Makindo Medical Notes

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

Alport's syndrome is a hereditary condition characterized by nephritis, haematuria, progressive renal failure, and high-frequency sensorineural deafness, which is usually more pronounced in males.

About

• The aetiology was discovered when researchers noticed that the glomerular basement membrane (GBM) in Alport's syndrome did not bind anti-GBM antibodies as seen in Goodpasture's syndrome.
• This finding suggested an abnormality in type IV collagen, which is the target of anti-GBM antibodies in Goodpasture's syndrome.

Aetiology

• Traditionally an X-linked inherited disease, affecting adults, predominantly males.
• There are also autosomal recessive (AR) and autosomal dominant (AD) forms of the disease.
• Mutation in the COL4A5 gene on the X chromosome leads to faulty collagen type IV, a key component in basement membranes.
• As a result, there is degeneration of the glomerular basement membrane due to the abnormal type IV collagen.

Mutations or Deletions

• COL4A5 on the X chromosome, encoding type IV collagen.
• COL4A3 and COL4A4 on the X chromosome, also encoding type IV collagen.

Clinical Features

• Some individuals also have associated sensorineural deafness.
• Presents with haematuria which can progress to end-stage renal failure.
• Patients often have nephritis due to the abnormal GBM.
• Ocular problems, such as anterior lenticonus, may be present.
• Female carriers tend to have a less severe disease course.

Investigations

• Urinary dipstick test to check for protein and blood.
• A 24-hour urine specimen to measure protein and creatinine levels.
• Urinary sediment analysis by microscopy to detect dysmorphic red blood cells and red blood cell casts.
• Renal ultrasound (USS): kidneys are usually normal-sized, though they become smaller with disease progression.
• Genetic analysis may be used, though its usefulness is limited.
• A skin biopsy may show the absence of alpha-5 (IV) chains of type IV collagen in the epidermis.
• Renal biopsy: Electron microscopy reveals diffuse thickening and splitting of the basement membrane.

Management

• There is no specific treatment other than renal replacement therapy (dialysis or transplant).
• ACE inhibitors (ACEI) may help and can slow disease progression, but they cannot prevent it.
• Patients are generally young and otherwise healthy, making them good candidates for a renal transplant.
• There is a small chance (3-4%) of developing anti-GBM antibody disease within the first year after transplantation, where the body reacts against the normal GBM in the transplanted kidney.