A 1-year-old boy presents with a delay in motor development. Progressive muscle weakness and blindness ensue, and the patient dies within a year. The brain at autopsy shows swollen neurons that contain numerous lysosomes filled with lipid. Which of the following is the most likely diagnosis?
Tay-Sachs disease is a lethal, autosomal recessive disorder caused by an inborn deficiency of hexosaminidase A, which permits the accumulation of ganglioside GM1 in CNS neurons. The disease is fatal in infancy and early childhood. Retinal involvement increases macular transparency and is responsible for a cherry-red spot in the macula. On histologic examination, lipid droplets are seen in the cytoplasm of distended nerve cells of the CNS and peripheral nervous system. Electron microscopy reveals the lipid within lysosomes in the form of whorled "myelin figures." Swollen neurons that exhibit marked vacuolization of the perikaryon and contain lysosomes filled with lipid can also occur in other lipid-storage diseases (e.g., Gaucher disease, Niemann-Pick disease). The other diseases do not produce such neuronal changes.Diagnosis: Tay-Sachs disease
AL amyloidosis
Hurler syndrome
Phenylketonuria
Tay-Sachs disease
Central Nervous System