ASPG and Aspartylglucosaminuria

ASPG has been robustly implicated in aspartylglucosaminuria, a lysosomal storage disorder, through multiple lines of genetic evidence. Case report data identified compound heterozygous missense mutations in two Canadian siblings, with one allele resulting from a G299>A transition (leading to a Gly100→Gln substitution) and the other from a T404>C transition (resulting in a Phe135→Ser change) (PMID:9137882). Further, a multi‐patient study has expanded the mutation spectrum by reporting a total of 10 distinct ASPG mutations in non‑Finnish populations, including the variant c.488T>C (p.Met163Thr) detected in unrelated individuals, thereby reinforcing autosomal recessive segregation and genetic heterogeneity (PMID:1722323).

The integration of these independent studies demonstrates strong concordance between clinical observations and genetic findings. Although direct functional studies linking ASPG dysfunction specifically to aspartylglucosaminuria are sparse, the genetic data remain compelling. It is noteworthy that while additional experimental assessments of ASPG enzymatic activity have been performed in other disease contexts, these functional data are not directly aligned with the lysosomal pathology of aspartylglucosaminuria.

In conclusion, the combined evidence from case reports and multi‐patient studies establishes a strong gene–disease association for ASPG with aspartylglucosaminuria. This association supports the use of ASPG variants in diagnostic decision‑making and provides a foundation for future research and commercial diagnostic development.

Key Take‑home: Robust genetic evidence for ASPG in aspartylglucosaminuria underpins its clinical utility as a diagnostic target.

References

• Clinical Genetics • 1997 • Two novel mutations in a Canadian family with aspartylglucosaminuria and early outcome post bone marrow transplantation PMID:9137882
• Proceedings of the National Academy of Sciences of the United States of America • 1991 • Spectrum of mutations in aspartylglucosaminuria PMID:1722323

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