Tay-Sachs Disease: Autosomal Recessive Inheritance Explained

Inheritance Pattern

Tay-Sachs disease is an autosomal recessive disorder, not codominant.

Autosomal Recessive vs. Codominance

Feature	Autosomal Recessive (Tay-Sachs)	Codominance (e.g., ABO blood group)
Allele expression	Two mutant alleles needed for disease phenotype	Both alleles expressed in heterozygote
Heterozygote (carrier)	Asymptomatic (or mild biochemical phenotype)	Distinct, detectable phenotype (e.g., type AB blood)
Recurrence risk (carrier × carrier)	25% affected, 50% carrier, 25% unaffected	N/A (not a disease model)
Enzyme activity in carriers	~50% hexosaminidase A – usually sufficient	Both gene products functional

Tay-Sachs Specifics

• Gene: HEXA on chromosome 15q23-q24
• Deficiency: β-hexosaminidase A → GM2 ganglioside accumulation in neurons
• Forms: Infantile (classic, fatal by age 4–5), juvenile, late-onset (adult)
• Carrier frequency: ~1/27 Ashkenazi Jewish, 1/250 general population
• Screening: Enzyme assay + DNA analysis; recommended preconception/prenatal in high-risk groups.

Why Not Codominance?

Carriers do not express a distinct "intermediate" disease phenotype. The 50% enzyme level is typically asymptomatic, unlike codominant traits where both alleles produce visible, measurable products simultaneously (e.g., HbA and HbS in sickle cell trait – which is codominant at the molecular level).