The following are true of cystinuria, except:
A. Cystinuria is inherited as an autosomal dominant condition with an incidence of 1 in 20,000Answer A
Cystinuria like most inborn errors of metabolism is inherited in an autosomal recessive pattern with the gene defect located on Chromosome 2. It has been classified into three types (I, II and III) according to the specific gene mutation although this differentiation is of little clinical relevance. The incidence of heterozygous cystinuria is about 1 in 20,000 and these individuals are at high risk of recurrent cystine urolithiasis. Patients with cystinuria have defective absorption in the jejunum of cystine, and the other dibasic amino acids ornithine, lysine and arginine. The reabsorption of these amino acids in the proximal convoluted tubule of the kidney is also abnormal leading to high levels in the urine. Cystine, in contrast to ornithine, lysine and arginine, is relatively insoluble at physiological urine pH and has a pKa of 8.3. At pH < 7.0 the solubility of cystine is approximately 250 mg/L but at pH > 7.5 its solubility increases considerably to more than 500 mg/L. Patients with heterozygous cystinuria excrete <200 mg/day and usually do not form stones whereas cystine excretion in homozygous cystinurics is typically 600–1400 mg/day.
Cystinurics usually present with their first stone episode in the second or third decade of life and represent a particularly challenging group of patients to treat. Cystine stones may be managed surgically by ESWL, URS, PCNL although ESWL may be less effective because they are hard. Also, cystine stones are poorly radio-opaque as they do not contain calcium and are visible only because of the disulphide bonds between the cysteine molecules.
Prevention of stone formation is the primary objective and patients should be advised to maintain a fluid intake of 2.5–3.0 L/day. They should also be referred to a dietician who will recommend a low methionine diet. Methionine, which is metabolised to cystine, is found in high concentrations in animal protein which should therefore be restricted. Patients are advised to alkalinise their urine with potassium citrate solution (10 mL tds) aiming for pH 7.0–8.0. However, potassium citrate solution is unpalatable and often poorly tolerated. An alternative, although not readily available in the UK, is potassium citrate tablets. When these measures fail to adequately prevent stone formation, drugs which bind to cystine and thereby increase its solubility may be considered. D-Penicillamine binds cystine but is associated with considerable side effects such as skin rash, oral ulceration and gastrointestinal upset and has largely been superseded by tiopronin (Thiola) 1000 mg/day in divided doses. Vitamin C may increase the solubility of cystine but in high doses can cause hyperoxaluria that may predispose to stones of other types.