Cystinosis Clinical Presentation

Updated: Dec 05, 2020
  • Author: Ewa Elenberg, MD, MEd; Chief Editor: Craig B Langman, MD  more...
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Cystinosis is classified into 2 general phenotypes: nephropathic and nonnephropathic cystinosis (benign variant).

  • Nephropathic cystinosis is further subdivided into infantile and late-onset (intermediate cystinosis), based on the age at presentation.

    • Nephropathic infantile cystinosis is the most common and most severe variant.

      • Symptoms of multiorgan involvement may be mild to severe, depending on the patient's age at diagnosis, the age when treatment was instituted and genetic factors.

      • Early in the natural history of infantile nephropathic cystinosis, clinical involvement follows a fairly predictable chronology. Patients usually present during the first year of life with polyuria, polydipsia, dehydration, metabolic acidosis (normal anion gap hyperchloremic acidosis), hypophosphatemic rickets, failure to thrive, and laboratory findings consistent with Fanconi syndrome. If untreated, renal failure develops by age 7-10 years.

      • Oral cysteamine therapy postpones the need for renal transplantation.

      • Renal transplantation has prolonged the lives of children with cystinosis. Renal transplantation is highly successful, disease does not recur in the graft, but cystine continues to accumulate in other tissues, resulting in such complications as eye disease (eg, severe photophobia, corneal ulcerations, retinal blindness), delayed puberty, hypothyroidism, pancreatic disease (eg, exocrine insufficiency, insulin-dependent diabetes mellitus), liver disease (eg, hepatosplenomegaly, nodular degenerative hyperplasia), distal vacuolar myopathy, swallowing difficulties, and CNS involvement (eg, calcifications, atrophy, pseudotumor cerebri).

    • Late-onset (intermediate) nephropathic cystinosis is a more indolent form of the disease. The age at manifestation is later; most commonly in early adolescence. Symptoms are usually restricted to kidneys (eg, less severe form of Fanconi syndrome, proteinuria) and eyes (eg, photophobia). Progression of the disease is slower; end-stage renal disease (ESRD) occurs after age 15 years.

  • Nonnephropathic cystinosis is considered a benign variant and is usually diagnosed by an ophthalmologist treating patients for photophobia. Photophobia may not begin until middle age and is not usually as debilitating as in the nephropathic form of the disease. Slit-lamp examination reveals corneal crystal deposits. In addition to the eye, cystine crystals are present in the bone marrow and leukocytes but are absent in the kidney and the retina.


Physical Examination

A typical cystinotic patient has pale blond hair and blue eyes, although the disease also occurs among dark-haired individuals with brown eyes.

  • Initial presentation of infantile nephropathic cystinosis

    • The initial symptoms include polydipsia, polyuria, vomiting, loss of appetite, constipation, and failure to thrive.

    • The first signs may go unrecognized for several months until the patient develops severe dehydration, electrolyte imbalance, and metabolic acidosis during a mild illness. Some children may have recurrent bouts of fever and manifestations of heat intolerance (becoming red like beets) caused by a defect in sweat production.

    • Patients typically have short stature and renal Fanconi syndrome.

    • They have poor appetite, crave salty and hot and spicy foods, and prefer specific food textures. Each patient has specific food preferences that may already be evident by age 2 years.

  • Initial presentation of late-onset nephropathic (intermediate) cystinosis

    • Most cases are diagnosed by age 12 years.

    • Complete Fanconi syndrome often does not develop in late-onset cystinosis, but renal function deteriorates as in infantile nephropathic cystinosis, and patients often experience end-stage renal failure within a few years of diagnosis.

  • Nephropathic cystinosis (progressive disease)

    • Children younger than 1 year usually show growth retardation, rickets, metabolic acidosis, and other chemical evidence of renal tubular abnormalities, such as increased renal excretion of glucose, amino acids, phosphate, and potassium. They may require frequent hospital admissions because of dehydration.

    • As children age, failure to thrive is prominent. Without specific therapy, children remain below the third percentile in both height and weight throughout life.

    • Corneal crystals are apparent by age 1-2 years. The untreated cornea is packed with crystals by age 3-4 years, leading to photophobia in early childhood.

    • By age 7-10 years, previously noted symptoms become more severe, and patients develop increased proteinuria, progressive renal failure, increased photophobia, and thyroid insufficiency.

    • ESRD develops in adolescence, usually at age 10-13 years. The good adherence to therapy slows down the progression of renal failure by several more years.

    • Sexual maturation is delayed.

    • Males have hypogonadism and are infertile.

    • Retinal damage does not occur until the second or third decade of life.

    • Cerebral calcifications and muscular and swallowing difficulties cluster around the third decade of life.

    • The major complication of cystinosis in patients older than 20 years is legal blindness, distal vacuolar myopathy, cerebral calcifications or atrophy, swallowing dysfunction, diabetes mellitus, and liver disease (eg, hepatomegaly, nodular degenerative hyperplasia).