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.


Mucopolysaccharidosis type III is a multisystem lyso-somal storage disorder characterized by progressive degeneration of the central nervous system. It is a rare genetic condition that causes fetal brain damage and is a type of childhood dementia. MPS III is caused due to lack of an enzyme that breaks down and recycles a complex sugar molecule called 'heparan sulfate' leading to the accumulation of this molecule in the cells of the central nervous system2. It is inherited is an autosomal recessive pattern. Children with MPS III usually appear healthy at birth. The symptoms first appear between the ages of 2 to 6 years, with behavioral disorders (hyperkinesia, aggressiveness) and intellectual deterioration, sleep disorders, and very mild dysmorphism.

The neurological involvement becomes more prominent around the age of 10 years with a loss of motor milestones and communication problems3. Other symptoms include coarse hair, excess hair growth (hirsutism), slightly coarse facial features, mildly enlarged liver and/or spleen, speech delay, respiratory and ear infections, diarrhea, hernias, sei- zures, and unsteady gait2. Children with MPS III also often experience hearing loss and vision impairment. It is a not yet treatable severe neurodegenerative disease, develop- ing new therapeutic strategies might change the course of the disease significantly.


A 6 years old female baby born to a consanguineous couple presented with:

  1. Mitral valve prolapse
  2. Moderate to Severe Mental Retardation
  3. Intellectual Disability
  4. Developmental and Speech delay.

Tests Prescribed

  1. Whole Exome Sequencing
  2. Enzyme Analysis of Alpha N-acetyl glucosaminidase

About the Prescribed Tests

Test Name Sample Type Method Description
Whole Exome Sequencing EDTA Blood Next Generation Sequencing Paired-End Sequencing was performed with 2x100/2x150 chemistry, on an Illumina platform.
Enzyme Analysis for Alpha N-acetyl glucosaminidase Sodium Heparin Blood Fluorometry assay with artificial substrate Assay carried on leukocytes.

Test Results

  1. Whole Exome Sequencing: Homozygous Likely pathogenic Variant in Exon1 in NAGLU gene associated with MPS Type III was detected. However, the variant has a low depth. Therefore, further testing by Enzyme analysis was recommended by the clinician.
  2. Enzyme Analysis: Individual was found to have low activity of Alpha N-acetyl Glucosaminidase (0.1 nmol/17hr/mg) vs. biological reference range (6-20 nmol/17hr/mg) which is consistent with the diagnosis of MPS Type III B (Sanfilippo Type B) disease.


  1. The recommended first-tier test for MPS Type III is Alpha N-acetyl glucosaminidase enzyme assay in leuko- cytes.
  2. Individuals found to have low activity of Alpha N-acetyl glucosaminidase enzyme than the normal range may be consistent with the diagnosis of MPS Type III disease. However, it is suggested to confirm the enzyme deficiency from cultured skin fibroblasts.
  3. Whole Exome Sequencing establishes the diagnosis of MPS III in a proband with suggestive clinical and lab- oratory findings in whom either biallelic pathogenic variants in one of four genes (GNS, HGSNAT, NAGLU, and SGSH) or deficiency of the respective lysosomal enzyme has been identified1.

This bulletin is compiled by

Name Designation Contribution
  Manager-Scientific Affairs Compilation
  HOD, Clinical Bioinformatics Exome Analysis
  Sr. Manager, Enzymology Enzyme Assay

Test Results

  1. Rare Diseases, click here
  2. OMIM, click here
  3. NCBI, https://www.ncbi.nlm... click here
  4. click here