eMedicine Specialties > Dermatology > Pediatric Diseases

Hartnup Disease: Treatment & Medication

Author: Lidija Kandolf Sekulovic, MD, PhD, Associate Professor, Head of the First Division, Department of Dermatology and Venereology, Military Medical Academy, Serbia
Coauthor(s): Djordjije Karadaglic, MD, DSc, Professor, School of Medicine, University of Podgorica, Podgorica, Montenegro; Ljubomir Stojanov, MD, PhD, Professor, University of Belgrade School of Medicine, Serbia
Contributor Information and Disclosures

Updated: Feb 6, 2009

Treatment

Medical Care

Medical care is discussed as follows:3,17,20,21,24

  • A high-protein diet can overcome the deficient transport of neutral amino acids in most patients. Poor nutrition leads to more frequent and more severe attacks of the disease, which is otherwise asymptomatic.
  • Advise all patients who are symptomatic to use physical and chemical protection from sunlight. Avoiding excessive exposure to sunlight, wearing protective clothing, and using physical and chemical sunscreens are mandatory. Recommend sunscreens with a skin protection factor of 15 or greater.
  • Advise patients to avoid other aggravating factors, such as photosensitizing drugs, as much as possible.
  • In patients with niacin deficiency and symptomatic disease, daily supplementation with nicotinic acid or nicotinamide reduces the number and the severity of attacks.
  • Neurologic and psychiatric treatment is needed in patients with severe CNS involvement.

Consultations

Helpful consultations are as follows3,21,24,26 :

  • Consult a dermatologist for diagnosis and treatment of photosensitivity and pellagralike  rash.
  • Consult an experienced neurologist for thorough follow-up monitoring and treatment of CNS involvement.
  • Consult a psychiatrist to diagnose and treat psychiatric symptoms, which may vary considerably.
  • Consult an ophthalmologist if ocular manifestations, which are rare, occur.

Diet

Advise patients who are symptomatic to consume a high-protein diet because it decreases the number of attacks.3,20,27

Activity

Advise patients to protect themselves from sunlight. Protective clothing, hats and eyewear, and physical and chemical sunscreens provide photoprotection.21

Medication

Nicotinic acid or nicotinamide (50-300 mg/d) provides relief from both the skin manifestations and the neurologic manifestations.3,17,27

Administration of tryptophan ethyl ester (a lipid-soluble tryptophan metabolite) in a child with Hartnup disease at a dose of 20 mg/kg every 6 hours resulted in normalization of serum and cerebrospinal fluid tryptophan levels.27

Vitamins

Vitamins are necessary for normal growth and development. These agents are used to replace essential vitamins not obtained in sufficient quantities in the diet or to further supplement levels.


Vitamin B-3 (Niacin, Nicotinic acid, Nicotinamide)

Nicotinamide is more commonly recommended.
Source of niacin used in tissue respiration, lipid metabolism, and glycogenolysis. Provides relief from skin and neurologic manifestations.

Adult

50-100 mg PO tid/qid; not to exceed 500 mg/d

Pediatric

50-100 mg/dose PO tid

Cutaneous vasodilation may be problematic if high dose is used with peripheral dilators (eg, nitroglycerin); decreased effect of oral hypoglycemics; may inhibit uricosuric effects of sulfinpyrazone and probenecid; decreased toxicity (flush) with aspirin; increased toxicity with lovastatin (myopathy) and possibly with other HMG-CoA reductase inhibitors; adrenergic blocking agents can have additive vasodilating effect and postural hypotension

Documented hypersensitivity; active liver disease or unexplained significant increases in AST and ALT levels; large doses of niacin, especially when administered in SR form (associated with severe hepatotoxicity, peptic ulcer, severe hypotension, arterial hemorrhaging)

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in gallbladder disease, diabetes, and in patients predisposed to gout; monitor blood glucose levels and liver function test results; may elevate uric acid levels; taking aspirin 30-60 min before first daily dose may help alleviate prostaglandin-mediated adverse effects of niacin (eg, flushing, itching); clonidine may inhibit niacin-induced flushing; some products may contain tartrazine

More on Hartnup Disease

Overview: Hartnup Disease
Differential Diagnoses & Workup: Hartnup Disease
Treatment & Medication: Hartnup Disease
Follow-up: Hartnup Disease
Multimedia: Hartnup Disease
References
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References

  1. Baron DN, Dent CE, Harris H, Hart EW, Jepson JB. Hereditary pellagra-like skin rash with temporary cerebellar ataxia, constant renal amino-aciduria, and other bizarre biochemical features. Lancet. Sep 1 1956;271(6940):421-8. [Medline].

  2. Bröer S, Cavanaugh JA, Rasko JE. Neutral amino acid transport in epithelial cells and its malfunction in Hartnup disorder. Biochem Soc Trans. Feb 2005;33:233-6. [Medline].

  3. Galadari E, Hadi S, Sabarinathan K. Hartnup disease. Int J Dermatol. Dec 1993;32(12):904. [Medline].

  4. Bröer A, Cavanaugh JA, Rasko JE, Bröer S. The molecular basis of neutral aminoacidurias. Pflugers Arch. Jan 2006;451(4):511-7. [Medline].

  5. Seow HF, Broer S, Broer A, et al. Hartnup disorder is caused by mutations in the gene encoding the neutral amino acid transporter SLC6A19. Nat Genet. Sep 2004;36(9):1003-7. [Medline].

  6. Kleta R, Romeo E, Ristic Z, et al. Mutations in SLC6A19, encoding B0AT1, cause Hartnup disorder. Nat Genet. Sep 2004;36(9):999-1002. [Medline].

  7. Broer S, Cavanaugh JA, Rasko JE. Neutral amino acid transport in epithelial cells and its malfunction in Hartnup disorder. Biochem Soc Trans. Feb 2005;33:233-6. [Medline].

  8. Nozaki J, Dakeishi M, Ohura T, et al. Homozygosity mapping to chromosome 5p15 of a gene responsible for Hartnup disorder. Biochem Biophys Res Commun. Jun 8 2001;284(2):255-60. [Medline].

  9. Bröer A, Klingel K, Kowalczuk S, Rasko JE, Cavanaugh J, Broer S. Molecular cloning of mouse amino acid transport system B0, a neutral amino acid transporter related to Hartnup disorder. J Biol Chem. Jun 4 2004;279(23):24467-76. [Medline].

  10. Symula DJ, Shedlovsky A, Dove WF. Genetic mapping of hph2, a mutation affecting amino acid transport in the mouse. Mamm Genome. Feb 1997;8(2):98-101. [Medline].

  11. Seow HF, Broer S, Broer A, et al. Hartnup disorder is caused by mutations in the gene encoding the neutral amino acid transporter SLC6A19. Nat Genet. Sep 2004;36(9):1003-7. [Medline].

  12. Azmanov DN, Kowalczuk S, Rodgers H, et al. Further evidence for allelic heterogeneity in Hartnup disorder. Hum Mutat. Oct 2008;29(10):1217-21. [Medline].

  13. Azmanov DN, Rodgers H, Auray-Blais C, et al. Persistence of the common Hartnup disease D173N allele in populations of European origin. Ann Hum Genet. Nov 2007;71:755-61. [Medline].

  14. Broer S. Apical transporters for neutral amino acids: physiology and pathophysiology. Physiology (Bethesda). Apr 2008;23:95-103. [Medline].

  15. Broer S. Apical transporters for neutral amino acids: physiology and pathophysiology. Physiology (Bethesda). Apr 2008;23:95-103. [Medline].

  16. Milovanovic DD. A clinicobiochemical study of tryptophan and other plasma and urinary amino acids in the family with Hartnup disease. Adv Exp Med Biol. 2003;527:325-35. [Medline].

  17. Schmidtke K, Endres W, Roscher A, et al. Hartnup syndrome, progressive encephalopathy and allo-albuminaemia. A clinico-pathological case study. Eur J Pediatr. Dec 1992;151(12):899-903. [Medline].

  18. Wilcken B, Yu JS, Brown DA. Natural history of Hartnup disease. Arch Dis Child. Jan 1977;52(1):38-40. [Medline].

  19. Oakley A, Wallace J. Hartnup disease presenting in an adult. Clin Exp Dermatol. Sep 1994;19(5):407-8. [Medline].

  20. Levy H. Hartnup Disorder. In: Scriver CR, Beaudet A L, Sly WS, Valle D. The metabolic and molecularbases of inherited disease. New York: McGraw-Hill; 2001:4957–4969.

  21. Stojanov LJ, Karadaglic DJ. Skin changes in children with inborn errors of amino acids metabolism. In: Karadaglic DJ, ed. Dermatology. Belgrade: Vojnoizdavacki zavod-Verzal Press; 2000:1505-12.

  22. Scriver CR, Mahon B, Levy HL, et al. The Hartnup phenotype: Mendelian transport disorder, multifactorial disease. Am J Hum Genet. May 1987;40(5):401-12. [Medline].

  23. Seyhan ME, Selimoglu MA, Ertekin V, Fidanoglu O, Altinkaynak S. Acrodermatitis enteropathica-like eruptions in a child with Hartnup disease. Pediatr Dermatol. May-Jun 2006;23(3):262-5. [Medline].

  24. Camargo SM, Bockenhauer D, Kleta R. Aminoacidurias: Clinical and molecular aspects. Kidney Int. Apr 2008;73(8):918-25. [Medline].

  25. Henderson HE, Goodman R, Schram J, Diamond E, Daneel A. Biochemical screening for inherited metabolic disorders in the mentally retarded. S Afr Med J. Nov 7 1981;60(19):731-3. [Medline].

  26. Milovanovic D, Djukic A, Stepanovic R, Pekovic D, Vranjesevic D. [Hartnup disease (report of 2 cases in one family)]. Srp Arh Celok Lek. Mar-Apr 2000;128(3-4):97-103. [Medline].

  27. Jonas AJ, Butler IJ. Circumvention of defective neutral amino acid transport in Hartnup disease using tryptophan ethyl ester. J Clin Invest. Jul 1989;84(1):200-4. [Medline].

  28. Mahon BE, Levy HL. Maternal Hartnup disorder. Am J Med Genet. Jul 1986;24(3):513-8. [Medline].

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Further Reading

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Keywords

Hartnup disease, Hartnup disorder, Hartnup aminoaciduria, Hartnup syndrome, MIM #234500, Mendelian Inheritance in Man #234500

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Contributor Information and Disclosures

Author

Lidija Kandolf Sekulovic, MD, PhD, Associate Professor, Head of the First Division, Department of Dermatology and Venereology, Military Medical Academy, Serbia
Lidija Kandolf Sekulovic, MD, PhD is a member of the following medical societies: European Academy of Dermatology and Venereology and Serbian Association of DermatoVenereologists
Disclosure: Nothing to disclose.

Coauthor(s)

Djordjije Karadaglic, MD, DSc, Professor, School of Medicine, University of Podgorica, Podgorica, Montenegro
Djordjije Karadaglic, MD, DSc is a member of the following medical societies: American Academy of Dermatology, European Academy of Dermatology and Venereology, and Serbian Association of DermatoVenereologists
Disclosure: Nothing to disclose.

Ljubomir Stojanov, MD, PhD, Professor, University of Belgrade School of Medicine, Serbia
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

David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic
David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa
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 Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University
Catherine 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.

 
 
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