TBMD Reclassified Heterozygous Alport COL4A4 — ESENeph MCQ

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HardGlomerulonephritisTBMD Reclassified Heterozygous Alport COL4A4ESENeph

A 22-year-old man presents with haematuria and proteinuria. His father has ESKD and hearing loss. Renal biopsy electron microscopy shows diffuse thinning of the glomerular basement membrane (uniformly <200 nm) without lamellation. Genetic testing shows a heterozygous COL4A4 variant. What is the current understanding of this finding?

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Correct answer: E — This represents heterozygous Alport syndrome (autosomal dominant) — requires lifelong monitoring for progressive CKD

The traditional term 'thin basement membrane disease' (TBMD, also called 'benign familial haematuria') is being reclassified. Patients with heterozygous COL4A3 or COL4A4 variants — previously labelled as TBMD carriers — are now recognised to have autosomal dominant Alport syndrome. While many remain stable with isolated haematuria, a significant proportion (~15-20%) develop proteinuria, hypertension, and progressive CKD over decades. The 2017 Alport Syndrome Classification Working Group recommended retiring the term 'thin basement membrane disease' in favour of 'heterozygous Alport syndrome' to ensure these patients receive appropriate monitoring. Lifelong follow-up with annual BP, eGFR, and uACR is essential. Early RASi if proteinuria develops.

Reference: Kashtan et al 2018 – Alport Reclassification; Savige et al 2022 – TBMD as Alport