting P-type ATPase expressed in cultured mammalian cells. J Biol Chem. 1999 Jul 30. 274(31):22008-12. [Medline].

  57. Vulpe C, Levinson B, Whitney S, et al. Isolation of a candidate gene for Menkes disease and evidence that it encodes a copper-transporting ATPase. Nat Genet. 1993 Jan. 3(1):7-13. [Medline].

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Classic Menkes kinky hair disease in an 8-month-old male infant. Note the abnormal hair, eyelid ptosis, and jowly facial appearance.
Adolescent patient with typical occipital horn syndrome. Note elbow dislocations and genu valgum. Radiographs exhibited bilateral occipital exostoses of the skull and club-shaped distal clavicles.
Successfully treated classic Menkes kinky hair disease. Diagnosis at birth enabled copper therapy to begin when the infant was aged 8 days. The child walked independently when aged 14 months. This patient's mutation (IVS8,AS,dup5) was associated with a transcript harboring a small in-frame deletion, potentially encoding a functional copper adenosine triphosphatase (ATPase).
Menkes kinky hair disease copper adenosine triphosphatase (see text for detailed discussion).
 
 
 
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