A Sandor Initiative Towards Richer Clinical Insights
Disclaimer: This newsletter is intended to enrich the insights related to genetic disorders from a laboratory perspective. The objective of this newsletter is to share knowledge from a lab perspective to facilitate the dialogue of genetic disorders diagnosis. We want to sincerely thank the physicians whose dedication, knowledge and intelligence helps arrive at answers through diagnosis enabling timely and effective prevention.
Tay-Sachs disease is a rare, inherited neurodegenera-tive disease. People with Tay-Sachs disease do not have enough of an enzyme called beta-hexosamini-dase A1.The severity of expression and the age at onset of Tay-Sachs varies from infantile and juvenile forms that exhibit paralysis, dementia, blindness and early death to a chronic adult form that exhibits neuron dysfunction and psychosis.
In the general population, the carrier rate for
Tay-Sachs disease is approximately 1 in 250-300
people.Tay-Sachs is an autosomal recessive disease
caused by mutations in both alleles of a gene (HEXA)
on chromosome 15. HEXA codes for the alpha subunit
of the enzyme β-hexosaminidase A.
This enzyme is found in lysosomes, organelles that break down large molecules for recycling by the cell2.
The diagnosis of Tay-Sachs disease involves a
blood test that detects absent or very low levels of
beta-hexosaminidase A enzyme activity3. Molecu-
lar genetic testing of the HEXA gene may be used to
identify the specific mutations present, or to rule out
the disease if a false-positive blood test result is sus-
pected.
Treatment options aim to control some of the symp-
toms. For example, your provider may prescribe
medication to control seizures. Other treatment
measures include providing proper nutrition and hy-
dration.
A 5-months male child born of non-consanguineous marriage presented with:
Facial Dysmorphism: Dolichocephaly,Retrognathia, Broad Nasal Bridge.
MRI (3T) | MRS | ENMG + NCS + RNS |
---|---|---|
Gliosis along left inferior temporal gyrus, mild thinning of the cortex | Normal study | Patchy myopathic process involving proximal upper limb and tongue |
Test Name | Sample Type | Method | Description |
---|---|---|---|
Whole Exome Sequencing | 2-4 EDTA Blood | Next Generation Sequencing | Mean coverage of 80-100X coverage. Target coverage 200X |
Enzyme Assay | 2-4 EDTA Blood | Fluorometry assay | Enzyme Analysis of Beta Hexosaminidase A by fluorometry assay with artificial substrate |
Table 1. Whole Exome Sequencing result
TGene & Transcript | Variant | Location | Zygosity | Disorder (OMIM) | Inheritance | Classification |
---|---|---|---|---|---|---|
CACNA1G | c.164G>A(p.Ala550Thr) | Exon 8 | Heterozygous | Spinocerebellar ataxia 42, early-onset, severe, with neurodevelopmental deficits | Autosomal Dominant | VOUS |
HEX4 | c.134A>C(p.Gln45Pro) | Exon 1 | Homozygous | GM2-gangliosidosis, several forms; Tay-Sachs disease | Autosomal Recessive | VOUS |
MORC2 | c.598A>G(p.lie200val) | Exon 8 | Heterozygous | Charcot-Marie-Tooth disease, axonal, type 2Z;cancer |
Table 2. Enzyme Assay results
Test (Units) | Disorder | Results | Reference | Status |
---|---|---|---|---|
Beta Hexosaminidase A (nmol/hr/mg) | Tay-Sachs | 14.8 | 62-310 | Low |
Beta Galactosidase (nmol/hr/mg) | GM1-gangliosidosis | 141.0 | 70-324 | Normal |
Result Interpretation:- Low enzyme activity of ß-Hexosaminidase A in leukocytes may be consistent with the diagnosis of Tay-Sachs disease. (Table.2)
Name | Designation | Contribution |
---|---|---|
Mr. Nadir Aman | Genetic Counselor | Compilation |
Ms. Vineeta Singh | Vice President-Scientific Affairs | Exome Analysis |
Ms. Divya Borkar | Manager - Biochemical Genetics | Enzyme Assay |
References: