From the Guidelines
Cystinosis and cystinuria are two distinct genetic disorders with different pathophysiologies and clinical manifestations, requiring different management approaches to improve morbidity, mortality, and quality of life. Cystinosis is a lysosomal storage disease caused by mutations in the CTNS gene, leading to cystine accumulation within lysosomes of cells throughout the body, resulting in progressive organ damage, particularly to the kidneys, eyes, and thyroid [@\1@]. In contrast, cystinuria is a transport disorder affecting the kidneys' ability to reabsorb cystine and dibasic amino acids in the proximal tubule, causing excessive cystine excretion in urine and leading to recurrent kidney stone formation [@\2@].
Key differences in clinical presentation
- Cystinosis: characterized by renal Fanconi syndrome in childhood, with symptoms including polyuria, polydipsia, growth retardation, and eventual kidney failure
- Cystinuria: patients experience typical stone symptoms like flank pain, hematuria, and urinary tract infections
Management approaches
- Cystinosis: treatment involves cysteamine (Cystagon or Procysbi) to remove cystine from lysosomes, and kidney transplantation for end-stage renal disease
- Cystinuria: management focuses on preventing stone formation through high fluid intake, urinary alkalinization with potassium citrate, and sometimes thiol-binding drugs like d-penicillamine or tiopronin to increase cystine solubility [@\1@, @\2@]
Importance of dietary modifications
- Patients with cystinuria should limit sodium and protein intake, as high fluid intake is crucial to decrease urinary cystine concentration below 250 mg/L [@\1@]
- A reasonable goal for sodium intake in individuals with cystinuria is 100 mEq (2,300 mg) or less daily [@\1@]
Pharmacological therapy
- Tiopronin is possibly more effective and associated with fewer adverse events than d-penicillamine and should be considered first for patients with cystine stones who are unresponsive to dietary modifications and urinary alkalinization [@\2@]
From the Research
Differences between Cystinosis and Cystinuria
- Cystinosis is a rare autosomal-recessive lysosomal storage disease caused by mutations in the CTNS gene, leading to lysosomal cystine accumulation 1, 2, 3.
- Cystinuria, on the other hand, is an inherited disorder of the dibasic amino acid transport system in the proximal tubule and the small intestine, caused by mutations in the SLC3A1 and SLC7A9 genes 4.
- The main difference in pathophysiologic mechanisms is that cystinosis is a disease of cystine storage, while cystinuria is a disease of renal tubular cystine transport 5.
- Cystinosis uniformly results in the need for renal allograft, despite recent advances in medical therapy, while cystinuria has a variable severity of expression and may be amenable to long-term medical treatment in some patients 5.
- Cystinosis affects multiple organs, including the kidneys, eyes, thyroid, pancreas, gonads, muscles, and CNS, while cystinuria primarily affects the kidneys and is characterized by stone formation due to the inability of renal tubules to reabsorb cystine 1, 3, 4.