eMedicine Specialties > Pediatrics: General Medicine > Nephrology

Cystinosis: Differential Diagnoses & Workup

Author: Ewa Elenberg, MD, Assistant Professor, Department of Pediatrics, Renal Section, Texas Children's Hospital, Baylor College of Medicine
Contributor Information and Disclosures

Updated: Aug 31, 2009

Differential Diagnoses

Other Problems to Be Considered

Cystinosis may initially be misdiagnosed as dehydration caused by vomiting and diarrhea, failure to thrive, fever of unknown origin, Bartter syndrome, diabetes mellitus, diabetes insipidus, dwarfism, rickets, or brain tumor.

Workup

Laboratory Studies

  • Serum electrolyte measurements are used to detect the presence of acidosis (hyperchloremic, normal anion gap) 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, becomes apparent during the first years of life and correlates with the clinical onset of the Fanconi syndrome, although this finding is not unique to cystinosis. A cystinotic kidney manifests different stages of destruction, with giant cell transformation of the glomerular visceral epithelium and occasional peculiar "dark" cells (unique to the cystinotic kidney) and cytoplasmic inclusions. 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.

More on Cystinosis

Overview: Cystinosis
Differential Diagnoses & Workup: Cystinosis
Treatment & Medication: Cystinosis
Follow-up: Cystinosis
Multimedia: Cystinosis
References
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References

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Further Reading

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Keywords

cystinosis, cystine storage disease, Fanconi syndrome, infantile cystinosis, infantile nephropathic cystinosis, adolescent cystinosis, adult cystinosis, ocular cystinosis, end-stage kidney failure, cysteine, metabolic acidosis, electrolyte disturbances, renal transplantation, ocular cystinosis, polyuria, polydipsia, dehydration, normal anion gap hyperchloremic acidosis, hypophosphatemic rickets, failure to thrive, severe photophobia, corneal ulcerations, retinal blindness, delayed puberty, hypothyroidism, pancreatic disease, exocrine insufficiency, insulin-dependent diabetes mellitus, hepatosplenomegaly, nodular degenerative hyperplasia, distal vacuolar myopathy, calcifications, atrophy, pseudotumor cerebri, polydipsia, polyuria, renal tubular abnormalities

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Contributor Information and Disclosures

Author

Ewa Elenberg, MD, Assistant Professor, Department of Pediatrics, Renal Section, Texas Children's Hospital, Baylor College of Medicine
Ewa Elenberg, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, and American Society of Nephrology
Disclosure: Nothing to disclose.

Medical Editor

Uri S Alon, MD, Director of Research and Education, Department of Pediatrics, Division of Pediatric Nephrology, Children's Mercy Hospital of Kansas City; Professor, University of Missouri at Kansas City
Uri S Alon, MD is a member of the following medical societies: American Federation for Medical Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Adrian Spitzer, MD, Professor, Department of Pediatrics, Albert Einstein College of Medicine; Director of NIH Training Program, Children's Hospital at Montefiore Medical Center
Adrian Spitzer, MD is a member of the following medical societies: American Academy of Pediatrics, American Federation for Medical Research, American Pediatric Society, American Society of Nephrology, American Society of Pediatric Nephrology, International Society of Nephrology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Howard Trachtman, MD, Program Director, Pediatrics Research, Schneider Children's Hospital, Department of Pediatrics, Division of Nephrology, Professor, Albert Einstein College of Medicine
Howard Trachtman, MD is a member of the following medical societies: American Society of Hypertension, American Society of Nephrology, American Society of Pediatric Nephrology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Chief Editor

Craig B Langman, MD, The Isaac A Abt, MD, Professor of Kidney Diseases, Feinberg School of Medicine, Northwestern University; Division Head of Kidney Diseases, Children's Memorial Hospital, Chicago
Craig B Langman, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Nephrology, and International Society of Nephrology
Disclosure: Amgen Grant/research funds None; Altus Pharmaceuticals Grant/research funds None; Genzyme Grant/research funds None; Merck Grant/research funds None; NIH Grant/research funds None

 
 
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