Cystine disorders

1. Cystine disorders
 Both are +ve cyanide nitroprusside test (due to presence of cystine)
 Autosomal recessive inheritance
Cystinosis: (impaired of cystine utilization)
 Inborn error of metabolism, where cystine is incompletely metabolized result in cystine
deposition in different tissue
 Age: mostly child
 Clinical forms
1. Infantile (nephropathic) cystinosis
2. Late-onset cystinosis
3. Benign cystinosis.
 Presentation:
Infantile cystinosis is the most common and severe form of cystinosis.
Children appear normal at birth
At 9–10 months of age, there is excessive thirst and urination and failure to
thrive.
The abnormally high loss of phosphorus in the urine leads to rickets.
The longer-term manifestations of cystinosis
 Corneal crystals
 Renal involvement which if not treated lead to renal failure by age of
nine , also may lead to proximal tubular dysfunction (Fanconi syndrome)
 Hypothyroidism, hypogonadism and Impaired glucose tolerance
 Myopathy
 Dysphagia, hepatomegaly and splenomegaly
 Diagnosis
 Examining the eyes for the presence of corneal crystals
 Cystine measurement in blood cells, amniotic fluid cells, and chorionic
villi (100 times the level found in persons without this disorder).
 Treatment:
1. Rehydration and replacement of bicarbonate losses
2. Cysteamine eye drops (to dissolve of corneal crystals) or oral cysteamine (to
forms a complex with cystine that can leave lysosomes, ameliorating disease)
3. In ESRD ( dialysis or Kidney Transplantation )
4. N.B. Pencillamine has no role in cystinosis( use in treatment of cystinuria)
Cystinuria: (defect of cystine renal absorption)

2.  Presence of Cystine and other amino acid (Ornithine, Lysine and Arginine) in the urine
due to inability of renal tubules to reabsorb them lead to cystine stone formation
 Age: childhood and adolescence
 Presentation: flank pain with or without haematuria (stone)
 Diagnosis:
 Urine analysis (characteristic hexagonal crystals in urine )
 Increase cystine in urine 20 -30 x normal (>2mmol/day, NR <0.15)
 KUB radio-opaque calculi
 Treatment
 Increasing fluid intake (up to 4 L/d) and reducing sodium in the diet which may
lower urinary cystine concentrations.
 Urinary alkalinization with potassium citrate may increase the solubility of cystine
and decrease the risk of stone formation
 D-penicillamine ( 1 – 2g/day in four divided doses )can bind to the cysteine
molecules which form complex that is much more soluble than cystine, also can use
the Mercaptopropionylglycine
 Kidney transplantation or dialysis if progressed to ESRD
 N.B. Extracorporeal shock wave lithotripsy is not helpful.