History and exam

Key diagnostic factors

common

gross hematuria

A common symptom, often precipitated by an intercurrent infection in a young child.

hearing impairment

Complications such as renal failure and deafness are typically more common in young males with X-linked Alport syndrome, but affect males and females equally with the autosomal forms.[4][7][36][37]

Other diagnostic factors

common

fatigue

Vague symptom related to the development of renal failure. May be due to anemia. Complications such as renal failure and deafness are typically more common in young males with X-linked Alport syndrome, but affect males and females with autosomal forms.[4][7][36][37]

breathlessness

Vague symptom related to the development of renal failure. Complications such as renal failure and deafness are typically more common in young males with X-linked Alport syndrome, but affect males and females with autosomal forms.[4][7][36][37]

peripheral edema

Vague symptom related to the development of renal failure or nephrotic syndrome. May result from impaired renal salt excretion. Complications such as renal failure and deafness are typically more common in young males with X-linked Alport syndrome, but equally affect males and females with autosomal forms.[4][7][36][37]

hypertension

Sign of chronic kidney disease.

foamy-appearing urine

Indicates proteinuria.

uncommon

visual disturbance

Often due to cataracts or corneal erosions. Cataracts may be a presenting symptom.[15]

learning disability

Associated with Alport syndrome with learning disability.

leiomyoma

Diffuse leiomyomatosis is a rare association with X-linked Alport syndrome due to a contiguous gene deletion involving the adjacent ends of the COL4A5 and COL4A6 genes.[38]​ Deletions are of variable size but the COL4A6 breakpoint is invariably in the second intron. Leiomyomas typically occur in the esophagus but may also be found in the respiratory tract and the female genital tract. Symptoms may occur at any age and will depend on the site of the leiomyomas. They include dysphagia, recurrent bronchitis, cough, genital or pelvic masses, and menorrhagia.

faltering growth

Sign of chronic kidney disease.

Risk factors

strong

family history of Alport syndrome

Family history will identify those members at risk of inheriting the condition, who should be offered screening, and in most cases will clarify the mode of inheritance. This may lead to earlier diagnosis and detection of complications such as hypertension. It may also allow the opportunity to consider prenatal diagnosis.

weak

family history of thin basement membrane nephropathy

Thin basement membrane nephropathy may be seen in up to 20% of cases of X-linked Alport syndrome and is also a manifestation of the carrier status of autosomal-recessive Alport syndrome (ARAS) due to mutations in the COL4A3 and COL4A4 genes.[20] Unless there is a family history of consanguinity, the risk of having children with ARAS for someone with thin basement membrane disease is low (around 1:400), as the population carrier frequency is low (≤1%). However, simple screening with urinalysis can be offered to partners of patients with, or suspected of having, thin basement membrane nephropathy.

family history of microscopic hematuria

Most likely found in the mother of males with X-linked Alport syndrome (XLAS) (father will be negative). All daughters of a man with XLAS will eventually manifest hematuria. Only about 50% of carriers of autosomal-recessive Alport syndrome will have hematuria and may be completely asymptomatic. However, there are other causes of familial hematuria such as familial IgA disease and other types of familial glomerulonephritis.

microscopic hematuria

Alport syndrome is an uncommon cause of microscopic hematuria with or without proteinuria. However, features of Alport syndrome and a family history should be sought in all patients with undiagnosed microscopic hematuria. About 10% of cases of X-linked Alport syndrome are due to new mutations so there is no family history.

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