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Inborn error of metabolism resulting from a defect in renal tubular amino acid transport leading to abnormal urinary excretion of glycine, proline, and hydroxyproline.

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Type I: Proline oxidase deficiency

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Type II: Pyrroline carboxylate dehydrogenase deficiency

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Very rare.

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Autosomal recessive; gene mapped on 22q11.2 for type I and 1p36 for type II.

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Type I is a benign disorder resulting from deficiency of proline oxidase. Type II results from a deficiency of d-pyrroline-5-carboxylate (P-5-C) dehydrogenase and may be associated with neurologic manifestations. In both conditions, plasma proline levels are increased, and three amino acids (proline, hydroxyproline, glycine) are excreted in excess in urine.

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Excess urinary proline, hydroxyproline, and glycine levels are a normal finding in the first 6 months of life. Type I is a diagnosis of exclusion: it includes all cases of hyperprolinemia not resulting from a P-5-C dehydrogenase deficiency (type II). Plasma proline level elevated but usually less than 2000 mM (normal: 100-450 mM). Urine proline also elevated. In type II, plasma proline exceeds 2000 mM. The metabolic intermediate P-5-C is 10 to 40 times above normal in the plasma and urine.

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Individuals with type I are asymptomatic. Seizures (grand mal, petit mal) and mental retardation have been associated with type II. Elevated cerebrospinal fluid (CSF) concentrations for gamma-aminobutyric acid (GABA), glutamate, and proline have been described in some patients, but their association with neurologic manifestations remains undetermined. Intestinal absorption of proline may be impaired. Heterozygotes have glycinuria only (plasma levels of amino acids are normal). Other features include dry skin, chronic inflammatory lung disease, sensorineural deafness, and ichthyosis.

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No specific precautions are required for type I. For type II, inquire about history of seizures, anticonvulsant therapy (efficacy, toxicity), and degree of mental retardation (possible need for sedative premedication).

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If a seizure disorder is associated with type II, patients receiving anticonvulsants should be maintained on their medication regimen until the time of surgery, and medications should be given parenterally postoperatively until oral intake is resumed.

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Avoid potentially epileptogenic drugs: methohexital, ketamine, enflurane, atracurium, and meperidine (Demerol) (these last two, if given in large quantity, because of their respective metabolites laudanosine and normeperidine). Consider the sedation and increased drug metabolism caused by enzymatic induction effect of phenobarbital and phenytoin; the resistance to nondepolarizing muscle relaxants with phenytoin and carbamazepine; and the potential hepatic dysfunction, thrombocytopenia, and pancreatitis with valproic acid.

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Diaminopentanuria: Inherited metabolic disorder of amino acids (defective transport system of cystine, lysine, arginine, and ornithine) resulting in precipitation of undissolved cystine in the urine (cystinuria) and causing the formation of calculi in the urinary ducts.

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Hartnup Disease: Inherited disorder of basic amino acid transport resulting in urinary loss of neutral amino acids (tryptophan, alanine, asparagine, glutamine, histidine, isoleucine, leucine, phenylalanine, serine, threonine, tyrosine, valine); affected patients present with a ...

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