MD Reference Resources
Aspartylglucosaminuria's Clinical Features
Aspartylglucosaminuria (AGU) is a rare genetic, autosomal recessive disease that belongs to a group of metabolism diseases with inborn errors containing the following designations: OMIM #208400, 2021 ICD-10-CM Diagnosis Code E77.1, and ICD-11 Code 5C56.2. Aspartylglucosaminuria is part of a group of ~50 different lysosomal storage disorders. The symptoms of Aspartylglucosaminuria are caused by a malfunction of a lysosomal enzyme necessary to breakdown glycoproteins.
Most of the reported medical information on AGU involves Finnish patients, due to the effect of one major Finnish mutation. Over 30 different mutations in patients of non-Finnish ancestry were reported in 2001, and more are discovered every year. Patients with different mutations can have completely different symptoms, as well as milder or more profound symptoms, compared to patients with the Finnish mutation.
In general, pregnancy and infancy are normal and all babies look healthy. Once born, girls may have umbilical and boys may have inguinal hernias. Babies and toddlers have above average respiratory infections and long periods of diarrhea. Early growth spurts usually occur during the first months of life.
Delayed speech, attention deficit, clumsiness, restlessness, continued respiratory infections, and long periods of diarrhea are present in most of the preschoolers.
Intellectual disabilities progressively worsen in adolescence. Most people with this disorder lose much of the speech they have learned, and affected adults often only have a few words in their vocabulary. Adults with AGU may develop seizures or problems with movement.
Typical Development of Finnish AGU patient (based on work of Dr. Maria Arvio)
All patients with AGU excrete large amounts of aspartylglucosamine in their urine. Biochemical screening tests should be done by urine chromatography in certified labs only.
Genetic testing can prove the diagnosis at the following Labs. The list includes US and global laboratories.
Greenwood Genetic Center in the US developed vast expertise with AGU and other lysosomal storage disorder testing.
Blood enzyme assay is also done at Manchester Saint Mary's Hospital in the UK.
What Causes Aspartylglucosaminuria?
Aspartylglucosaminuria (AGU) is a rare genetic, autosomal recessive disease that belongs to a group of metabolism diseases with inborn errors containing the following designations: OMIM #208400, ICD-10-CM Diagnosis Code E77.1, and ICD-11 Code 5C56.21. Aspartylglucosaminuria is part of a group of ~50 different lysosomal storage disorders.
Aspartylglucosaminuria is a genetic disorder that is caused by the malfunction of a gene called aspartylglucosaminidase (NIH Genetics Reference). Exon and intron sequences can be found in GenBank: U21273–U21281. The gene encodes a 346-amino acid single-chain polypeptide. Self-cleavage of the nascent single-chain precursor occurs between residues D205 and T206 to form an active α/β-glycosylasparaginase enzyme (EC 22.214.171.124), or more specifically N(4)-(beta-N-acetylglucosaminyl)-L-asparaginase.
Aspartylglucosaminidase (AGA) Enzyme Role
Aspartylglucosaminidase is a proteolytic (digestive) enzyme that degrades (breaks down) glycoproteins via hydrolytic deglycosylation. It is a member of a family called the Ntn (N-terminal nucleophilic) hydrolases.
These enzymes are characterized by coding as a large pre-protein and are post-translationally cleaved by autoproteolysis to create α- and β-subunits and a new N-terminal amino acid.
The heterotetrameric AGA enzyme has two active sites, consisting of an essential conserved β-chain N-terminal threonine within an active site of deep conical profile. The enzyme is novel in that it requires both the α-amino and the α-carboxyl group of the substituted amino acid residue to be free. Additionally, the same Thr residue is involved both in genesis of the active enzyme, and in catalytic function of the active site.