Genetic disorder with increased renal clearance of
cystine, lysine, arginine, and ornithine caused by a dysfunction of the
reabsorptive capacity of the renal tubules. In addition, defective
intestinal absorption results in increased degradation of these amino acids
by bacteria in the intestine.
Fewer than five patients
reported in the literature. Genetic inheritance is unknown.
Increased renal clearance of cystine and the
dibasic amino acids lysine, arginine, and ornithine, in the presence of
normal or low plasma levels of these compounds, is secondary to dysfunction
of the reabsorptive capacity of the renal tubule. Defective intestinal
absorption of cystine, lysine, arginine, and ornithine results in increased
degradation of these amino acids by bacteria in the intestinal tract.
Alternate intestinal transport routes may protect cystinuric patients from
amino acid malnutrition because they respond to a large oral dose of lysine
with a normal increase of its plasma concentration. Although cystinuria may
be associated with CNS abnormalities, the precise mechanism of action
remains to be determined. In cystine-lysinuria, production of cadaverine
(1,5-diaminopentane) and putrescine by bacterial conversion of lysine and
ornithine may play a role in the pathophysiology.
Diagnosis made by the clinical course, microscopic
examination of the urinary sediment (cystine crystals), screening for
crystalluria by cyanide-nitroprusside urine test, urinary amino acids
measurements by ion exchange chromatography, or liquid chromatography mass
spectrometry. Cystine-lysinuria also can be diagnosed by an oral lysine
loading test: urinary excretion of cystine and lysine is increased and, in
case of associated neurologic abnormalities, the EEG reveals mild background
slowing following lysine loading.
Peak times for clinical expression of cystinuria
are usually during the second and third decades of life (the disease may
appear as early as in the first year or as late as in the ninth decade of
life). Renal cholics with hematuria as a consequence of nephrolithiasis,
urinary tract infections, and obstructive uropathies are common
manifestations. Hypertension and renal failure occur occasionally. Onset of
neurologic symptoms, such as progressive loss of motor and cognitive
milestones, seizures, spasticity, and ataxia, have been reported to occur in
early childhood. Further deterioration of neurologic status often coincides
with urinary tract infections. Alteration of intestinal flora by neomycin
and Lactobacillus acidophilus may lessen the neurologic injury. Maintaining good hydration can help
reduce the risk of nephrolithiasis.
Assess renal function. If serum
creatinine levels are increased, obtain a creatinine clearance test and
request, if necessary, urology/nephrology consultation. Check serum
electrolytes, hemoglobin, and blood cell counts (frequent urinary tract
infections and hematuria). Leukopenia, agranulocytosis, or even aplastic
anemia are possible adverse effects of d-penicillamine treatment.
Severe allergic reactions, nephrotic syndrome with membranous
glomerulonephritis, bronchoalveolitis with respiratory distress, myasthenia
gravis, and dermatologic affections (e.g., pemphigoid, lupus erythematosus,
dermatomyositis) have been reported as a consequence of d-penicillamine treatment.
In the presence of an associated seizure
disorder (rare), ask about anticonvulsant therapy (efficacy and toxicity)
and check for treatment ...