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.


Krabbe disease (also called globoid cell leukodystrophy) is a severe neurological condition. It is part of a group of disorders known as leukodystrophies, which results from demyelination in the nervous system. Krabbe’s is a monogenic disorder caused by the mutation in the GALC gene and has an autosomal recessive inheritance¹ . The early-onset type of Krabbe disease is the most common and the most severe.Babies who have early-onset (infantile) Krabbe disease typically develop features in the first six months of life.Symptoms of infantile Krabbe disease may include irritability, failure to thrive, slowed development, and unexplained fevers.

These are followed by progressive muscle weakness, hearing and vision loss, and decreased movement. Symptoms of the later-onset types of Krabbe disease start in childhood, early adolescence, or adulthood. These may include muscle weakness & stiffness, loss of milestones, blindness, behavior problems, dementia, and seizures ².


A Female Baby Born Of Second-degree Consanguineous Marriage Of Age 5 Months Presented With:

  1. Regression of milestones (cognitive & motor)
  2. Visual impairment
  3. Muscle weakness
  4. Bulbar dysfunction
  5. Myoclonic jerks
  6. Brain MRI observed with periventricular hyperintensities, thalamic hypodensity, pyramidal trait

Tests Prescribed

  1. Enzyme Analysis for Beta Galactocerebrosidase
  2. Clinical Exome Sequencing

About the Prescribed Tests

Test Name Sample Type Method Description
Enzyme Analysis for Beta
2-4 ml Sodium Heparin Blood Fluorometry assay with artificial substrate Assay carried on leukocytes
Clinical Exome Sequencing 2-4 ml EDTA Blood Next Generation Sequencing Mean coverage of 80-100X coverage.
Target coverage 200X

Test Results

  1. Enzyme Analysis: Baby was found to have low Beta Galactocerebrosidase activity (0.08 nmol/17hr/mg) vs. biological reference range 4-40 nmol/17hr/mg).
  2. Clinical Exome Sequencing: In Exome data, homozygous deletion was suspected from Exon 11-17 in GALC gene. However, in order to confirm the results, an in-house PCR testing was performed, that confirmed the homozygous deletion.


  1. The recommended first-tier test for Krabbe disease is GALCW / Galactocerebrosidase, Leukocytes.
  2. Individuals with GALC activity below the reference range for these assays are more likely to have variants in the GALC gene that are identifiable by molecular genetic testing³.
  3. Variants of uncertain significance (VUS) also cause decreased GALC activity, hence these variants can be potentially disease causing if there is a decrease in GALC activity
  4. Exome sequencing along with enzyme activity analysis can significantly improve the diagnostic yield.

This bulletin is compiled by

Name Designation Contribution
Ms. Krishnendu Menon Manager-Scientific Affairs Compilation
Ms. Vineeta Singh Vice President-Scientific Affairs Exome Analysis
Ms. Divya Borkar Manager - Biochemical Genetics Enzyme Assay


  1. 1Medline Plus,https://medlineplus.g...Click here
  2. ²Rare Diseases,NIH,https://rarediseases....Click here
  3. ³Mayo Clinichttps://www.mayocliniclabs...Click here