**Question:** The earliest manifestation of Alkaptonuria is -

A. Joint pain
B. Skin discoloration
C. Muscle weakness
D. Chest pain

**Core Concept:** Alkaptonuria is a rare autosomal recessive genetic disorder characterized by the deficiency of the enzyme homogentisate 1,2-dioxygenase, which leads to the accumulation of homogentisic acid in the body. This results in the production of dark brown pigments called ochronosis.

**Why the Correct Answer is Right:** The earliest manifestation of Alkaptonuria is usually skin discoloration (option B). This occurs due to the deposition of ochronotic pigments in the skin, causing dark brown or black discoloration, particularly in areas exposed to sunlight, such as the joints, ears, and sclera of the eyes.

**Why Each Wrong Option is Incorrect:**

A. Joint pain (option A) can be a later manifestation of Alkaptonuria, often caused by ochronotic arthritis.

C. Muscle weakness (option C) is not usually the initial symptom but may develop later due to the involvement of muscles in ochronosis.

D. Chest pain (option D) is not a common initial symptom of Alkaptonuria, as it is primarily a skin and joint disease.

**Clinical Pearl:** Alkaptonuria is a rare disease, and its early diagnosis is crucial for preventing the progression of ochronosis and minimizing the risk of ochronotic arthropathy. Early diagnosis involves screening newborns or family members of affected individuals and can be done through genetic testing.

**Correct Answer:** B. Skin discoloration