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Hartnup syndrome is a rare metabolic disorder belonging to the neutral aminoacidurias and characterized by abnormal renal and gastrointestinal transport of neutral amino acids (tryptophan, alanine, asparagine, glutamine, histidine, isoleucine, leucine, phenylalanine, serine, threonine, tyrosine and valine). The estimated prevalence is approximately 1 in 24,000. Clinical symptoms usually appear in childhood (3-9 years of age), but sometimes manifest as early as 10 days after birth, or as late as early adulthood. Most subjects remain asymptomatic. Symptomatic subjects usually present with skin photosensitivity (pellagra-like skin eruption), neurological symptoms (cerebellar ataxia, spasticity, delayed motor development, trembling, headaches, and hypotonia), psychiatric symptoms (anxiety, emotional instability, delusions, and hallucinations), and aminoaciduria. Ocular manifestations may occur (double vision, nystagmus, photophobia, and strabismus). Intellectual deficit and short stature have been described in a few patients. Exacerbations are seen most frequently in the spring or early summer after sunlight exposure. Symptoms may also be triggered by fever, drugs, and emotional or physical stress. They progress over several days and last for 1-4 weeks before spontaneous remission occurs. Hartnup syndrome is an autosomal recessive disorder caused by mutations in the SLC6A19 gene (5p15.33). SLC6A19 encodes a sodium-dependent and chloride-independent neutral amino acid transporter, expressed predominately in the kidneys and intestine. Treatment includes nicotinamide supplements (40 to 200 mg per day). Neutral hyperaminoaciduria (determined by urine chromatography) is the diagnostic hallmark. Pellagra is the main differential diagnosis. Blue diaper syndrome, ataxia-telangiectasia, hydroa vacciniforme, pityriasis alba, and xeroderma pigmentosum (see these terms) should be excluded. All patients benefit from a high-protein diet, sunlight protection, and avoidance of photosensitizing drugs. Some patients may respond to a tryptophan-rich diet. Patients with severe central nervous system involvement require neurologic and psychiatric treatment.
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