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Aminoaciduria is caused by genetic defects in amino acid metabolism, resulting in excessive amounts of amino acids in urine. Primary and secondary aminoaciduria can be inherited or acquired through disease. Examples include phenylketonuria, homocystinuria, alkaptonuria, cystinuria, dibasic aminoaciduria, and Hartnup disease, each with their own symptoms and treatments.
Aminoaciduria is a condition in which there is an excessive amount of amino acids in the urine due to genetic defects in the pathways of amino acid metabolism. A deficiency of an enzyme that results in impaired amino acid metabolism is referred to as primary aminoaciduria. Defects in the molecular transporters responsible for the transport and absorption of an amino acid are classified as secondary aminoaciduria. Both types of aminoaciduria can be inherited, mostly in an autosomal recessive manner, but some can be acquired secondary to various diseases such as hyperparathyroidism, multiple myeloma, osteomalacia, rickets and viral hepatitis.
Some common examples of hereditary primary aminoaciduria are classical phenylketonuria, classical homocystinuria, and alkaptonuria. Classical phenylketonuria is characterized by an increased concentration of phenylalanine and its byproducts in tissues, plasma and urine due to a deficiency of phenylalanine hydroxylase. Characteristic signs of classic phenylketonuria in an untreated child include mental retardation, failure to reach early developmental milestones, microcephaly, hypopigmentation of the skin and hair, seizures, tremor, hyperactivity, and failure to thrive. Prevention of these outcomes in an infant can be accomplished by early diagnosis and initiation of dietary treatment before 3 weeks of age.
Classical homocystinuria is characterized by an increased concentration of homocysteine and methionine and a decreased concentration of cysteine in plasma and urine. This results from reduced cystathionine beta-synthetase activity. Affected individuals present with the optical lens displacement known as ectopia lentis, mental retardation, skeletal abnormalities, osteoporosis, and premature arterial disease. Treatment is dietary restriction of protein and methionine and supplementation with vitamins B6, B12, and folate.
Alkaptonuria is characterized by an increased concentration of homogentisic acid in urine and connective tissues due to a deficiency of homogentisic acid oxidase. Affected individuals are usually asymptomatic until their 30s or 40s. The three characteristic symptoms of alkaptonuria are the presence of dark urine, arthritis of the large joints and dark ears, and other cartilaginous tissue and collagen. Prevention of long-term complications can be done through restriction of the protein diet, especially in phenylalanine and tyrosine, together with the use of the drug nitisone.
Some common examples of hereditary secondary aminoaciduria are cystinuria, dibasic aminoaciduria, and Hartnup disease. Cystinuria, due to a transporter defect in the kidney and small intestine, is characterized by impaired reabsorption and excessive excretion of the dibasic amino acids cystine, arginine, lysine, and ornithine in the urine. The poor solubility of cystine predisposes to the formation of renal, ureteral and bladder stones, which can lead to renal failure. The goal of treatment is to prevent the formation of stones from permanent alkaline diuresis. Depending on the presentation of affected individuals, the use of penicillamine and thiopronin, shock wave lithotripsy, ureteroscopy, percutaneous nephrolithotomy, or open urologic surgery may be considered.
Dibasic aminoaciduria is characterized by a selective defect in the reabsorption of arginine, lysine and ornithine. Affected individuals may have an enlarged liver, protein intolerance, hyperammonemia, impaired kidney function, severe osteoporosis, or structural changes in the lungs. Treatment consists of dietary protein restriction and citrulline supplementation.
Hartnup disease is characterized by variable neurologic manifestations, such as cerebellar ataxia or delirium, accompanied by pellagra-like skin lesions. This is due to a defect in a transporter located in the kidneys and intestines, resulting in increased urinary excretion of alanine, threonine, leucine, isoleucine, asparagine, glutamine, histidine, serine, tyrosine, valine, tryptophan and phenylalanine. Treatment includes a high protein diet and nicotinamide supplementation.
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