Cystinosis

INTRODUCTION:
  • Cystinosis is an autosomal recessive disorder characterized by a defect in transport of cysteine across the lysosomal membrane.
  • Kidneys are affected due to deposition of cystine crystals in proximal tubule cells causing features of fanconi syndrome.
  • Renal calculi is not a feature of cystinosis.
  • Cystinosis: is caused by a defect in transport of cystine across the lysosomal membrane due to defective function of the lysosomal carrier protein cystinosin, resulting from mutations of the cystinosis gene (CTNS). (CTNS has been mapped to chromosome arm 17pl3).
  • The stored cystine is poorly soluble and crystallizes within the lysosomes of many cell types, leading to widespread tissue and organ damage.
TYPES
  • ee types: Thr of cystinosis have been described based on the age at diagnosis and magnitude of cellular cystine deposition:
  1. Infantile nephropathic form:the most common and the most severe,develop symptoms early in life and develop end-stage kidney failure by late childhood.
  2. Adolescent onset: is a more indolent form of the disease,features of disease are less severe, and end-stage renal disease occurs after age 15 years.
  3. Adult onset:does not include renal involvement and is limited to the eye (ocular cystinosis).
FANCONI SYNDROME:
  • In the infantile nephropathic form of cystinosis, the kidney is affected early in life by cystine crystals deposited in proximal tubule cells.
  • Fanconi's syndrome have defect in DNA repair mechanism 
  • Characterized by wasting of substances reabsorbed in this nephron segment, including sodium, potassium, phosphate, calcium, magnesium, bicarbonate, and others. 
  • Metabolic acidosis and electrolyte disturbances ensue and contribute to the stunting of growth in children with cystinosis.
  • Fanconi's syndrome is associated with malignancy
  • Cystinosis is the most common inherited cause of Fanconi syndrome.
  • Fanconi's syndrome is caused by Old and degraded tetracycline
  • Fanconi syndrome with nephrocalcinosis has a variant of dent disease shows Hypercalciuria,Proteinuria & Rickets
CLINICAL FEATURES:
  • A typical cystinotic patient has pale blond hair and blue eyes, and fair skin due to disturbances in pigment metabolism.
  • 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.
Eye
  • Severe photophobia,
  • Corneal ulcerations,
  • Retinal blindness
Liver disease
  • Hepatosplenomegaly,
  • Nodular degenerative hyperplasia
CNS involvement
  • Calcifications,
  • Atrophy,
  • Pseudotumor cerebri
Pancreatic disease
  • Exocrine insufficiency,
  • Insulin-dependent diabetes mellitus
DIAGNOSIS:
  • Confirmed by measuring cystine levels in polymorphonuclear leukocytes or cultured fibroblasts.
  • 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.
TREATMENT:
  • Oral cysteamine therapy:postpones the need for renal transplantation,should be initiated within days of diagnosis.
  • Renal transplantation:has prolonged the lives of children with cystinosis. Renal transplantation is high successful, disease does not recur in the graft, but cystine continues to accumulate in other tissues, resulting in complication
Exam Question
  • Fanconi syndrome with nephrocalcinosis has a variant of dent disease shows Hypercalciuria,Proteinuria & Rickets
  • Photophobia and blond hair, Presence of cystine within leukocytes & Fanconi syndrome are seen in cystinosis 
  • Fanconi's syndrome is caused by Old and degraded tetracycline
  • Fanconi's syndrome is associated with malignancy
  • Fanconi's syndrome have defect in DNA repair mechanism
Don't Forget to Solve all the previous Year Question asked on Cystinosis