Alport Syndrome or Hereditary Nephritis: Definition, Causes, Risk Factors, Symptoms, Diagnosis, Treatment
Alport Syndrome or Hereditary Nephritis is a genetic disorder of kidney that often causes significant kidney malfunction. Hereditary Nephritis is quite rare. Gender wise, it usually affects the male population. Females are often asymptomatic and pass on the abnormal genes to their male or female offspring. The symptoms are observed in mostly male offspring.
In this article, we will discuss about the various causes, genetic abnormalities and symptoms of Alport Syndrome or Hereditary Nephritis.
How Is Alport Syndrome or Hereditary Nephritis Defined?
- Alport Syndrome or Hereditary Nephritis is a hereditary genetic disease.
- The clinical manifestations of syndrome are characterized by glomerulonephritis, end stage renal disease, abnormal vision and acute hearing loss.
- In most cases urine examination suggests presence of blood in urine also known as hematuria.
What Causes Alport Syndrome or Hereditary Nephritis?
- Alport Syndrome or Hereditary Nephritis is a hereditary disease caused by genetic mutations.
- Hereditary Nephritis is usually caused by mutations of genes in COL4-A3, COL4-A4, and COL4-A5.1
- These genes are involved in biosynthesis of collagens.
- Mutations in any of the above-mentioned genes hamper appropriate production of type IV collagen network.2
- The Type IV Collagen Network is a vital component of basement membranes in kidneys, inner portion of the ear, and the eyes.
- The basement membranes are extremely thin sheet type structures whose function is to separate and support cells in many tissues.
- When the formation of type IV collagen fibers is hampered due to gene mutations, the basement membranes of kidneys cannot filter the waste products from blood and create urine in a normal fashion, hence allowing even blood and protein to pass through urine.
Abnormalities of Basement Membrane
- Collagen abnormalities associated with Alport Syndrome causes abnormalities of the basement membrane in kidney tissue.
- Abnormal deposition of collagen in basement membrane within kidney tissues causes progressive scarring.
- Multiple scarring of kidney tissue results in renal failure.
- As the disease progresses, the basement membrane gets thickened.
- When a computational study of a solitary molecule of type IV collagen is conducted, it reveals changes in the structure of the mutated molecules.
Risk Factors for Alport Syndrome or Hereditary Nephritis
- End stage renal disease, especially in males
- There is a family history of Alport Syndrome or Hereditary Nephritis
- Acute hearing loss before the age of 35
Symptoms of Alport Syndrome or Hereditary Nephritis
- Age 30 years or less- No symptoms.
- Microscopic Hematuria- Observed when urine examination is done during annual physical examination.
Later Or Advanced Stage Of The Disease-
- Frank Hematuria-
- Abnormal color of urine observed by patient.
- Microscopic Hematuria-
- Hematuria is often not observed in female patients.
- Edema Feet-
- Swelling of the lower extremities
- Impaired Vision
- Lens of the eye protrudes in anterior chamber resulting in vision abnormalities
- Seen in 1/5th of the patient with history of Alport Syndrome.
- Pain in the Flank-
- Rare in early stage but common in late stage.
- Hearing Loss
- Bilateral sensorineural hearing loss is a characteristic feature.
- Hearing loss is caused by adhesion of the auditory sensory cells to the basilar membrane of the inner ear.
- End Stage Renal Disease (ESRD)- Alport Syndrome or Hereditary Nephritis gradually progresses to end stage renal disease in male patient at a relatively young age between 30 and 40 years of age.
Diagnosis of Alport Syndrome or Hereditary Nephritis
Tests To Diagnose Alport Syndrome or Hereditary Nephritis:
- Personal or Family History- 3 symptoms like hematuria, visual abnormalities and hearing loss.
- Urine Analysis- Hematuria or blood in urine.
- Audiometry Testing- Test indicates hearing loss.
- Blood Examination- Increase BUN and creatinine, low hemoglobin and lower count of red blood cells.
- Biopsy of the Kidney- Structural abnormalities of basement and glomeruli confirms the diagnosis.
- Skin Biopsy- Skin biopsy is much simple test than kidney biopsy.
- Molecular Genetic Testing- Reliable test but expensive and not available in all hospitals or labs.
Treatment for Alport Syndrome or Hereditary Nephritis
The main aim of treatment is to monitor and control the disorder and treatment of the symptoms.
- Treat Proteinuria- Angiotensin Blockade- Reduces protein excretion from renal tubule.
- Hypertension in ESRD- Responds to angiotensin treatment
- Dialysis- ESRD is treated with dialysis until patient is qualified for kidney transplant.3
- Kidney Transplant- Mostly suggested for bilateral end stage renal disease
Prognosis of Alport Syndrome or Hereditary Nephritis
- Female Patients- The female population with Alport Syndrome or Hereditary Nephritis usually has a relatively normal life with a very few symptoms.
- Male Patients- On the contrary male population develops several complications associated with Alport Syndrome.
- Complications- Vision abnormalities and hearing loss are more often seen with male patients. End stage renal disease likely begins by the time the individual is 50 years of age.
- Chronic Renal Failure- Causes hematuria, proteinuria and hypertension. All three symptoms are treated for symptomatic relief.
- End Stage Renal Disease (ESRD)-
- Most of the male patients in late stage develop ESRD.
- 90% of Male patient of Alport Syndrome above 40 years develop signs of ESRD.
- ESRD in patients with minor mutation is rare before age 40 years.
- Mutation of Gene COL4A5 causes early development of ESRD in 90% of male patients.
- Permanent Deafness
- Vision Impairment
1. X-linked, COL4A5 hypomorphic Alport mutations such as G624D and P628L may only exhibit thin basement membrane nephropathy with microhematuria and late onset kidney failure.
Pierides A1, Voskarides K2, Kkolou M3, Hadjigavriel M3, Deltas C2.
Hippokratia. 2013 Jul;17(3):207-213.
2. Glomerular pathology in Alport syndrome: a molecular perspective.
Cosgrove D., Pediatr Nephrol. 2012 Jun;27(6):885-90. doi: 10.1007/s00467-011-1868-z. Epub 2011 Apr 1.
3. Encapsulating peritoneal sclerosis in a patient with Alport's syndrome on long-term peritoneal dialysis.
Bahcebasi ZB1, Akarsu O, Yildirim M, Kucuk H2. Saudi J Kidney Dis Transpl. 2014 Mar;25(2):419-22.