PEDBASE.org - The Pediatric Database - Detailed information of ALPORT SYNDROME

ALPORT SYNDROME

DEFINITION:

A familial nephritis characterized by hematuria, progressive renal failure, neurosensory hearing loss, and ocular abnormalities.

EPIDEMIOLOGY:

incidence: ?
- accounts for 3% of chronic renal failure in childhood
- most common of several types of hereditary nephritis
age of onset:
- childhood
risk factors:
- familial - autosomal dominant and x-linked variants
  - chrom.#: Xq22
  - gene: type IV collagen alpha 5 chain (COL4A5)
  - up to 20% have no family history (high spontaneous mutation rate)

PATHOGENESIS:

1. Background

Alport Syndrome results in a secondary glomerulopathy and tubulointerstitial dysfunction

2. Genetic Defect

genetic defect -> altered type IV collagen alpha 5 chain gene (COL4A5) -> renal, ocular, and auditory manifestations - one point mutation in exon 3 (cys -> ser) may interfere with the conformation of the noncollagenous domain of COL4A5 resulting in an unstable triple-helix formation

CLINICAL FEATURES:

1. Renal Manifestations

1. Hematuria

persistent or recurrent microscopic or gross

2. Proteinuria

can progress to the nephrotic level

3. Complications

Nephritic Syndrome (edema, hypertension, azotemia, oliguria)
Nephrotic Syndrome (edema, hypoalbuminemia, hyperlipidemia)
Chronic Renal Failure (CRF)

2. Auditory Manifestations

1. Sensorineuronal Hearing Loss

in 30% of patients, starts by age 10
neurosensory (high frequency -> speech -> deaf)

3. Ocular Manifestations

in 10-15% of patients
nystagmus
cornea - keratoconus (conical cornea)
lens - cataracts, microspherophakia, posterior or anterior lenticonus

INVESTIGATIONS:

1. Urinalysis

hematuria, proteinuria (minimum -> nephrotic)
microscope - glomerular pattern - damaged RBC's & RBC casts

2. Serum

hyperprolinemia, thrombocytopenia
normal complement

3. Renal Biopsy

LM - mesangial cell proliferation and capillary wall thick-ening -> progressive glomerular sclerosis -> tubulo-interstitial changes
EM - glomerular basement membrane changes (splitting of lamina densa, reduplication, lamellation, attenuation)
IFM - negative

MANAGEMENT:

1. Supportive

no treatment for underlying disorder
multidisciplinary approach
- Paediatrics, Nephrology, Ophthalmology, Audiology

2. Medical

medical management of complications:

1. Nephritic Syndrome

fluid restriction, control hypertension, manage hyperkalemia, manage pulmonary edema

2. Nephrotic Syndrome

fluid restriction, salt-free diet, diuretics, albumin transfusion, Prednisone, alkylating agents
see file on "Idiopathic Nephrotic Syndrome"

3. Chronic Renal Failure

dialysis, kidney transplant

3. Prognosis

1. Males

CRF in 2nd or 3rd decade -> dialysis/transplant
hearing loss

2. Females

normal life span and subclinical hearing loss
hematuria only upon stress or pregnancy

Pediatric Database - ALPORT SYNDROME

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