Alport SyndromeHereditary Nephritis, Hemorrhagic Familial

Nephritis or Hereditary Deafness and Nephropathy

Prepared by:Dennis LagosKristian Pio PadillaLumier de JuanLara JoelenLyka Suansing

Causes, incidence and risk factorsAlport syndrome is an inherited disorder that

damages the tiny blood vessels in the kidneys. It is an inherited form of kidney inflammation (nephritis). It is caused by a mutation in a gene for a protein in the connective tissue, called collagen. These mutations come from  COL4A3, COL4A4, and COL4A5, collagen biosynthesis genes.

The disorder is uncommon. It most often affects males. Women can pass the gene for the disorder to their children, even if they have no symptoms. Risk factors include:End-stage kidney disease in male relativesFamily history of Alport syndromeHearing loss before age 30

SymptomsThe disorder damages the tiny blood vessels

in the glomeruli of the kidneys. The glomeruli filter blood to make urine and remove waste products from the blood.

At first, there are no symptoms. However, the destruction of the glomeruli over time leads to blood in the urine and may decrease the effectiveness of the kidney's filtering system. Often kidney function is lost over time and waste products and fluids build up in the body.

Symptoms include:Abnormal urine colorAnkle, feet and leg swellingBlood in the urineDecreased or loss of visionLoss of hearingSwelling around the eye

The condition can progress to end-stage renal disease at an early age.

Signs and TestsSigns include:

Changes to the eye, including the fundus, cataracts, or bulging of the lens.

High blood pressure.

The following tests may be done:AudiometryBUN and serum creatinineComplete blood countRenal biopsyUrinalysis

TreatmentsMonitoring blood pressure.Treating chronic kidney disease through

dialysis or kidney transplant.Surgery to repair cataracts.Hearing loss likely to be permanent.Genetic counseling.

Fechtner SyndromeA variation of Alport’s SyndromeIt is a rare condition characterized by the

presence of large blood platelets, kidney inflammation, deafness and abnormal leukocytes.

Results from a mutation in the MYH9 gene localized to 22q12-13, encodes the nonmuscle myosin heavy chain type IIA (MYHIIA), which is expressed in some blood cells (polynuclear cells, monocytes and platelets), in the cochlea and in the kidneys.

These molecular anomalies result in abnormal dimerization of the MYHIIA protein, which becomes unstable and coprecipitates with normal MYHIIA in the cytoplasm of leucocytes, thus forming cytoplasmic inclusion bodies.

This abnormal dimerization also leads to a failure to properly organize the cytoskeleton in megakaryocytes, which triggers macrocytic thrombopenia

Fig 3. Thin section of buffy coat sample fromperipheral blood of a patient with the Fechtnersyndrome. Many giant platelets. some larger than the two lymphocytes (LI are apparent in the sampIe(original magnification x 5.000; current magnification x 4000)

Giant platelet from another patient withFechtner syndrome. Although the cell is large. therelative numbers of granules (G). mitochondria (M).and dense bodies (DB) is not unusual. Microtubules(MT) and elements of the dense tubular system (DTS)of channels are present (original magnificationx26.500; current magnification x21.730).

SymptomsCongenital cataractsDeafnessNephritisEnlarged blood plateletsRenal diseaseIncreased protein levels in urineJuvenile glaucomaKidney diseaseExcessive menstrual bleedingThrombocytopeniaProteinuriaHematuria

Hemmorhagic Manifestationsthrombopenic purpuraEpistaxisprofuse menstruationsecchymoses