Disorder of neutral amino acid transport

Disorder of neutral amino acid transport (Orphanet code 308451) is a broad category encompassing rare inherited metabolic conditions in which the body's ability to transport neutral amino acids across cell membranes is impaired. The best-known condition in this group is Hartnup disease (also called Hartnup disorder), which results from defective transport of neutral amino acids (such as tryptophan, alanine, serine, threonine, valine, leucine, isoleucine, and phenylalanine) in the intestinal epithelium and renal proximal tubules. This leads to excessive urinary excretion of these amino acids (aminoaciduria) and impaired intestinal absorption. Because tryptophan is a precursor to niacin (vitamin B3), affected individuals may develop pellagra-like symptoms including a photosensitive skin rash, cerebellar ataxia, and neuropsychiatric manifestations such as emotional instability, cognitive difficulties, and psychotic episodes. Other body systems that may be affected include the gastrointestinal tract, with intermittent diarrhea reported in some patients. The clinical presentation is highly variable. Many individuals identified through newborn screening remain asymptomatic throughout life, while others develop episodic symptoms triggered by poor nutrition, illness, stress, or sun exposure. Symptoms typically first appear in childhood but can manifest at any age. The severity of clinical features often correlates with dietary niacin intake and overall nutritional status. Treatment is primarily supportive and nutritional. Oral nicotinamide (niacinamide) supplementation is the mainstay of therapy and can effectively prevent or ameliorate symptoms. A high-protein diet is recommended to compensate for impaired amino acid absorption. Sun protection is advised to prevent photosensitive skin reactions. With appropriate management, the prognosis is generally favorable, and many patients experience improvement or resolution of symptoms with age. Genetic counseling is recommended for affected families.

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