Makindo Medical Notes.com

There is hereditary nephritis, haematuria, progressive renal failure and high-frequency sensorineural deafness usually more marked in males.

About

• The aetiology was discovered when researchers noticed that the GBM in Alport's did not bind the Anti-GBM antibodies seen in Goodpasture's syndrome
• This finding suggested an abnormality in type IV collagen, against which the anti-GBM antibodies are directed.

Aetiology

• Traditionally X linked inherited disease affecting adults mainly males
• Other forms with AR and AD inheritance are seen
• Mutation in the COL4A5 gene on the X chromosome
• Leads to faulty Collagen Type IV - the type of collagen in Basement membranes
• There is degeneration of the glomerular basement membrane due to abnormal Type IV collagen

Mutations or Deletions

• COL4A5 on X chromosome which encodes Type 4 Collagen
• COL4A3 on X chromosome which encodes Type 4 Collagen
• COL4A4 on X chromosome which encodes Type 4 Collagen

Clinical

• Some have an associated sensorineural deafness
• Present with haematuria which can lead to end-stage renal failure
• Nephritis - abnormal GBM
• Deafness - sensorineural
• Ocular problems - Anterior lenticonus
• Female carriers have less severe disease

Investigations

• Urinary dipstick test - protein and blood
• 24-hour urine specimen for protein and creatinine
• Urinary sediment should be analysed by microscope to detect dysmorphic red blood cells and red blood cell casts
• Renal USS: size is usually normal and then smaller with disease progression
• Genetic analysis: can be used but limited usefulness
• Skin biopsy - the absence of alpha-5 (IV) chains of type IV collagen in the epidermal
• Renal Biopsy - Electron microscopy reveals diffuse thickening and splitting of the basement membrane

Management

• No specific treatment except renal replacement.
• ACEI may help and may slow but not prevent disease
• They are young and otherwise well and are good candidates for renal transplant
• Small chance that they react against the normal GBM in the transplanted kidney
• Anti-GBM antibody disease usually occurs in the first year after transplantation in 3-4%