Tay-Sachs disease (TSD) is a rare inherited disorder in children caused by deficiency of the enzyme HEXA, leading to toxic buildup in nerve cells and progressive neurological decline.

Its infantile form typically manifests between 3 and 6 months of age with initial normal development followed by gradual loss of motor skills, muscle weakness, and an exaggerated startle response.

Genetic Mechanism and Pathogenesis

Tay-Sachs disease is inherited in an autosomal recessive pattern. Mutations in the HEXA gene cause near-complete or complete absence of hexosaminidase A enzyme activity. This enzymatic deficiency prevents proper degradation of GM2 gangliosides, a type of lipid, resulting in their toxic accumulation primarily in neurons and leading to progressive neurodegeneration.

The extensive neuronal damage disrupts developmental milestones and neurological functions critical to a child's growth.

Clinical Presentation in Children

The infantile form of Tay-Sachs disease is most common and rapidly progressive. Initial symptoms include:

- Loss of newly acquired motor skills such as turning over, sitting, and crawling.

- Muscle hypotonia progressing to spasticity and paralysis.

- Exaggerated startle reflex to sudden noises or stimuli.

- Visual impairment with characteristic cherry-red macular spots.

- Myoclonic jerks (involuntary muscle twitching).

- Seizures and cognitive decline.

Children become increasingly unresponsive and lose the ability to communicate or interact with their environment. By 2 to 5 years, life-threatening complications such as respiratory failure commonly arise. Less commonly, juvenile and adult-onset forms present with slower progression and milder symptoms, including clumsiness, loss of coordination, speech difficulties, and psychiatric symptoms, but these are rare in pediatric populations.

Diagnostic Approach

Diagnosis combines clinical evaluation with biochemical and genetic testing:

- Enzyme assay reveals markedly reduced or absent hexosaminidase A activity in blood or tissue samples. Infantile cases often show activity levels below 5% of normal.

- Genetic testing confirms mutations in the HEXA gene, enabling carrier detection and prenatal diagnosis.

- Ophthalmologic examination identifies the cherry-red spot, a distinctive but not exclusive finding.

- Neurological assessment documents hypotonia, hyperreflexia, and developmental regression.

Current Management and Research

No curative treatment exists for infantile Tay-Sachs disease. Care focuses on symptomatic and supportive management, including seizure control, nutritional support, and prevention of complications. Advances in gene therapy and enzyme replacement are in experimental stages, offering hope for future interventions.

Multidisciplinary care teams are vital to optimize quality of life, providing physical therapy, palliative care, and psychosocial support for families coping with the progressive nature of the disease.

Dr. Richard G. Boles, an authority in pediatric neurogenetics, states, "Understanding the underlying genetic and enzymatic defect in Tay-Sachs disease has paved the way for targeted diagnostic approaches and novel therapeutic research, although effective treatments for the infantile form remain elusive."

Tay-Sachs disease in children, predominantly in its infantile form, is a severe neurodegenerative genetic disorder caused by HEXA gene mutations leading to hexosaminidase A deficiency. It manifests during early infancy with motor regression, neurological deterioration, and characteristic retinal changes. Ongoing research into gene therapy offers future promise.

Heightened awareness and multidisciplinary management remain the cornerstone of care to support affected children and families through this challenging condition.