Hartnup disorder

Hartnup disorder Is a rare condition caused by impaired resorption of neutral amino acids (especially tryptophan, alanine, threonine, glutamine, and histidine) In the renal tubules and malabsorption In the Intestine, resulting from mutations that lead to defective function of a neutral amino acid transporter. 

Hartnup disorder exhibits symptoms similar to pellagra (niacin deficiency), characterized by three of the "four D s" diarrhea, dermatitis (a red, scaly rash), dementia (intermittent ataxia), and death... 

Hartnup disorder is an autosomal recessive impairment of neutral amino acid transport affecting the kidney tubules and small intestine. It is believed that the defect is in a specific system responsible for neutral amino acid transport across the brush-border membrane of renal and intestinal epithelium, but the defect has not yet been characterised. 

In the disorder that was first observed in the Hailnup family and bears their name, the intestinal and renal transport defect involves the neutral amino acids (monoamine, monocarboxylic acids), including a number of the essential amino acids (isoleucine, leucine, phenylalanine, threonine, tryptophan, and valine) as well as certain nonessential amino acids (alanine, serine, and tyrosine). A reduction in the availability of these essential amino acids would be expected to cause a variety of clinical disorders. Yet children with the Hartnup disorder identified by routine newborn urine screening almost always remain clinically normal. 

Blue Indican Blue Diaper Syndrome, Hartnup disorder... 

Only tryptophanuria due to (presumed) defects in tryptophan degradation via the kynurenine pathway is considered here. Tryptophan transport defects, renal and/or intestinal (Hartnup disorder, blue-diaper syndrome) are discussed in Sect. 13.4. The symptomatology of reported cases is caused by nicotinic acid deficiency, one of the products of the said pathway. The postulated enzymatic defects have not been confirmed by in vitro investigations [7-9]. 

Fig. 12.6. Diagnostic policy for disorders of tryptophan metabolism starting points are clinical symptoms, e.g. mental retardation, ataxia, photosensitive skin rashes. " These findings support the diagnosis of Hartnup disorder...

The neutral amino acids alanine, serine, threonine, asparagine, glutamine, valine, leucine, isoleucine, phenylalanine, tyrosine, tryptophan, histidine and citrulline share a common transporter at the luminal border of the epithelial cells in the renal tubuli and the epithelial cells in the small intestine [16]. In Hartnup disorder an impairment of this transporter leads to hyperexcretion of these neutral amino acids and to intestinal malabsorption. Excretion of tryptophan metabolites kynurenine and N-methyl-nico-tinamide is reduced. Plasma concentrations of the affected amino acids may be low normal or reduced. The inheritance is autosomal recessive. The hph2-deficient mouse has been postulated as a model for Hartnup disorder [17]. Affected persons may be asymptomatic, while some demonstrate pellagra-like photodermatitis or cerebellar ataxia due to a nicotinamide deficiency and respond well to the administration of nicotinamide [16]. 

Hartnup disorder neutral amino acids Gl, renal 234500... 

Oral loading with tryptophan in Hartnup disorder will lead to increased production of indole compounds which can be analysed in the urine. 

Fig. 13.2. Diagnostic flow charts for cystinuria (a) and Hartnup disorder (b)...

Prenatal diagnosis is not recommended in cystinuria or Hartnup disorder. 

In Hartnup disorder oral nicotinamide may prevent or resolve photodermatitis. 

Levy HL. Hartnup disorder. In Scriver CR, Beaudet AL, Sly WS, Valle D. The metabolic and molecular bases of inherited disease. 2001, McGraw-Hill, New York, pp 4957-4966... 

Symula DJ, Shedlovsky A, Guillery EN, Dove WE A candidate mouse model for Hartnup disorder deficient in neutral amino acid transport. Mam Genome 1997, 8 102-107... 

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