A 28- year-old man complains of a rash on his sun- exposed skin, diarrhea and loss of balance. His urinalysis results are significant for an increase in neutral amino acids. The patient is diagnosed with Hartnup’s disease that occurs due to a defective transport of neutral amino acids in the kidney. Apart from tryptophan which of the following amino acids would have been found in urine?
D. Phenyl alanine
E. Glutamic acid
The right option is D- Phenyl alanine. Hartnup disease is an autosomal recessive disorder caused by impaired neutral (i.e., mono amino mono carboxylic) amino acid transport in the apical brush border membrane of the small intestine and the proximal tubule of the kidney. Patients present with pellagra like skin eruptions, cerebellar ataxia, and gross aminoaciduria.
The disorder was first observed in the Hartnup family of London; 4 of the 8 family members presented with aminoaciduria, a rash resembling pellagra, and cerebellar ataxia. A person with Hartnup disease cannot absorb amino acids properly from the intestine and from tubules in the kidneys. Excessive amounts of amino acids, such as Tryptophan, are excreted in the urine. The body is thus left with inadequate amounts of amino acids, which are the building blocks of proteins.
With too little Tryptophan in the blood, the body is unable to make a sufficient amount of the B-complex vitamin niacinamide, particularly under stress when more vitamins are needed. As a result, tryptophan and niacin deficiencies generate similar symptoms.
Amino acids are retained within the intestinal lumen, where they are converted by bacteria to indolic compounds that can be toxic to the CNS. Tubular renal transport is also defective, contributing to gross aminoaciduria. Neutral amino acids are also found in the feces.
Hartnup disease manifest during infancy with variable clinical presentation: failure to thrive, photosensitivity, intermittent ataxia, nystagmus and tremor. Symptoms may be triggered by sunlight, fever, drugs, or emotional or physical stress. A period of poor nutrition nearly always precedes an attack. Most symptoms occur sporadically and are caused by a deficiency of niacinamide.
A rash develops on parts of the body exposed to the sun. Mental retardation, short stature, headaches, unsteady gait, and collapsing or fainting are common. Psychiatric problems (such as anxiety, rapid mood changes, delusions, and hallucinations) may also result. Cutaneous signs usually precede the neurological manifestations.
Urine Analysis reveals the presence of neutral amino acids, tryptophan, Indole derivatives and tryptophan degradation products.
A high-protein diet can overcome the deficient transport of neutral amino acids in most patients.
Since the defect lies in the absorption of neutral amino acids and in the given list it is only phenyl alanine which is neutral, rest all are charged amino acids at physiological pH, thus phenyl alanine could also be excreted excessively in urine besides Tryptophan.
Lysine, arginine and histidine are basic amino acids whereas Glutamic acid is an acidic amino acid , these amino acids have different transporters for their absorption.
The absorption of amino acids takes place by active transport (same as that of glucose). Natural L-amino acids are actively transported. D- Amino acids are absorbed by simple diffusion. Vitamin B6 is involved in the active transfer of amino acids.
It is an energy requiring process; ATP is required as a source of energy. A carrier protein is also required which may be Na+ dependent or independent.
Different carrier proteins are there specific for different amino acids.
Five types of transporters have been reported, for neutral, acidic, basic, imino acids and Beta amino acids (β- Alanine). In Hartnup disease, it is the neutral amino acid transporter that is defective (Figure)
Figure- Absorption of amino acids is an active process mediated by specific transporters
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