Identification of Sandhoff disease in a Thai family: clinical and biochemical characterization

Area of Science:

• Neurology
• Genetics
• Biochemistry

Background:

• Sandhoff disease is a rare lysosomal storage disorder, a type of GM2 gangliosidosis, affecting lipid metabolism.
• This condition results from mutations in the HEXB gene, leading to deficient beta-hexosaminidase B activity.
• Its prevalence is notably low in Thailand, making case reports significant for understanding regional epidemiology.

Observation:

• A Thai family presented with two children diagnosed with the infantile form of Sandhoff disease.
• The proband displayed an atypical early symptom: mitral valve prolapse with mitral regurgitation.
• Subsequent clinical manifestations included developmental regression, hypersensitivity to sound (startle reaction), and characteristic cherry-red spots in the macula.

Findings:

• Biochemical analysis confirmed the diagnosis of Sandhoff disease in both affected children.
• The early cardiac manifestation (mitral valve prolapse) is an uncommon presentation for this GM2 gangliosidosis.
• The clinical course followed a pattern of initial cardiac anomaly, followed by neurological deterioration.

Implications:

• This case highlights the importance of considering rare genetic disorders like Sandhoff disease even with atypical initial symptoms.
• Early identification of Sandhoff disease, potentially through cardiac screening in at-risk populations, could aid timely intervention.
• Understanding the varied clinical spectrum of Sandhoff disease is crucial for accurate diagnosis and management, particularly in underrepresented regions.