Welcome to the Rare Classroom, a new series from Patient Worthy. Rare Classroom is designed for the curious reader who wants to get informed on some of the rarest, most mysterious diseases and conditions. There are thousands of rare diseases out there, but only a very small number of them have viable treatments and regularly make the news. This series is an opportunity to learn the basics about some of the diseases that almost no one hears much about or that we otherwise haven’t been able to report on very often.

Eyes front and ears open. Class is now in session.

The rare disease that we will be learning about today is:

Alport Syndrome

What is Alport Syndrome?

• Alport syndrome is a genetic disorder characterized by hearing loss, glomerulonephritis, and progressive, chronic kidney disease
• Once labeled “hereditary nephritis,” this term is misleading because there are other hereditary disorders that can lead to nephritis
• There are multiple forms of Alport syndrome that appear depending on where the causal genetic mutation occurs:
  • Autosomal dominant Alport syndrome
  • Autosomal recessive Alport syndrome
  • X-linked Alport syndrome
• Alport syndrome is named after Cecil A. Alport, a physician that first described the disorder in an English family in 1927

How Do You Get It?

• Alport syndrome is a genetic disorder and is the result of genetic mutations
  • Genes that may be mutated in Alport syndrome include COL4A3, COL4A4, COL4A5
  • The mutations inhibit the normal production of type IV collagen
    • This collagen is a critical aspect of the basement membrane of the eye, inner ear, and kidneys, among other places/organs
• In about 85 percent of cases, Alport syndrome is inherited in an X-linked pattern; this form is attributed to the COL4A5 mutation
• The autosomal dominant form is often now classified as different conditions
• The autosomal recessive form is attributed to COL4A3 and COL4A4; genes are located on chromosome 2 and both copies must be mutated

What Are the Symptoms?

• Symptoms of Alport syndrome can include:
  • Chronic kidney disease
    • Blood in the urine
    • Protein in the urine
    • Progressive loss of kidney function, eventually leading to end-stage kidney disease and kidney failure
  • Hearing loss
    • Hearing loss is possible in Alport syndrome, but some patients aren’t affected
    • Usually, the hearing impediment does not progress to complete deafness
    • Symptoms usually begin before kidney function decline and around the beginning of proteinuria (protein in urine)
  • Vision changes
    • Eye abnormalities include:
      • Keratoconus
      • Lenticonus
      • Corneal erosion
      • Cataracts
      • Retinal flecks
      • Retinitis pigmentosa (more rarely)
  • Leiomyomatosis
    • Epigastric pain
    • Recurrent bronchitis
    • Dysphagia
    • Coughing
    • Dyspnea
  • Aortic dissection and leiomyomas (a smooth muscle tumor affecting the female genitalia and esophagus) are less commonly reported

How Is It Treated?

• Kidney Disease
  • ACE inhibitors appear effective in slowing the progression of kidney disease in Alport syndrome
    • Treatment typically begins once proteinuria appears
  • As the kidneys fail, transplant or dialysis is required
  • Gene therapy has been discussed as a potential future treatment
• Hearing loss can be effectively managed using hearing aids
  • They are often needed by the teen or young adult years
• Treatments for eye problems may include specialty contact lenses, corneal collagen cross linking, or corneal transplant

Where Can I Learn More???

• Learn more about this disease from the Alport Syndrome Foundation.
• Check out our cornerstone on this disease here.