Hartnup Disease Clinical Presentation

  • Author: Lidija Kandolf Sekulovic, MD, PhD; Chief Editor: William D James, MD   more...
 
Updated: Aug 16, 2011
 

History

Hartnup disease is manifested by a wide clinical spectrum and phenotypic heterogeneity (see Physical for a complete discussion of the clinical signs).[22, 23, 27] Note the following:

  • Most children with the Hartnup defect remain asymptomatic.
  • In Australia, an 8-year follow-up study of 12 patients found only 2 clinical episodes that may be ascribed to Hartnup disease; mental development of all of the children was normal. In the United States, a full-blown picture of the disorder is rarely seen, probably because the diet of US residents is adequate.[23]
  • Patients who are symptomatic present with episodic deterioration of neurologic and dermatologic manifestations. Symptoms progress over several days and last for 1-4 weeks before spontaneous remission occurs.
  • Cutaneous signs usually precede the neurologic manifestations, but in rare patients, neurologic manifestations can precede skin changes.[24, 15]
  • Psychiatric symptoms (eg, anxiety, emotional instability, mood changes) are common in patients who are symptomatic. Psychotic episodes and delirium are rarely seen.
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Physical

Skin findings are as follows[1, 23, 26] :

  • Photosensitivity occurs (see the image below).The skin reddens after exposure to sunlight (see the image below). Further exposures lead to the development of dry, scaly, well-marginated eruptions, sometimes resembling chronic eczema. This eruption preferentially affects the forehead, the cheeks, the periorbital regions, the dorsal surfaces of the hands, and other light-exposed areas. Photosensitivity with erythema, desquamation, and Photosensitivity with erythema, desquamation, and hypopigmentation and hyperpigmentation on the face. Erythema and desquamation on the sun-exposed area Erythema and desquamation on the sun-exposed area of the right arm.
  • Lesions on the face may resemble the malar rash of lupus erythematosus.
  • A vesiculobullous eruption with exudation may occur.
  • Skin changes leave long-lasting hypopigmentation and/or hyperpigmentation, which are intensified with further sunlight exposure.
  • One case with widespread cutaneous eruption resembling acrodermatitis enteropathica was described,[28] as well as a patient with manifestations of kwashiorkor and acrodermatitis enteropathica but with normal zinc levels, which led to the search for other metabolic disorders, and Hartnup disorder was confirmed.[29]
  • In one patient with concurrent coeliac disease and Hartnup disease, severe exfoliative erythroderma of malnutrition developed; it resolved after a high-protein and gluten-free diet was instituted.[30]

Central nervous system findings are as follows[31] :

  • Mental development is normal in most patients, but mental retardation (intelligence quotient of 50-70) is described in a few patients. Of 1087 patients screened for the detection of inherited metabolic diseases from the Alexandra Institute for persons with mental retardation in Cape Town, Hartnup disease was found in only 1 patient.[32]
  • Neurologic symptoms may vary and are fully reversible. Intermittent cerebellar ataxia, a wide-based gait, spasticity, delayed motor development, and tremulousness are the most frequent findings. Headaches and hypotonia may also occur.[23, 27, 33] . Late-onset seizures and adult-onset Hartnup disease with neurologic manifestations as the first signs have been described, with pellagralike skin lesions developing after the neurologic symptoms.[24, 15]
  • Ocular manifestations include double vision, nystagmus, photophobia, and strabismus.[27]

Other findings may include the following:

  • Gingivitis, stomatitis, and glossitis suggest niacin deficiency.[3, 31]
  • Diarrhea occasionally precedes or follows attacks of the disease.[3, 31]
  • Short stature has been described. Wilcken et al found that of 14 patients with Hartnup disorder who were observed for 8 years, 10 had height percentiles less than the midparent height percentiles, while 4 had percentiles equal to or above the midparent percentiles.[23]
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Causes

Exacerbations are seen most frequently in the spring or early summer after exposure to sunlight. The attacks may be provoked by a febrile illness, poor nutrition, sulfonamides, and possibly emotional stress and increased physical activity.[24, 25]

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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  Lecturer in Metabolism and Clinical Genetics, University of Belgrade School of Medicine, Serbia

Disclosure: Nothing to disclose.

Specialty Editor Board

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.

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.

Robert A Schwartz, MD, MPH  Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, University of Medicine and Dentistry of New Jersey-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.

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

William D James, MD  Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System

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

Disclosure: Elsevier Royalty Other

References

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