Cystinosis

Cystinosis is a metabolic disorder characterizing by an accumulated cystine in various organs and tissues leading to potential intense organ malfuncti

Cystinosis (Cys)

 

Cystinosis is a metabolic disorder characterizing by an accumulated cystine in various organs and tissues leading to potential intense organ malfunction including end-stage kidney failure (ESKF).

 

Cys is an autosomal recessive trait that’s related to genetic mutation of the👉 CTNS gene that encodes cystinosin. The latter is a novel transporter that’s responsible for extracting cystine from lysosomes.  Cys is classified into 3 forms according to the age of presentation & intensity of Sms:

1)    Infantile (nephropathic) form,

2)    Late-onset (juvenile) form, &

3)    Adult (benign) form.

 

Infantile cystinosis is the most common with severely presented phenotype. Ptns present between 3 & 6 mo of age with Sns & Sms due to renal tubular malfunction that may include polyuria, polydipsia, poor weight gain, vomiting, malaise, pyrexia of unknown origin, & acute episodic hypovolemia. Affected children would exhibit progressive decline in the eGFR, leading to ESRD within 10 ys of age. Extra-renal findings may include ocular disorders, hepatomegaly, hypothyroid disease, muscle weakness, & stunted growth. However, cognitive function is normal in children, despite CNS complications can be observed after the age of 20 ys. In involved males, delay in puberty is commonly reported.  

 

Late-onset (juvenile) cystinosis often seen around 8 years old manifesting by renal tubular dysfunction. Ptns also show progressive drop in GFR, leading to ESRD by 15 ys of age.  

Adult cystinosis is mostly benign type. Ptns usually asymptomatic with exception of photophobia or ocular discomfort due to corneal crystal deposition.  

 

Dgx of cystinosis can be established in THREE ways:👉

1)    Increased intra-leukocyte cystine contents,

2)    Recognition of cystine corneal crystals by slit lamp testing, &

3)    Recognition of CNTS genetic mutations.  

 

Treatment: ALL cases with cysteamine once the Dgx of Cys has been established. Early therapy with cysteamine could:👉

1)    Preserve kidney function,

2)    Correct hypothyroidism,

3)    Limit ocular discomfort,

4)    Improve visual acuity,

5)    Enhance growth & patient survival.  

6)    With ESRD, RTx is the preferrable with favourable outcome.