Question

A child demonstrates progressive neurological decline and a cherry-red spot on fundus examination. Enzyme analysis reveals a deficiency in hexosaminidase A. What is the most likely diagnosis?

• A. GM1 gangliosidosis
• B. GM2 gangliosidosis
• C. Niemann--Pick disease
• D. Gaucher disease

Hint:

Hexosaminidase A deficiency + cherry-red spot + neurodegeneration = Tay--Sachs disease GM2 gangliosidosis.

Answer 1

The Correct Option is B

Step 1: Understanding the Question:
The combination of a "cherry-red spot" on the retina and a specific deficiency in hexosaminidase A defines a classic lysosomal storage disorder.
Step 2: Detailed Explanation:

Tay-Sachs Disease: This is the most common form of GM2 gangliosidosis. It is an autosomal recessive disorder caused by a mutation in the HEXA gene on chromosome 15, leading to a deficiency of the enzyme Hexosaminidase A.

Pathophysiology: Without Hexosaminidase A, the cell cannot break down GM2 gangliosides. These lipids accumulate progressively within the lysosomes of neurons, leading to massive neuronal swelling and degeneration.

Clinical Features: Affected infants usually appear normal until 3-6 months of age, followed by loss of motor skills (regression), exaggerated startle response to noise (hyperacusis), and macrocephaly. Progressive paralysis, seizures, and blindness follow.

The Cherry-Red Spot: The accumulation of gangliosides in the retinal ganglion cells causes the macula to appear white/pale. Because the fovea lacks ganglion cells but is thin, the underlying red choroid shows through, creating the "cherry-red spot" appearance.

Differential - Niemann-Pick: Type A also features a cherry-red spot but is caused by sphingomyelinase deficiency and presents with hepatosplenomegaly, which is ABSENT in Tay-Sachs.

Step 3: Final Answer:
Hexosaminidase A deficiency leads to the accumulation of GM2 gangliosides, causing GM2 gangliosidosis (Tay-Sachs disease).