However apparent autosomal dominant transmission of disease associated with mutations in COL4A3 and COL4A4 does occur.Clinical utility gene card for: Alport syndrome. Diagnosis
The diagnosis can usually be made on a combination of clinical, family history, and biopsy criteria. Biopsy of kidneys or skin
To be helpful, kidney biopsies need to be taken before the disease is too advanced. Changes on conventional (light) microscopy are not characteristic, and the possibility of other diagnoses, particularly focal segmental glomerulosclerosis (FSGS), may be raised. Electron microscopy shows a characteristic sequence of changes from thinning of the glomerular basement membrane (GBM), developing into areas of thinning and thickening, and finally into a complex appearance with apparent splitting, often described as a basketweave appearance. Early or very localised changes on this spectrum are not diagnostic, but the later changes are considered diagnostic.Immunohistochemistry or immunofluorescence studies to identify the COL3-4-5 proteins in GBM can be helpful. However, these studies may be normal in some patients with Alport syndrome, especially milder variants.The skin contains type IV collagen in a 556 network. Skin biopsies have been used to show the absence of the COL4A5 gene product, but these techniques are not straightforward, only apply to patients with severe COL4A5 mutations, and are not widely available. Genetic testing is now a better alternative if kidney biopsy is not possible. Family history
A family history of end-stage renal disease with hearing impairment is suggestive of Alport syndrome, but other conditions can cause this combination of abnormalities. Most can be distinguished by clinical features.
Alport syndrome is a genetic disorder affecting around 1 in 5,000-10,000 children, characterized by glomerulonephritis, end-stage kidney disease, and hearing loss. 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. 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.). Depending on where the mutation is located in the genome, Alport syndrome can present itself in many forms. This includes X-linked Alport syndrome (XLAS), autosomal recessive Alport syndrome (ARAS), and autosomal dominant Alport syndrome (ADAS). Signs and symptoms
These descriptions refer to classic Alport syndrome, which usually causes significant disease from young adult or late childhood life. Some individuals, usually with milder mutations or carrier status, develop disease later, or show only some of the features of classic disease. Chronic kidney disease
Blood in urine is a usual feature of Alport syndrome from early infancy, identifiable on urine dipsticks.