A 30 year old female presents with bluish black discoloration of sclera and pinna for last 4 months. Her urine turns black on standing. Which of the following enzyme is most likely to be deficient?
**Core Concept**
The patient's presentation is suggestive of alkaptonuria, a rare genetic disorder characterized by the accumulation of homogentisic acid in the body due to a deficiency of homogentisate 1,2-dioxygenase (HGD) enzyme.
**Why the Correct Answer is Right**
The HGD enzyme is responsible for breaking down the amino acids tyrosine and phenylalanine. In alkaptonuria, the deficiency of this enzyme leads to the accumulation of homogentisic acid, which is then oxidized to benzoquinone acetic acid, resulting in the characteristic bluish-black discoloration of the sclera and pinna, as well as the darkening of urine on standing. This pathophysiological process is a classic example of an inborn error of metabolism.
**Why Each Wrong Option is Incorrect**
* **Option A:** Glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with hemolytic anemia, particularly in response to oxidative stress, but it does not cause alkaptonuria.
* **Option B:** Phenylalanine hydroxylase deficiency leads to phenylketonuria (PKU), a different inborn error of metabolism characterized by elevated levels of phenylalanine in the blood.
* **Option D:** Tyrosinase deficiency is associated with oculocutaneous albinism type 1, a condition characterized by reduced pigmentation of the skin, hair, and eyes.
**Clinical Pearl / High-Yield Fact**
Alkaptonuria is a rare genetic disorder that can lead to significant morbidity, including ochronosis (bluish-black pigmentation of connective tissues), joint pain, and kidney stones. Early diagnosis and management can help prevent or delay the onset of these complications.
**Correct Answer:** C. Homogentisate 1,2-dioxygenase (HGD) enzyme.