Familial Global Developmental Delay Secondary to β-Mannosidosis

Area of Science:

• Genetics
• Biochemistry
• Pediatrics

Background:

• Beta-mannosidosis is a rare autosomal recessive lysosomal storage disorder.
• It results from deficient activity of the enzyme beta-mannosidase, encoded by the MANBA gene.
• This deficiency leads to the accumulation of mannose-containing oligosaccharides in lysosomes.

Observation:

• Two Indian siblings from a consanguineous marriage presented with global developmental delay in late infancy.
• Clinical findings included hypotonia in both siblings, with hepatosplenomegaly in one.
• Ophthalmological, audiological, and skeletal assessments were normal.

Findings:

• Enzyme assays confirmed the complete absence of beta-mannosidase activity.
• Next-generation sequencing identified a homozygous splice-site mutation (c.1317+1G>A) in intron 10 of the MANBA gene.
• Sanger sequencing validated this mutation in both siblings and identified heterozygous carriers in the parents.

Implications:

• This study identifies a novel mutation in the MANBA gene associated with beta-mannosidosis.
• It highlights the importance of genetic testing in diagnosing rare lysosomal storage disorders, especially in consanguineous populations.
• Understanding genotype-phenotype correlations in beta-mannosidosis can aid in clinical management and genetic counseling.