Laboratory Studies
Serum electrolyte measurements are used to detect the presence of acidosis (hyperchloremic, normal anion gap [see the Anion Gap calculator]) and severity of hypokalemia, hyponatremia, hypophosphatemia, and low bicarbonate concentration in patients with cystinosis.
Blood gases may be used to detect metabolic acidosis and the degree of respiratory compensation.
Urine testing reveals low osmolality, glucosuria, and tubular proteinuria (including generalized amino aciduria).
Measurements of urine electrolytes serve to detect the loss of bicarbonate and phosphaturia.
Diagnosis of cystinosis is confirmed by measuring cystine levels in polymorphonuclear leukocytes or cultured fibroblasts. Cystine concentrations in individuals who are homozygous for cystinosis are 5-10 nmol half-cystine/mg cell protein; in heterozygous individuals, the levels are less than 1 nmol half-cystine/mg cell protein. Reference range levels are below 0.2 nmol half-cystine/mg cell protein.
When a fetus is at risk for cystinosis, the cystine level can be measured in chorionic villi or cultured amniotic fluid cells.
Imaging Studies
Renal ultrasonography should be obtained in patients with elevated urine calcium excretion to rule out nephrocalcinosis.
Radiography for kidneys, ureters, and bladder (KUB) may be needed to evaluate possible urinary tract calcifications in patients with hypercalciuria or as a diagnostic evaluation of severe abdominal pain.
CT scanning and MRI are used to evaluate adult patients with infantile nephropathic cystinosis who have CNS symptoms.
Other Tests
Slit-lamp examination of the eyes reveals corneal and conjunctival cystine crystals (pathognomonic for cystinosis) as early as age 1 year, although photophobia does not usually become apparent until age 3-6 years.
Examination of the eye fundi may reveal the presence of peripheral retinopathy that is more severe on the temporal than on the nasal side. In some patients, retinopathy may lead to blindness.
Histologic Findings
The kidney appears particularly susceptible to the adverse effects of cystine accumulation in cystinosis. The morphologic changes in the kidney vary with the stage of the disease.
Early in the course of the disease, renal tubules are disorganized and poorly developed, even before the clinical onset of Fanconi syndrome. A "swan neck" deformity, or thinning of the first part of proximal convoluted tubule develops after age 6 months and becomes apparent during the first years of life, correlating with the clinical onset of the Fanconi syndrome; however, this finding is not unique to cystinosis.
Swan neck lesions are characterized by thinning of the tubular epithelial cells and progression to glomerulo-tubular disconnection, leading to formation of atubular glomeruli. Disconnection of glomeruli from the tubules leads to failure of filtration from that nephron. Widespread atubular glomeruli result in progressive failure of filtration. Progressive formation of atubular glomeruli may explain slow progression to end-stage renal disease.
A cystinotic kidney manifests different stages of destruction, depending on the stage of chronic kidney injury. Giant cell transformation of the glomerular visceral epithelium with occasional peculiar "dark" cells (unique to the cystinotic kidney) and cytoplasmic inclusions may be seen. Hyperplasia and hypertrophy of the juxtaglomerular apparatus may correlate with functional alterations of the renin-angiotensin system. With the help of polarizer attachment to the light microscope, birefringent rectangular to polygonal crystals of cystine are readily apparent, especially in interstitial cells, but they have also been observed in glomerular and tubular cells.
Later in the course of cystinosis, in the uremic phase, varying degrees of global and segmental sclerosis, tubular atrophy and degeneration, chronic interstitial nephritis, interstitial fibrosis, and abundant crystal deposition are pronounced. The kidneys are small, echodense, and have a tendency to form cysts. Kidneys from patients with late-onset nephropathic disease resemble those with advanced changes in the infantile form.
In order to see cystine crystals, the biopsy sample must be fixed in ethanol, not in an aqueous solution, because water dilutes crystals. In general, a kidney biopsy is not necessary in cystinosis, unless the renal disease deviates from the expected course.
Kidneys from patients with benign adult cystinosis do not demonstrate any abnormalities.
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An 8-month-old male infant at the time his cystinosis is diagnosed.
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The same child as in the previous image, at age 20 months, fed via gastric tube.
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The same child as in the previous images, at age 3 years, fed via jejunal tube.
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The same child as in the previous images, at age 4 years, on total parenteral nutrition via central line.
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The same child as in the previous images, at age 9 years, off total parenteral nutrition for 1 year and tolerating oral intake.
