**Question:** First manifestation of Alport syndrome is -

A. Hematuria
B. Kidney stones
C. Otorrhea
D. Hearing loss

**Correct Answer:**

**Core Concept:**
Alport syndrome is a genetic disorder characterized by progressive kidney disease, hearing loss, and eye abnormalities. It is caused by mutations in COL4A3, COL4A4, or COL4A5 genes, which encode for type IV collagen alpha chains. These mutations lead to the absence or abnormal deposition of type IV collagen in the basement membranes of the kidneys, eyes, and inner ear.

**Why the Correct Answer is Right:**
The correct answer, hematuria, is the initial manifestation of Alport syndrome. Hematuria occurs due to the abnormal deposition of type IV collagen in the basement membranes of the kidneys, leading to damage and rupture of the glomerular capillaries. As the disease progresses, it can lead to proteinuria, hypertension, and eventually end-stage renal disease (ESRD).

**Why Each Wrong Option is Incorrect:**

A. Kidney stones: Although kidney stones can develop in Alport syndrome due to chronic kidney disease, they are not the initial manifestation of the disease.

B. Hearing loss: While hearing loss is a common manifestation of Alport syndrome, it is usually present later in the disease course, after hematuria and proteinuria have developed.

C. Otorrhea: Otorrhea, or ear discharge, is not a typical initial manifestation of Alport syndrome. It is more commonly associated with infections or other conditions affecting the ear.

**Clinical Pearl:**
Hematuria is a crucial aspect to recognize in clinical practice because it can lead to a suspicion of Alport syndrome, which should prompt further evaluation and genetic testing. Early diagnosis and management can prevent the progression to end-stage renal disease and its associated complications.