Medical Care

Medical care is discussed as follows^{[3, 23, 26, 27, 34]}:

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 follows^{[3, 27, 34, 36]}:

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, 26, 37]}

Activity

Advise patients to protect themselves from sunlight. Protective clothing, hats and eyewear, and physical and chemical sunscreens provide photoprotection.^[27]

Prevention

Deterrence and prevention are as follows^{[25, 26]}:

Because sun exposure can exacerbate Hartnup disease, advise patients to protect themselves from sunlight.
Because aggravating factors, such as sulfonamides and possibly emotional stress, can exacerbate Hartnup disease, advise patients to avoid these factors.

Long-Term Monitoring

Advise patients to use protection from sunlight, to avoid other aggravating factors, to consume a high-protein diet, and to take daily supplements of nicotinic acid. In patients who are symptomatic, recommend regular follow-up examinations, depending on the severity of symptoms and the organ systems involved.

Medication

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. 1956 Sep 1. 271(6940):421-8. [QxMD MEDLINE Link].
Bröer S, Cavanaugh JA, Rasko JE. Neutral amino acid transport in epithelial cells and its malfunction in Hartnup disorder. Biochem Soc Trans. 2005 Feb. 33:233-6. [QxMD MEDLINE Link].
Galadari E, Hadi S, Sabarinathan K. Hartnup disease. Int J Dermatol. 1993 Dec. 32(12):904. [QxMD MEDLINE Link].
Bröer A, Cavanaugh JA, Rasko JE, Bröer S. The molecular basis of neutral aminoacidurias. Pflugers Arch. 2006 Jan. 451(4):511-7. [QxMD MEDLINE Link].
Hashmi MS, Gupta V. Hartnup Disease. StatPearls [Internet]. 2021 Jan. [QxMD MEDLINE Link]. [Full Text].
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. 2004 Sep. 36(9):1003-7. [QxMD MEDLINE Link].
Kleta R, Romeo E, Ristic Z, et al. Mutations in SLC6A19, encoding B0AT1, cause Hartnup disorder. Nat Genet. 2004 Sep. 36(9):999-1002. [QxMD MEDLINE Link].
Broer S, Cavanaugh JA, Rasko JE. Neutral amino acid transport in epithelial cells and its malfunction in Hartnup disorder. Biochem Soc Trans. 2005 Feb. 33:233-6. [QxMD MEDLINE Link].
Nozaki J, Dakeishi M, Ohura T, et al. Homozygosity mapping to chromosome 5p15 of a gene responsible for Hartnup disorder. Biochem Biophys Res Commun. 2001 Jun 8. 284(2):255-60. [QxMD MEDLINE Link].
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. 2004 Jun 4. 279(23):24467-76. [QxMD MEDLINE Link].
Symula DJ, Shedlovsky A, Dove WF. Genetic mapping of hph2, a mutation affecting amino acid transport in the mouse. Mamm Genome. 1997 Feb. 8(2):98-101. [QxMD MEDLINE Link].
Bröer A, Juelich T, Vanslambrouck JM, Tietze N, Solomon PS, Holst J. Impaired Nutrient Signaling and Body Weight Control in a Na+ Neutral Amino Acid Cotransporter (Slc6a19)-deficient Mouse. J Biol Chem. 2011 Jul 29. 286(30):26638-51. [QxMD MEDLINE Link].
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. 2004 Sep. 36(9):1003-7. [QxMD MEDLINE Link].
Azmanov DN, Kowalczuk S, Rodgers H, et al. Further evidence for allelic heterogeneity in Hartnup disorder. Hum Mutat. 2008 Oct. 29(10):1217-21. [QxMD MEDLINE Link].
Zheng Y, Zhou C, Huang Y, Bu D, Zhu X, Jiang W. A novel missense mutation in the SLC6A19 gene in a Chinese family with Hartnup disorder. Int J Dermatol. 2009 Apr. 48(4):388-92. [QxMD MEDLINE Link].
Cheon CK, Lee BH, Ko JM, Kim HJ, Yoo HW. Novel mutation in SLC6A19 causing late-onset seizures in Hartnup disorder. Pediatr Neurol. 2010 May. 42(5):369-71. [QxMD MEDLINE Link].
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. 2007 Nov. 71:755-61. [QxMD MEDLINE Link].
Broer S. Apical transporters for neutral amino acids: physiology and pathophysiology. Physiology (Bethesda). 2008 Apr. 23:95-103. [QxMD MEDLINE Link].
Broer S. Apical transporters for neutral amino acids: physiology and pathophysiology. Physiology (Bethesda). 2008 Apr. 23:95-103. [QxMD MEDLINE Link].
Böhmer C, Sopjani M, Klaus F, Lindner R, Laufer J, Jeyaraj S, et al. The serum and glucocorticoid inducible kinases SGK1-3 stimulate the neutral amino acid transporter SLC6A19. Cell Physiol Biochem. 2010. 25(6):723-32. [QxMD MEDLINE Link].
Nässl AM, Rubio-Aliaga I, Fenselau H, Marth MK, Kottra G, Daniel H. Amino acid absorption and homeostasis in mice lacking the intestinal peptide transporter PEPT1. Am J Physiol Gastrointest Liver Physiol. 2011 Jul. 301(1):G128-37. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Schmidtke K, Endres W, Roscher A, et al. Hartnup syndrome, progressive encephalopathy and allo-albuminaemia. A clinico-pathological case study. Eur J Pediatr. 1992 Dec. 151(12):899-903. [QxMD MEDLINE Link].
Wilcken B, Yu JS, Brown DA. Natural history of Hartnup disease. Arch Dis Child. 1977 Jan. 52(1):38-40. [QxMD MEDLINE Link].
Oakley A, Wallace J. Hartnup disease presenting in an adult. Clin Exp Dermatol. 1994 Sep. 19(5):407-8. [QxMD MEDLINE Link].
Levy H. Hartnup Disorder. Scriver CR, Beaudet A L, Sly WS, Valle D. The metabolic and molecularbases of inherited disease. New York: McGraw-Hill; 2001. 4957-4969.
Stojanov LJ, Karadaglic DJ. Skin changes in children with inborn errors of amino acids metabolism. Karadaglic DJ, ed. Dermatology. Belgrade: Vojnoizdavacki zavod-Verzal Press; 2000. 1505-12.
Mahon BE, Levy HL. Maternal Hartnup disorder. Am J Med Genet. 1986 Jul. 24(3):513-8. [QxMD MEDLINE Link].
Scriver CR, Mahon B, Levy HL, et al. The Hartnup phenotype: Mendelian transport disorder, multifactorial disease. Am J Hum Genet. 1987 May. 40(5):401-12. [QxMD MEDLINE Link].
Seyhan ME, Selimoglu MA, Ertekin V, Fidanoglu O, Altinkaynak S. Acrodermatitis enteropathica-like eruptions in a child with Hartnup disease. Pediatr Dermatol. 2006 May-Jun. 23(3):262-5. [QxMD MEDLINE Link].
Orbak Z, Ertekin V, Selimoglu A, Yilmaz N, Tan H, Konak M. Hartnup disease masked by kwashiorkor. J Health Popul Nutr. 2010 Aug. 28(4):413-5. [QxMD MEDLINE Link]. [Full Text].
Sander CS, Hertecant J, Abdulrazzaq YM, Berger TG. Severe exfoliative erythema of malnutrition in a child with coexisting coeliac and Hartnup's disease. Clin Exp Dermatol. 2009 Mar. 34(2):178-82. [QxMD MEDLINE Link].
Ciecierega T, Dweikat I, Awar M, Shahrour M, Libdeh BA, Sultan M. Severe persistent unremitting dermatitis, chronic diarrhea and hypoalbuminemia in a child; Hartnup disease in setting of celiac disease. BMC Pediatr. 2014 Dec 20. 14:311. [QxMD MEDLINE Link].
Camargo SM, Bockenhauer D, Kleta R. Aminoacidurias: Clinical and molecular aspects. Kidney Int. 2008 Apr. 73(8):918-25. [QxMD MEDLINE Link].
Henderson HE, Goodman R, Schram J, Diamond E, Daneel A. Biochemical screening for inherited metabolic disorders in the mentally retarded. S Afr Med J. 1981 Nov 7. 60(19):731-3. [QxMD MEDLINE Link].
Milovanovic D, Djukic A, Stepanovic R, Pekovic D, Vranjesevic D. [Hartnup disease (report of 2 cases in one family)]. Srp Arh Celok Lek. 2000 Mar-Apr. 128(3-4):97-103. [QxMD MEDLINE Link].
Jonas AJ, Butler IJ. Circumvention of defective neutral amino acid transport in Hartnup disease using tryptophan ethyl ester. J Clin Invest. 1989 Jul. 84(1):200-4. [QxMD MEDLINE Link].

Media Gallery

Photosensitivity with erythema, desquamation, and hypopigmentation and hyperpigmentation on the face.
Erythema and desquamation on the sun-exposed area of the right arm.

of 2

Author

Lidija Kandolf Sekulovic, MD, PhD Professor, Head of the Department of Dermatology and Venereology, Medical Faculty, Military Medical Academy, Belgrade, Serbia

Lidija Kandolf Sekulovic, MD, PhD is a member of the following medical societies: American Society of Clinical Oncology, European Academy of Dermatology and Venereology, European Society for Medical Oncology, Serbian Association of Dermatorvenerologists

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, Serbian Association of Dermatorvenerologists

Disclosure: Nothing to disclose.

Ljubomir Stojanov, MD, PhD Lecturer in Metabolism and Clinical Genetics, University of Belgrade School of Medicine, Serbia

Disclosure: Nothing to disclose.

Specialty Editor Board

David F Butler, MD Former Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Association of Military Dermatologists, Phi Beta Kappa, Texas Dermatological Society

Disclosure: Nothing to disclose.

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Professor of Pediatrics, Professor of Medicine, Rutgers New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, New York Academy of Medicine, Royal College of Physicians of Edinburgh, Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

Chief Editor

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Received income in an amount equal to or greater than $250 from: Elsevier; WebMD<br/>Served as a speaker for various universities, dermatology societies, and dermatology departments.

Acknowledgements

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.