Background: A 19-year-old college student visits the nephrologist with his mom after getting referred from his pediatrician after noticing urine that was reddish-pink. He has been healthy and has been training for a marathon. The provider notices the patient is wearing hearing aids, and the mother confirms the patient was diagnosed with sensorineural deafness as a child. They read on the internet that Alport syndrome can present this way.

Young man with a musical instrument wearing hearing aids. Does he have Alport syndrome? — The young man has hearing aids and kidney dysfunction. Does he have Alport syndrome?

The nephrologist orders some tests which reveal a creatinine of 1.2 mg/dl (CKD Stage 2). The urinalysis shows 12 red blood cells per high-powered field and 3+ protein.

They are not aware of any Alport’s diagnoses in the family. But some extended relatives on the patient’s mother’s side have required a kidney transplant for CKD.

Please answer the following questions:

What is the most definitive way to evaluate for Alport syndrome in this patient?
* Kidney biopsy
* Genetic testing
* No further testing is required. There is enough information to make a diagnosis.

genetic testing

What is the primary genetic cause of Alport syndrome?
A
Mutation in COL4A5 gene
B
Mutation in COL4A4 gene
C
Mutation in COL4A3 gene
D
Mutation in COL4A6 gene

A
Mutation in COL4A5 gene

The COL4A5 gene mutation causes 85% of the cases of Alport syndrome.

Which of the following is a common symptom of Alport syndrome?
A
Joint pain
B
Hematuria
C
Skin rash
D
Vision loss

Hematuria

What type of hearing loss is associated with Alport syndrome?
A
Conductive hearing loss
B
Sensorineural deafness
C
Mixed hearing loss
D
Central auditory processing disorder

B
Sensorineural deafness

Which treatment is commonly used to slow the progression of kidney failure in Alport syndrome?
A
Corticosteroids
B
Antibiotics
C
ACE inhibitors
D
Diuretics

C
ACE inhibitors

ARBs can also be used.

What is a characteristic finding in a renal biopsy for Alport syndrome?
A
Basket weave appearance
B
Crescent formation
C
Thickening of the glomerular membrane
D
Glomerulosclerosis

A
Basket weave appearance

Discussion:

Learn More

Alport Syndrome

Cause and Manifestations

Alport syndrome is primarily caused by an X-linked genetic disorder resulting in a mutation in the gene encoding for type IV collagen, leading to abnormal basement membrane formation in the kidney, ears, and eyes. Clinical manifestations include progressive hereditary nephritis, sensorineural deafness, and eye abnormalities like cataracts.

Genetic Basis

Most common form is X-linked genetic mutation in COL4A5, which is more severe in men.

Other forms involve mutations in COL4A3C and COL4A4, affecting all genders equally.

Symptoms and Diagnosis

Common symptom is hematuria, which can be microscopic or macroscopic. Macroscopic hematuria is usually noted after exercise.

As kidney function declines, proteinuria may worsen.

Renal biopsy may reveal lamellation of the glomerular basement membrane and a basket weave appearance on electron microscopy.

Genetic testing can be performed to confirm the diagnosis.

Treatment and Management

ACE inhibitors and ARBs have shown potential in slowing kidney failure progression.

Treatments include dialysis and kidney transplant for kidney failure, and hearing aids for deafness.

Differential Diagnosis

Alport syndrome should be distinguished from thin basement membrane disease, IgA nephropathy, acute post-infectious glomerulonephritis, and polycystic kidney disease.

Inspiration: Alport Syndrome, National Library of Medicine

show less

Related:

Goal directed kidney therapy to decrease the progression of CKD with pillars of care effect revealed

Goal-Directed Kidney Therapy To Prevent Worsening Chronic Kidney Disease

Michael Aaronson

Lincoln Nephrology and Hypertension

CKD Stages Simplified – Patient Education by Michael Aaronson