Question

A Jewish couple of Eastern European descent presents to the clinic for prenatal counseling after their only child died early in childhood. The family could not remember the name of the disorder but said it was common in their ancestry. Their first child was normal at birth, a slightly larger than normal head circumference, an abnormal “eye finding,” and a severe progressive neurologic disease with decreased motor skills and eventually death. The autopsy is consistent with Tay-Sachsdisease.

What type of inheritance is this disorder? What is the biochemical cause of the disorder?

Answer 1

Inheritance is autosomal recessive in this type of disorder and this disease happens when the patient inherits one mutation from each of their parents. It is caused by mutation in the HEXA gene which is located at long arm of chromosome 15 (which is an autosome i.e not sex chromosome).

HEXA gene is responsible for the production of an enzyme called beta-hexosaminidase A which helps in developing brain and spinal cord. This enzyme lives in lysosomes which are considered as the recycling center of the cell. Inside the lysosomes, GM2 ganglioside which is a type of fat is being broken by beta-hexosaminidase A. When mutation occurs, HEXA gene hinders beta-hexosaminidase A from breaking the fat and as a result this fat gets deposited and toxicity accumulates the neurons of brain and spinal cord creating much damage.