**Question:** Refsum's disease is due to deficiency of which of the following enzyme?

A. Vitamin B12
B. Lactase
C. Phosphatidylcholine esterase
D. Alpha-galactosidase

**Core Concept:**
Refsum's disease is a rare autosomal-recessive disorder characterized by the accumulation of unsaturated fatty acids, particularly hexanoyl-CoA, in various tissues and organs due to the deficiency of specific enzymes. In this case, we are focusing on the enzyme deficiency causing the disease.

**Why the Correct Answer is Right:**
Refsum's disease is caused by the deficiency of Phosphatidylcholine Esterase (PCHE), an enzyme involved in the degradation of phosphatidylcholine (PC) to choline and glycerol. This deficiency results in the accumulation of phosphatidylcholine derivatives like lyso-PC, lyso-PE, and lysophosphatidylcholine (LPC) in various tissues and organs, leading to the disease symptoms.

**Why Each Wrong Option is Incorrect:**

A. Vitamin B12 deficiency is not related to Refsum's disease. Vitamin B12 deficiency primarily causes neurological symptoms, while Refsum's disease affects the peripheral nervous system, retina, and other tissues.

B. Lactase deficiency is responsible for lactose intolerance, not Refsum's disease. Lactase is an enzyme that breaks down lactose in the small intestine, while Refsum's disease is a lipid storage disease.

C. Alpha-galactosidase deficiency is associated with Glycogen storage disease type III, also known as McLeod syndrome, rather than Refsum's disease. Alpha-galactosidase A deficiency leads to glycogen accumulation in various tissues, causing muscle weakness, joint pain, and other symptoms.

D. Alpha-galactosidase B deficiency is not related to Refsum's disease. Refsum's disease is caused by Phosphatidylcholine Esterase deficiency, while Alpha-galactosidase B deficiency is linked to Krabbe disease, affecting the central nervous system and causing demyelination.

**Clinical Pearl:**
Refsum's disease is a rare autosomal-recessive disorder affecting multiple organs and tissues due to the accumulation of unsaturated fatty acids and their derivatives. The underlying cause is the deficiency of Phosphatidylcholine Esterase (PCHE), an enzyme that plays a crucial role in the degradation of phosphatidylcholine (PC) to choline and glycerol. This deficiency leads to the accumulation of phosphatidylcholine derivatives like lyso-PC, lyso-PE, and lyso-PI in various tissues and organs, causing the characteristic symptoms of Refsum's disease.