Makindo Medical Notes

Cystinosis is a rare autosomal recessive lysosomal storage disorder caused by defective cystine transport. It leads to accumulation of cystine crystals in multiple organs, causing progressive tissue damage. The nephropathic (infantile) form is the most severe, often presenting with Fanconi syndrome and progressing to kidney failure.

🧬 About

• Autosomal recessive disorder caused by mutations in the CTNS gene (encodes cystinosin, a lysosomal transporter).
• Abnormal accumulation of cystine (an amino acid) within lysosomes.
• Cystine is insoluble → crystal deposition → multi-organ damage.
• May cause proximal tubular dysfunction → Fanconi syndrome (loss of glucose, amino acids, bicarbonate, and phosphate in urine).

⚠️ Types of Cystinosis

• Nephropathic Cystinosis (Infantile form): Most common and severe. Symptoms appear within the 1st year (polyuria, dehydration, rickets). Progresses to ESRF by ~10 years if untreated.
• Intermediate Cystinosis (Juvenile/Late-Onset): Presents later (childhood/adolescence) with slower progression. CKD appears in late teens or early adulthood.
• Non-Nephropathic (Ocular/Adult): Milder form. Predominantly causes corneal deposits and photophobia. Kidney function remains preserved.

🩺 Clinical Features

• Renal: Polyuria, polydipsia, dehydration, metabolic acidosis (proximal RTA), hypophosphataemic rickets, CKD.
• Ocular: Corneal cystine crystals → photophobia, visual impairment.
• Endocrine: Hypothyroidism, hypogonadism, growth retardation.
• Other systemic: Hepatomegaly, splenomegaly, muscle wasting, difficulty swallowing (due to oesophageal involvement).

🔎 Investigations

• White cell cystine level: Gold standard diagnostic test.
• Genetic testing: Detects CTNS gene mutation, confirms diagnosis, helps family screening.
• Urine tests: Generalised aminoaciduria, glucosuria, tubular proteinuria.
• VBG: Proximal RTA → hyperchloraemic normal-anion-gap acidosis, hypokalaemia, hypouricaemia.
• Kidney function: Assess CKD and progression.
• Ophthalmology: Slit-lamp exam to detect corneal cystine crystals.

💊 Management

• Cysteamine therapy: Depletes cystine in lysosomes → slows progression of renal disease and extra-renal complications.
• Supportive therapy for Fanconi syndrome:
  • Electrolyte and bicarbonate replacement
  • Phosphate and vitamin D for rickets
• Renal replacement: Dialysis or kidney transplant in ESRF (transplant corrects kid