Alport Syndrome, Causes, Signs and Symptoms, Diagnosis and Treatment.
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Chapters
0:00 Introduction
1:01 Causes of Alport Syndrome
4:06 Symptoms of Alport Syndrome
4:47 Diagnosis for Alport Syndrome
5:18 Treatment of Alport Syndrome
Alport syndrome is a genetic disorder[1] affecting around 1 in 5,000-10,000 children,[2] characterized by glomerulonephritis, end-stage kidney disease, and hearing loss.[3] Alport syndrome can also affect the eyes, though the changes do not usually affect vision, except when changes to the lens occur in later life. Blood in urine is universal. Proteinuria is a feature as kidney disease progresses.
The disorder was first identified in a British family by the physician Cecil A. Alport in 1927.[4][5] Alport syndrome once also had the label hereditary nephritis, but this is misleading as there are many other causes of hereditary kidney disease and 'nephritis'.
Alport syndrome is caused by an inherited defect in type IV collagen—a structural material that is needed for the normal function of different parts of the body. Since type IV collagen is found in the ears, eyes, and kidneys, this explains why Alport syndrome affects different seemingly unrelated parts of the body (ears, eyes, kidneys, etc.). These descriptions refer to 'classic' Alport syndrome, which usually causes significant disease from young adult or late childhood life.[6] Some individuals, usually with milder mutations or 'carrier' status, develop disease later, or show only some of the features of classic disease.[citation needed]
Chronic kidney disease
Blood in urine is a usual feature of Alport syndrome from early infancy, identifiable on urine dipsticks. In young children, episodes of visible (macroscopic) haematuria may occur. Protein begins to appear in urine as the disease progresses. This is now regarded as an indication for treatment with ACE inhibitors. Progressive loss of kidney function (reflected clinically by increases in serum creatinine or decreases in estimated glomerular filtration rate) can occur and may require treatment with renal replacement: dialysis or a kidney transplant.[7]
Hearing loss
Alport syndrome can also cause hearing loss although some patients are not affected.[8] Hearing in Alport syndrome patients is normal at birth. Hearing loss in affected patients develops progressively, usually at the stage when kidney function is normal, but there is substantial proteinuria. However, in some patients, hearing loss is only noted after kidney function has been lost. Characteristically the early changes are reduced ability to hear high-frequency sounds, 'sensory neural deafness'. This becomes more severe and affects lower frequencies too. Hearing loss is not usually complete in Alport syndrome; good communication is almost always possible with the use of hearing aids.[9]
Leiomyomatosis
Diffuse leiomyomatosis of the oesophagus and tracheobronchial tree has been reported in some families with Alport syndrome. Symptoms usually appear in late childhood and include dysphagia, postprandial vomiting, substernal or epigastric pain, recurrent bronchitis, dyspnea, cough, and stridor. Leiomyomatosis is confirmed by computed tomography (CT) scanning or magnetic resonance imaging (MRI).[10]
Eye changes
Various eye abnormalities are often seen including lenticonus, keratoconus, cataracts and corneal erosion as well as retinal flecks in the macula and mid-periphery.[11] These rarely threaten vision. Lenticonus (cone-shaped lens) can be treated by replacement of the lens, as for cataracts. Mild keratoconus can be managed with hard, scleral, piggy-back or other specialty medical contact lenses; progressive cases may be halted with corneal collagen cross linking; and severe cases may require a corneal transplant.[12] Macular abnormalities such as incomplete foveal hypoplasia or staircase foveopathy are common in Alport syndrome.[13]
It may also be associated with retinitis pigmentosa.[14]
Other abnormalities
Aortic dissection has been described very rarely in patients with early-onset disease.[6] Leiomyomas, tumours of smooth muscle affecting the oesophagus and female genital tract, may occur in a rare overlap syndrome involving the adjacent COL4A5 and COL4A6 genes.[15]
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