Inborn error of metabolism resulting from a defect in
renal tubular amino acid transport leading to abnormal urinary excretion of
glycine, proline, and hydroxyproline.
Type I: Proline oxidase deficiency
Type II: Pyrroline carboxylate dehydrogenase deficiency
Autosomal recessive; gene mapped on 22q11.2
for type I and 1p36 for type II.
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.
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
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.
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).
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.
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.
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.
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 ...