Makindo Medical Notes

Related Subjects: |Metabolic acidosis |Lactic acidosis |Acute Kidney Injury (AKI) / Acute Renal Failure

Alport's syndrome 🧬 is a hereditary disorder of the glomerular basement membrane (GBM), characterized by nephritis 🩸, haematuria 🚽, progressive renal failure 🩺, and high-frequency sensorineural deafness 👂. Males are more severely affected due to the typical X-linked inheritance.

About 📖

• The disease was first recognized when researchers observed that the GBM in Alport’s did not bind anti-GBM antibodies (as seen in Goodpasture’s syndrome).
• This pointed to an abnormality in Type IV collagen 🧩, the key protein in basement membranes of the kidney, ear, and eye.

Aetiology 🔬

• Most often X-linked recessive inheritance (≈80%), predominantly affecting males 👦.
• Also has autosomal recessive (AR) and autosomal dominant (AD) forms.
• COL4A5 mutation (X-linked), or mutations in COL4A3 / COL4A4 (AR/AD forms), → abnormal collagen IV → progressive GBM degeneration.

Clinical Features 🩺

• Renal: Persistent microscopic or macroscopic haematuria 🚽, progressing to end-stage renal disease (ESRD) in many patients.
• Hearing loss: Bilateral high-frequency sensorineural deafness 👂, usually emerging in adolescence.
• Ocular: Anterior lenticonus 👁️ (pathognomonic), retinal flecks, and recurrent corneal erosions.
• Family history: Often positive for kidney disease and deafness across generations.
• Female carriers 👩 may have haematuria but slower progression (due to lyonization of X-chromosome).

Investigations 🔍

• Urinalysis: Proteinuria and haematuria (dysmorphic red cells, red cell casts).
• Renal function: Rising creatinine with CKD progression.
• Renal USS: Kidneys usually normal-sized early on, later contracted.
• Genetic testing: COL4A mutations, increasingly used for diagnosis.
• Skin biopsy: May show absence of α5(IV) collagen in epidermis.
• Renal biopsy: EM shows pathognomonic GBM thickening, splitting, and lamellation (“basket-weave appearance”).

Management ⚕️

• Supportive CKD management: BP control, salt restriction, avoid nephrotoxins.
• ACE inhibitors / ARBs: Can reduce proteinuria and slow progression 🧪.
• Hearing aids & ophthalmology follow-up: For non-renal manifestations 👂👁️.
• Renal replacement therapy: Dialysis or transplant when ESRD develops. Patients are often young and otherwise fit, making them good transplant candidates.
• Post-transplant risk: 3–4% develop anti-GBM nephritis ⚠️ within the first year, as the immune system recognizes the “normal” donor GBM as foreign.

Key Clinical Pearls ✨

• Think of Alport’s in a young male with haematuria 🚽 + renal failure 🩺 + deafness 👂 ± ocular features 👁️.
• Basket-weave GBM on EM = diagnostic clue 🔬.
• Unlike Goodpasture’s, antibody staining is negative 🚫 — it’s a structural defect, not an antibody attack.