Cystinosis Flashcards
A 9-month-old boy presents with poor feeding, vomiting, excessive thirst, and polyuria. His growth is below the 5th percentile for his age. Physical examination reveals photophobia but no other significant findings. Laboratory studies show hypokalemia, hypophosphatemia, metabolic acidosis, and evidence of Fanconi syndrome. A slit-lamp examination reveals cystine crystals in the cornea. Which of the following is the most likely underlying defect?
A) Defective reabsorption of cystine in the proximal renal tubules
B) Impaired transport of cystine out of lysosomes
C) Deficient activity of ornithine transcarbamylase
D) Defective conversion of homocysteine to cystathionine
E) Impaired metabolism of branched-chain amino acids
Answer: Impaired transport of cystine out of lysosomes
Explanation: Cystinosis is an autosomal recessive lysosomal storage disorder caused by defective transport of cystine out of lysosomes. This leads to the accumulation of cystine crystals in various tissues, including the cornea and renal proximal tubules, causing Fanconi syndrome (loss of glucose, phosphate, bicarbonate, and amino acids in the urine). Key features include growth failure, polyuria, polydipsia, photophobia, and progressive renal failure. Diagnosis is confirmed by slit-lamp examination and elevated cystine content in leukocytes. Treatment with cysteamine helps reduce cystine accumulation.
Incorrect Answers:
A) Defective reabsorption of cystine in the proximal renal tubules occurs in cystinuria, which causes recurrent cystine kidney stones but does not result in systemic symptoms like photophobia or Fanconi syndrome.
C) Ornithine transcarbamylase deficiency causes hyperammonemia and orotic aciduria, not Fanconi syndrome.
D) Defective conversion of homocysteine to cystathionine is seen in homocystinuria, which presents with thromboembolism and ectopia lentis, not cystine crystal accumulation.
E) Impaired metabolism of branched-chain amino acids occurs in maple syrup urine disease, leading to neurological symptoms and sweet-smelling urine, not Fanconi syndrome or photophobia.
What is the genetic inheritance pattern of Cystinosis?
Autosomal recessive
What is the underlying pathophysiology of Cystinosis?
Defective transport of cystine out of lysosomes, leading to cystine crystal accumulation in lysosomes and cellular dysfunction
What are the clinical forms of Cystinosis, and which is the most severe?
Three forms: infantile (most severe), juvenile, and ocular (adult)
What are the key clinical features of Cystinosis?
Growth faltering, vomiting, polyuria, polydipsia, photophobia, progressive renal failure, hepatomegaly
What are the diagnostic findings associated with Cystinosis?
Observation of cystine crystals in the cornea under slit-lamp examination, elevated cystine content in leukocytes, progressive decline in GFR
What is the role of cysteamine in the treatment of Cystinosis?
Cysteamine reduces cystine accumulation in lysosomes by converting cystine to a more easily excreted form
What complications arise from untreated Cystinosis?
Progressive renal failure, metabolic acidosis, and multi-organ damage (e.g., hepatomegaly)
What organ systems are commonly affected in Cystinosis?
Kidneys (proximal tubules), cornea, liver, and other organs
