Alport Syndrome
Basics
Description
- A group of genetic diseases with defects in one of several subunits of type IV collagen that cause progressive hematuric nephritis and sensorineural deafness
- Genetically heterogeneous defined as three types:
- X-linked trait (XLAS): 80%
- Autosomal recessive (ARAS): 15%
- Autosomal dominant (ADAS): 5%
Epidemiology
- Varies according to genetics. Gene frequency is 1:5,000.
- Gender
- XLAS is more severe in males than females.
- ARAS is equally severe in males and females.
- Age
- Hematuria: 1st year of life (XLAS)
- Hearing loss and ocular abnormalities: late childhood or early adolescence
- End-stage kidney disease (ESKD) by age 40 years in 90% of XLAS
Prevalence
- In the United States, 3% of children and 0.2% of adults with ESKD:
- 0.02% of the population
- In Europe: 2.3% of patients with ESKD
Etiology and Pathophysiology
- Mutations arrest the normal development of collagen in glomerular basement membrane (GBM) in cochlea and lens capsule:
- Glomerular membranes thicken unevenly, split, and ultimately deteriorate.
- This leads to mild proteinuria and sclerosis, with progression from concomitant interstitial nephritis and renal fibrosis.
- X-linked dominant inheritance (XLAS)
- Mutations in the COL4A5 gene encoding the α-5(IV) collagen chain on chromosome Xq26-48
- Autosomal recessive inheritance (ARAS)
- Mutations in the COL4A3 or COL4A4 gene encoding the 3(IV) or 4(IV) chain, respectively, on chromosome 2q35-37
Genetics
See “Description.”
Risk Factors
- For renal deterioration:
- Clinical manifestations
- Hypertension
- Presence of nephrotic syndrome
- Clinical manifestations
- Family history
- Juvenile type: stereotypical course ESKD <20 years
- “Nonprogressive” or adult type: variable course ESKD: age 40 years
- Gender
- XLAS is more severe; male > female; 90% males versus 15% females go to ESKD
- ARAS: male = female
- Type of inheritance
- XLAS males and ARAS have a more severe disease than ADAS.
- Type of mutations in type IV collagen genes
General Prevention
Commonly Associated Conditions
- Hearing defects
- Sensorineural deafness
- Frequent but not universal
- Cochlear lesion
- Sensorineural deafness
- Ocular manifestations
- Anterior lenticonus
- 25% of patients
- Pathognomonic feature
- Dot-and-fleck retinopathy
- Posterior polymorphous corneal dystrophy
- Anterior lenticonus
- Leiomyomatosis: 2–5% of families
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Citation
Domino, Frank J., et al., editors. "Alport Syndrome." 5-Minute Clinical Consult, 33rd ed., Wolters Kluwer, 2025. Medicine Central, im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/816251/all/Alport_Syndrome.
Alport Syndrome. In: Domino FJF, Baldor RAR, Golding JJ, et al, eds. 5-Minute Clinical Consult. Wolters Kluwer; 2025. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/816251/all/Alport_Syndrome. Accessed December 12, 2024.
Alport Syndrome. (2025). In Domino, F. J., Baldor, R. A., Golding, J., & Stephens, M. B. (Eds.), 5-Minute Clinical Consult (33rd ed.). Wolters Kluwer. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/816251/all/Alport_Syndrome
Alport Syndrome [Internet]. In: Domino FJF, Baldor RAR, Golding JJ, Stephens MBM, editors. 5-Minute Clinical Consult. Wolters Kluwer; 2025. [cited 2024 December 12]. Available from: https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/816251/all/Alport_Syndrome.
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