What is Alport syndrome?

From the Guidelines

Alport syndrome patients should be managed with a focus on slowing kidney disease progression through medications like ACE inhibitors or angiotensin receptor blockers, and genetic counseling is crucial for affected families. Alport syndrome is a genetic disorder affecting the kidneys, hearing, and eyes, caused by mutations in genes responsible for producing type IV collagen, a crucial component of basement membranes. The condition primarily leads to progressive kidney damage, resulting in hematuria (blood in urine), proteinuria (protein in urine), and eventually kidney failure. Management focuses on slowing kidney disease progression through medications like ACE inhibitors (such as enalapril 5-20 mg daily or lisinopril 10-40 mg daily) or angiotensin receptor blockers (such as losartan 25-100 mg daily), which reduce protein excretion and help preserve kidney function, as suggested by recent clinical practices 1. Blood pressure control is essential, typically aiming for levels below 130/80 mmHg. Regular monitoring of kidney function, hearing, and vision is necessary, with kidney function tests recommended every 3-6 months. As the disease progresses, patients may require dialysis or kidney transplantation. Genetic counseling is important for affected families since Alport syndrome follows different inheritance patterns (X-linked, autosomal recessive, or autosomal dominant) 1. The condition affects the inner ear and eyes as well, causing sensorineural hearing loss and various eye abnormalities, so regular audiometry and ophthalmologic examinations are recommended.

Some key points to consider in the management of Alport syndrome include:

• The use of genetic testing to identify presymptomatic genetic disease, although the benefits and harms of testing are still being debated 1
• The importance of establishing a unified disease terminology, including the use of two-part naming comprising both the clinical condition and gene name, to improve communication and precision in diagnosis and treatment 1
• The need for regular monitoring and follow-up to slow disease progression and improve quality of life for patients with Alport syndrome
• The potential risks and benefits of living donor kidney transplantation, including the increased risk of end-stage kidney disease in donors with a family history of Alport syndrome 1

From the Research

Definition and Characteristics of Alport Syndrome

• Alport syndrome is a genetic disorder that affects the basement membrane of the kidneys and can also impact other organs, such as the cochlea of the inner ear and eyes 2.
• It is characterized by mutations causing abnormalities in the collagen within the basement membrane, which has a crucial role in the filtration process of the kidneys 2, 3.
• The syndrome can manifest differently among individuals, and its severity can vary, with some people experiencing mild symptoms and others developing more severe kidney problems 2.

Clinical Manifestations and Diagnosis

• Alport syndrome is primarily characterized by kidney involvement, featuring persistent hematuria, proteinuria, and a progressive decline in renal function 4.
• Hearing loss, ocular abnormalities, and extrarenal manifestations further contribute to its complexity 3, 4.
• Diagnosis relies on urinalysis, histologic examination, and genetic testing, with advancements in next-generation sequencing aiding identification 4.

Inheritance Patterns and Genetics

• Alport syndrome can be transmitted as an X-linked, autosomal recessive, or autosomal dominant disorder 3, 5.
• The disease results from mutations in COL4A3, COL4A4, and COL4A5 genes, disrupting the formation of the α3-α4-α5 chain in the collagen IV network 4.
• Genotype-phenotype correlations are relatively evident, with distinct presentations in X-linked, autosomal recessive, and autosomal dominant cases 4.

Treatment and Management

• Treatment for Alport syndrome primarily focuses on managing its symptoms and complications, with regular monitoring of kidney function and blood pressure, along with medications to control hypertension 2.
• In cases of severe kidney damage, kidney transplantation may be necessary 2.
• Early diagnosis and intervention can improve outcomes and quality of life for individuals with Alport syndrome, emphasizing the importance of genetic testing for prognosis and familial screening 2, 4.