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ABSTRACT

  • Membrane transport of cationic amino acids lysine, arginine, and ornithine is abnormal in four disease entities: classic cystinuria; lysinuric protein intolerance (hyperdibasic aminoaciduria type 2, or familial protein intolerance); hyperdibasic aminoaciduria type 1; and isolated lysinuria (lysine malabsorption syndrome). Cystinuria, the most common of these, is dealt with in Chap. 233. About 100 patients with lysinuric protein intolerance (LPI) have been reported or are known to me. Almost half of them are from Finland, where the prevalence of this autosomal recessive disease is 1 in 60,000. Autosomal dominant hyperdibasic aminoaciduria type 1 has been described in 13 of 33 members in a French Canadian pedigree, and isolated lysinuria has been described in one Japanese patient.

    Arginine and ornithine are intermediates in the urea cycle; lysine is an essential amino acid. In lysinuric protein intolerance (LPI) (MIM 222700), urinary excretion and clearance of all cationic amino acids, especially of lysine, are increased, and these amino acids are poorly absorbed from the intestine. Their plasma concentrations are low, and their body pools become depleted. The patients have periods of hyperammonemia caused by “functional” deficiency of ornithine, which provides the carbon skeleton of the urea cycle. Consequently, nausea and vomiting occur, and aversion to protein-rich food develops. The patients fail to thrive, and symptoms of protein malnutrition are further aggravated by lysine deficiency.

  • Patients with LPI are usually symptom-free when breast-fed but have vomiting and diarrhea after weaning. The appetite is poor, they fail to thrive, and if force-fed high-protein milk or formulas, they may go into coma. After infancy, they reject high-protein foods, grow poorly, and have enlarged liver and spleen, muscle hypotonia, and sparse hair. Osteoporosis is prominent, and fractures are not uncommon; bone age is delayed. The mental prognosis varies from normal development to moderate retardation; most patients are normal. Four patients have had psychotic periods. The final height in treated patients has been slightly subnormal or low-normal. Pregnancies are risky: Profound anemia develops, platelet count decreases, and severe hemorrhages during labor and a toxemic crisis have occurred, but the offspring are normal if not damaged by delivery-related complications. Acute exacerbations of hyperammonemia have not been a frequent problem in treated patients, but may have been the cause of the sudden death in one adult male after moderate alcohol ingestion. About two thirds of the patients have interstitial changes in chest radiographs. Some patients have developed acute or chronic respiratory insufficiency, which in a few has led to fatal pulmonary alveolar proteinosis and to multiple organ dysfunction syndrome. Patients present with fatigue, cough, dyspnea during exercise, fever, and, rarely, hemoptysis, and may also show signs of nephritis and renal insufficiency. One adult patient with pulmonary symptoms has been treated with high-dose prednisolone and is in remission over 6 years after the occurrence of the symptoms. In another patient, bronchoalveolar lavages have produced immediate relief during several subacute exacerbations.

  • In LPI, the concentrations of the cationic amino acids in plasma are subnormal ...

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