Hartnup Disease

Inherited metabolic disorder characterized by a pellagra-like skin eruption, cerebellar ataxia, and gross aminoaciduria. Most children are asymptomatic.

H Disease; Hart Syndrome; Hartnup Disorder or Syndrome; Pellagra-Cerebellar Ataxia-Renal Aminoaciduria Syndrome; Tryptophan Pyrrolase Deficiency.

Metabolic disorder of amino acids named after the first family in which the disorder was found (Hartnup family of London).

Approximately 1:15,000 live births in the United States (similar to phenylketonuria); 1:18,000-42,000 live births in the rest of the world. No racial or sex predilection.

Autosomal recessive (probably a monogenic defect that interacts with polygenic and environmental factors, giving a wide clinical spectrum). Gene located on 5p15.

Defect of transport of neutral alpha-amino acids (mainly tryptophan) across the intestinal mucosa and renal tubules as a result of defective tryptophan pyrrolase. Retained amino acids are converted by intestinal bacteria to indolic compounds, which have a cerebral toxicity.

Amino aciduria limited to neutral alpha-amino acids, indicanuria (excludes nutritional pellagra). Oral tryptophan load causes urinary excretion of 5-hydroxyindoleacetic acid. Jejunal and skin biopsies may be required in selected patients.

Routine neonatal urine screening has indicated that many individuals with this defect are asymptomatic. Affected patients develop a photosensitive skin rash, usually beginning in children 3 to 9 years old (but may present during the neonatal period). Typically, after sunlight exposure, the skin reddens. A dry, scaly, well-marginated eruption may develop on the face and other light-exposed areas. With time, pigmentation changes may become definitive. More rarely, episodes of cerebellar ataxia, emotional lability, encephalopathy, and ocular manifestations occur. The episodes are reversible with treatment, which consists of nicotinic acid supplementation with a high-protein diet (in addition to use of creams for protection from sunlight). Exacerbations occur most often in spring or early summer after exposure to sunlight. They may be favored by febrile illness, poor nutrition, treatment with sulfonamides, and emotional stress.

Assess extent of skin and neurologic involvement.

No particular difficulties with anesthesia have been reported. Periods of induced stress may be associated with acute exacerbation in some patients.

Administration of sulfonamides should be avoided because they may exacerbate the disease.

Hydroa Vacciniforme (Bazin Hydroa Vacciniforme): Rare, chronic photodermatosis of unknown etiology. Recurrent vesicles on sun-exposed skin that heal with vacciniform or varioliform scarring. The histopathology is distinctive with intraepidermal reticular degeneration and cellular necrosis. May be accompanied by mild keratoconjuctivitis and photophobia.

Pityriasis Alba: Common hypopigmented dermatitis that occurs primarily in school-age children (3-16 years of age). Occasionally occurs in adults. In the United States, the incidence is believed to be 33% of school-age children; the condition is more obvious during sun exposure. Approximately 40% of Egyptian children are affected. Nonspecific dermatitis of unknown etiology.

Xeroderma Pigmentosum (XP): Syndrome characterized by a defect in ultraviolet radiation-induced DNA repair mechanisms. It is characterized by severe sensitivity to all sources of UV radiation (especially sunlight). Xeroderma pigmentosum is categorized into seven complementation groups according to the capacity of the body to repair DNA. It is a life-threatening disorder. DNA damage is cumulative and irreversible. Often lethal in infancy or childhood.