Hereditary β-mannosidosis in a dog: Clinicopathological and molecular genetic characterization

Pompei Bolfa, Ping Wang, Rajeev Nair, Sreekumari Rajeev, Anibal G. Armien, Paula S. Henthorn, Tim Wood, Mary Anna Thrall, Urs Giger

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Hereditary β-mannosidosis causing progressive lysosomal neuropathy and other clinical signs, has been previously described in humans, Nubian goats, and Salers cattle. Here we report the clinicopathological, metabolic, and molecular genetic features of canine beta-mannosidase (MANBA, EC deficiency. A 1-year-old male mix-breed dog from St. Kitts was presented with progressive stumbling, weakness, and regurgitation. Vacuolated lymphocytes were observed on the blood film. Postmortem findings included marked enlargement of nerves, megaesophagus, and internal hydrocephalus. Vacuolated macrophages, neurons, and secretory epithelial cells suggested an oligosaccharide storage disease. Plasma concentration of the β-mannosidosis specific oligosaccharide was approximately 75 fold that of controls. The plasma beta-mannosidase activity was severely reduced to ~5% of controls; five other lysosomal acid hydrolase activities were increased or within their normal reference interval. Genomic sequencing of this dog's MANBA gene identified a homozygous exonic five bp tandem duplication in the penultimate exon of the MANBA gene (c.2377_2381dupTATCA) which results in a reading frame shift, altering the subsequent amino acid sequence and creating a premature stop codon. The truncated beta-mannosidase enzyme is expected to be dysfunctional. This enzyme deficiency causes the accumulation of un-degraded oligosaccharides in cells, which affect the myelination of the peripheral and central nervous systems. This insertion was not encountered in 121 and 80-screened samples from dogs on St. Kitts (all were homozygous for wild-type) and Philadelphia region (wild-type), respectively. In conclusion, canine β-mannosidosis has similar clinicopathological features with some human patients, but milder signs than in ruminants and more severe than in knockout mice. Hence, dogs with β-mannosidosis could become a valuable disease model for the human disease.

Original languageEnglish (US)
Pages (from-to)137-143
Number of pages7
JournalMolecular Genetics and Metabolism
Issue number1-2
StatePublished - Sep 1 2019

Bibliographical note

Funding Information:
We thank David Hilchie for technical support with histopathology, Drs. Andrea Peda, Adam Silkworth, Sarah Cavanaugh, Ryan Cavanaugh, and Valeria Benitez for help with sample collection from dogs on St. Kitts. We are also grateful to Dr. Laura Pollard and Allison Cason, Biochemical Genetics Laboratory, Greenwood Genetic Center, for assistance in analysis of plasma oligosaccharides. Studies at the University of Pennsylvania were supported by a grant from the National Institutes of Health ( OD010939 ).

Publisher Copyright:
© 2019 Elsevier Inc.


  • Animal model
  • Canine
  • Inborn error of metabolism
  • Lysosomal storage disease
  • MANBA gene
  • Mutation


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