eMedicine Specialties > Dermatology > Pediatric Diseases

Menkes Kinky Hair Disease: Treatment & Medication

Author: Suguru Imaeda, MD, Chief of Dermatology, Yale University Health Services; Chief of Dermatology, West Haven Veterans Affairs Medical Center; Assistant Professor, Department of Dermatology, Yale University School of Medicine
Contributor Information and Disclosures

Updated: Nov 13, 2009

Treatment

Medical Care

Medical care is mainly supportive for Menkes kinky hair syndrome patients.

  • The administration of parenteral copper is ineffective at influencing the clinical course and fatal outcome. However, early parenteral administration has been demonstrated to prevent some neurological disturbances.17
    • Some patients who receive copper-histidinate supplementation have serum copper and ceruloplasmin levels in the reference range.18,19
    • Despite these levels, their clinical features are unaltered.
  • Intracerebroventricular copper histidine injection in a rat model of Menkes disease restored the brain copper concentration, suggesting the possibility of this method as a novel treatment approach in Menkes disease infants with severe mutations.20
  • The use of antiseizure medications may be indicated.
  • One clinical trial measured plasma dopamine, norepinephrine, dihydroxyphenylacetic acid, and dihydroxyphenylglycol levels in 81 infants at risk. In 12 newborns who met the eligibility criteria, copper-replacement therapy was begun within 22 days after birth. Survival and neurodevelopment was tracked longitudinally for 1.5-8 years; survival at a median follow-up of 4.6 years was 92%, compared with 13% at a median follow-up of 1.8 years for a historical control group of 15 late-diagnosis and late-treatment patients. Two of the 12 patients had normal neurodevelopment and brain myelination.21

Surgical Care

Please see Special Concerns for problems associated with airway management.

Consultations

  • Consult a neurologist for seizure management.
  • Consult a geneticist for counseling and prenatal testing.
    • Prenatal diagnosis by means of DNA mutational analysis (preferred method) may be performed.
    • Copper-64 incorporation by chorionic villus cells or amniotic fluid cells may be observed.
  • Carrier status can be determined by observing copper-64 uptake in cultured fibroblasts or by means of DNA mutational analysis, which is the preferred method. Denaturing high-performance liquid chromatography has been used effectively for mutation screening in patients with Menkes disease.22

Medication

Antiseizure medications can be helpful for supportive care in Menkes kinky hair syndrome. No other therapy is available.

Anticonvulsants

These agents prevent seizure recurrence and terminate clinical and electrical seizure activity.


Phenytoin (Dilantin)

May act in motor cortex where may inhibit spread of seizure activity. Activity of brainstem centers responsible for tonic phase of grand mal seizures also may be inhibited. Individualize dosing; if dose cannot be divided equally, larger dose should be taken before retiring for the evening.

Adult

If rapid achievement of steady-state serum levels needed (eg, in status epilepticus), administer loading dose of 15-20 mg/kg PO/IV once or divided, followed by 100 mg q6-8h
Initial dose: 100 mg (125-mg susp) PO/IV tid
Maintenance dose: 300-400 mg/d PO/IV divided tid or qd/bid if using extended release; gradual increase by 100 mg q2-4wk to 600 mg/d (625 mg/d susp) may be necessary; infusion rate not to exceed 50 mg/min (25 mg/min in geriatric patients with heart disease) to avoid hypotension and arrhythmias; total dose not to exceed 1500 mg/24h

Pediatric

<6 years: 15-20 mg/kg PO/IV loading dose once or in divided doses; rate not to exceed 1-3 mg/kg/min; dose not to exceed 20 mg/kg/d; follow with initial 5 mg/kg/d maintenance dose (range, 4-8 mg/kg/d) PO/IV divided bid/tid
>6 years: May require minimum adult dose (300 mg/d); not to exceed 300 mg/d

Amiodarone, benzodiazepines, chloramphenicol, cimetidine, fluconazole, isoniazid, metronidazole, miconazole, phenylbutazone, succinimide, sulfonamides, omeprazole, phenacemide, disulfiram, ethanol (acute ingestion), trimethoprim, and valproic acid may increase toxicity; effects may decrease when taken concurrently with barbiturates, diazoxide, ethanol (chronic ingestion), rifampin, antacids, charcoal, carbamazepine, theophylline, and sucralfate
May decrease effects of acetaminophen, corticosteroids, dicumarol, disopyramide, doxycycline, estrogens, haloperidol, amiodarone, carbamazepine, cardiac glycosides, quinidine, theophylline, methadone, metyrapone, mexiletine, oral contraceptives, and valproic acid; coadministration of acetazolamide and phenytoin may produce osteomalacia if these medications are used on a long-term basis; TCAs may lower seizure threshold in epileptic patients stabilized on anticonvulsants; concurrent use of phenytoin and clofazimine may result in reduced phenytoin efficacy; diltiazem is documented to result in clinically significant elevations in phenytoin serum levels associated with signs and symptoms of phenytoin toxicity; concurrent use of folic acid and phenytoin has resulted in increased seizure frequency and decreased phenytoin levels in some patients; significantly increased phenytoin levels reported with concurrent use of phenytoin and nafimidone in epileptic patients; concurrent administration of phenytoin and viloxazine may produce elevated phenytoin serum concentrations

Documented hypersensitivity to drug or related agents, sinoatrial block, second- and third-degree AV block, sinus bradycardia, or Adams-Stokes syndrome

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Perform CBC counts and urinalyses when therapy is begun and at monthly intervals for several months thereafter to monitor for blood dyscrasias; discontinue if rash appears, and do not resume if rash is exfoliative, bullous, or purpuric; rapid IV infusion may result in death from cardiac arrest marked by QRS widening; caution in acute intermittent porphyria and diabetes (may elevate blood glucose level); discontinue if hepatic dysfunction occurs; abrupt withdrawal may precipitate status epilepticus; nephrotoxicity that includes interstitial nephritis, nephrotic syndrome and renal failure reported with therapeutic phenytoin use; coarsening of facial features, enlargement of lips, and hypertrichosis has occurred with phenytoin therapy; phenytoin interferes with vitamin D metabolism and may cause osteomalacia; long-term phenytoin therapy is associated with symptomatic and asymptomatic peripheral neuropathy and neuromuscular disorders


Carbamazepine (Tegretol)

May reduce polysynaptic responses and block posttetanic potentiation.

Adult

200 mg PO bid (or 100 mg susp PO qid); increase by no more than 200 mg/d tid/qid (bid with extended release) at weekly intervals until best response obtained; not to exceed 1200 mg/d, or in rare instances, 1600 mg/d

Pediatric

<6 years: 10-20 mg/kg/d PO bid/tid (qid with susp); increase weekly to tid/qid achieve optimal clinical response; not to exceed 35 mg/kg/d
6-12 years: 100 mg PO bid (50 mg susp qid); increase by 100 mg/d PO divided tid/qid (bid with extended release) weekly until best response; not to exceed 1000 mg/d
>12 years: Administer as in adults; not to exceed 1000 mg/d in children 12-15 y or 1200 mg/d if >15 y

Serum levels may increase significantly within 30 d of danazol coadministration (avoid whenever possible); do not coadminister with MAOIs; cimetidine may increase toxicity, especially if taken in first 4 wk of therapy; may decrease primidone and phenobarbital levels (coadministration may increase carbamazepine levels); coadministration with erythromycin may increase serum levels; doses of carbamazepine may need to be increased in patients receiving antineoplastic therapy with doxorubicin or cisplatin

Documented hypersensitivity to drug or related products; history of bone marrow depression, MAOIs within last 14 d

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Not for use to relieve minor aches or pains; caution with increased intraocular pressure; obtain CBC counts and serum iron baseline prior to treatment, during first 2 mo, and yearly or every other year thereafter; can cause drowsiness, dizziness, and blurred vision; caution while driving or performing other tasks requiring alertness; adverse effects include acute intermittent porphyria, acute renal failure, agranulocytosis, aplastic anemia, AV block, bone marrow depression, cardiac dysrhythmia, congestive heart failure, drug-induced eosinophilia, hepatitis, leukocytosis, leukopenia, nephrotoxicity, systemic lupus erythematosus, thrombocytopenia, and toxic epidermal necrolysis
Caution in breastfeeding, elderly patients, history of adverse hematological reaction to any drug, history of cardiac damage, increased intraocular pressure, kidney dysfunction, liver dysfunction, and history of atypical absence seizures; MAOIs must be discontinued for a minimum of 14 d before starting carbamazepine; patients with underlying mental illness may experience activation of latent psychosis or agitation; do not discontinue abruptly; patients receiving carbamazepine therapy should avoid grapefruit juice consumption

More on Menkes Kinky Hair Disease

Overview: Menkes Kinky Hair Disease
Differential Diagnoses & Workup: Menkes Kinky Hair Disease
Treatment & Medication: Menkes Kinky Hair Disease
Follow-up: Menkes Kinky Hair Disease
References
[ CLOSE WINDOW ]

References

  1. Menkes JH, Alter M, Steigleder GK, Weakley DR, Sung JH. A sex-linked recessive disorder with retardation of growth, peculiar hair, and focal cerebral and cerebellar degeneration. Pediatrics. May 1962;29:764-79. [Medline].

  2. Danks DM, Campbell PE, Stevens BJ, Mayne V, Cartwright E. Menkes's kinky hair syndrome. An inherited defect in copper absorption with widespread effects. Pediatrics. Aug 1972;50(2):188-201. [Medline].

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

  4. Price DJ, Ravindranath T, Kaler SG. Internal jugular phlebectasia in Menkes disease. Int J Pediatr Otorhinolaryngol. Jul 2007;71(7):1145-8. [Medline].

  5. Oshio T, Hino M, Kirino A, Matsumura C, Fukuda K. Urologic abnormalities in Menkes' kinky hair disease: report of three cases. J Pediatr Surg. May 1997;32(5):782-4. [Medline].

  6. Balestracci A, Caletti MG, Missoni M. A case of Menkes' disease with nephrocalcinosis and chronic renal failure. Pediatr Nephrol. Jun 2009;24(6):1255-6. [Medline].

  7. Spitz JL. Genodermatoses. Vol 1. Baltimore, Md: Williams & Wilkins; 1996:230-1.

  8. Harris ED, Qian Y, Reddy MC. Genes regulating copper metabolism. Mol Cell Biochem. Nov 1998;188(1-2):57-62. [Medline].

  9. Liu PC, Chen YW, Centeno JA, Quezado M, Lem K, Kaler SG. Downregulation of myelination, energy, and translational genes in Menkes disease brain. Mol Genet Metab. Aug 2005;85(4):291-300. [Medline].

  10. La Fontaine S, Mercer JF. Trafficking of the copper-ATPases, ATP7A and ATP7B: role in copper homeostasis. Arch Biochem Biophys. Jul 15 2007;463(2):149-67. [Medline].

  11. Madsen E, Gitlin JD. Copper and iron disorders of the brain. Annu Rev Neurosci. 2007;30:317-37. [Medline].

  12. Madsen E, Gitlin JD. Copper deficiency. Curr Opin Gastroenterol. Mar 2007;23(2):187-92. [Medline].

  13. Donsante A, Tang J, Godwin SC, et al. Differences in ATP7A gene expression underlie intrafamilial variability in Menkes disease/occipital horn syndrome. J Med Genet. Aug 2007;44(8):492-7. [Medline].

  14. Bertini I, Rosato A. Menkes disease. Cell Mol Life Sci. Jan 2008;65(1):89-91. [Medline].

  15. Matsuo M, Tasaki R, Kodama H, Hamasaki Y. Screening for Menkes disease using the urine HVA/VMA ratio. J Inherit Metab Dis. 2005;28(1):89-93. [Medline].

  16. Ozawa H, Kodama H, Kawaguchi H, Mochizuki T, Kobayashi M, Igarashi T. Renal function in patients with Menkes disease. Eur J Pediatr. Jan 2003;162(1):51-2. [Medline].

  17. Sheela SR, Latha M, Liu P, Lem K, Kaler SG. Copper-replacement treatment for symptomatic Menkes disease: ethical considerations. Clin Genet. Sep 2005;68(3):278-83. [Medline].

  18. Hoppe-Tichy T, Nguyen TH, Hentze BW, Lorke M. [Manufacturing and stability of copper-histidine solution for treatment of Menkes' Kinky Hair Syndrome]. Pharmazie. Mar 2005;60(3):205-7. [Medline].

  19. Munakata M, Sakamoto O, Kitamura T, et al. The effects of copper-histidine therapy on brain metabolism in a patient with Menkes disease: a proton magnetic resonance spectroscopic study. Brain Dev. Jun 2005;27(4):297-300. [Medline].

  20. Lem KE, Brinster LR, Tjurmina O, et al. Safety of intracerebroventricular copper histidine in adult rats. Mol Genet Metab. May 2007;91(1):30-6. [Medline].

  21. Kaler SG, Holmes CS, Goldstein DS, et al. Neonatal diagnosis and treatment of Menkes disease. N Engl J Med. Feb 7 2008;358(6):605-14. [Medline].

  22. Watanabe A, Shimizu N. Identification of three novel mutations in Japanese patients with Menkes disease and mutation screening by denaturing high performance liquid chromatography. Pediatr Int. Feb 2005;47(1):1-6. [Medline].

  23. Kazim R, Weisberg R, Sun LS. Upper airway obstruction and Menkes syndrome. Anesth Analg. Oct 1993;77(4):856-7. [Medline].

  24. Tobias JD. Anaesthetic considerations in the child with Menkes' syndrome. Can J Anaesth. Sep 1992;39(7):712-5. [Medline].

  25. Sugimoto M, Shindo K, Shingu K, Mori K. [Anesthetic management of an infant with Menkes disease]. Masui. Sep 1993;42(9):1351-4. [Medline].

  26. Brownstein JN, Primosch RE. Oral manifestations of Menkes' kinky hair syndrome. J Clin Pediatr Dent. Summer 2001;25(4):317-21. [Medline].

  27. Freedberg IM, Eisen AZ, Wolff K. Fitzpatrick's Dermatology in General Medicine. New York, NY: McGraw-Hill; 1999:732, 2141.

  28. Hart DB. Menkes' syndrome: an updated review. J Am Acad Dermatol. Jul 1983;9(1):145-52. [Medline].

  29. Hurwitz S. Clinical Pediatric Dermatology: A Textbook of Skin Disorders of Childhood and Adolescence. 2nd ed. Philadelphia, Pa: WB Saunders; 1993:498-9.

  30. Jayawant S, Halpin S, Wallace S. Menkes kinky hair disease: an unusual case. Eur J Paediatr Neurol. 2000;4(3):131-4. [Medline].

  31. Martins C, Goncalves C, Moreno A, Goncalves O, Baptista AP, Bairos V. Menkes' kinky hair syndrome: ultrastructural cutaneous alterations of the elastic fibers. Pediatr Dermatol. Sep-Oct 1997;14(5):347-50. [Medline].

  32. Sybert VP. Genetic Skin Disorders. ed. New York, NY: Oxford University Press; 1997:195-8.

  33. Tumer Z, Horn N. Menkes disease: underlying genetic defect and new diagnostic possibilities. J Inherit Metab Dis. Aug 1998;21(5):604-12. [Medline].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

Menkes kinky hair disease, Menkes kinky hair syndrome, steely hair syndrome, trichopoliodystrophy, copper metabolism, copper deficiency, pili torti, hair-shaft abnormality

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Suguru Imaeda, MD, Chief of Dermatology, Yale University Health Services; Chief of Dermatology, West Haven Veterans Affairs Medical Center; Assistant Professor, Department of Dermatology, Yale University School of Medicine
Suguru Imaeda, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, Connecticut State Medical Society, Sigma Xi, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

Medical Editor

Mark A Crowe, MD, Assistant Clinical Instructor, Department of Medicine, Division of Dermatology, University of Washington School of Medicine
Mark A Crowe, MD is a member of the following medical societies: American Academy of Dermatology and North American Clinical Dermatologic Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Michael J Wells, MD, Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center
Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi
Disclosure: Nothing to disclose.

CME Editor

Catherine M Quirk, MD, Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania
Catherine M Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.