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IEMbase 0258: AGA-related Aspartylglucosaminidase deficiency

Scope

Field Value
IEMbase ID 258
Nosology 20.3.07.01
Gene AGA
External IDs OMIM:208400; ORPHA:93
Generated mapping MAPPED; Aspartylglucosaminuria.yaml
Candidate DisMech targets Aspartylglucosaminuria.yaml
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents this as AGA-related aspartylglucosaminidase deficiency, with alternate labels aspartylglucosaminuria and AGU. The record is autosomal recessive and treatability is marked yes.

The treatment section lists hematopoietic stem cell transplant as a stem-cell strategy with level 4-5 evidence and PMID 15316370. Biochemical rows include decreased aspartylglucosaminidase activity in fibroblasts, lymphocytes, and white blood cells, plus increased urinary aspartylglucosamine. Clinical rows include angiokeratoma, clubfoot, axial muscular hypotonia, and vacuolated lymphocytes.

DisMech phenotype coverage

Aspartylglucosaminuria.yaml is the correct local target. The local entry covers biallelic AGA pathogenic variants, deficient lysosomal aspartylglucosaminidase/glycosylasparaginase activity, glycoasparagine and aspartylglucosamine accumulation, urinary aspartylglucosamine, progressive neurodevelopmental and behavioral disease, seizures, speech impairment, systemic connective-tissue and skeletal findings, recurrent infections, hepatosplenic involvement, enzyme testing, molecular testing, supportive care, hematopoietic stem cell transplantation with lack-of-benefit caveats, preclinical enzyme replacement, and preclinical AAV9/AGA therapy.

Concordance and completeness

Judgement: correct mapping with high biochemical concordance and a treatment interpretation caveat.

IEMbase and DisMech agree on AGA/AGU identity, autosomal recessive inheritance, reduced aspartylglucosaminidase activity, and urinary aspartylglucosamine elevation. IEMbase adds concise rows for angiokeratoma, clubfoot, axial hypotonia, and vacuolated lymphocytes. DisMech is much broader clinically and mechanistically. The treatment rows need nuance: IEMbase lists transplant as a treatment, whereas DisMech explicitly records that limited transplant attempts have not shown clear benefit.

Curation actions

  • Keep this record mapped to Aspartylglucosaminuria.yaml.
  • Do not import the transplant row as unqualified effective therapy without the local lack-of-benefit caveat.
  • Use IEMbase's angiokeratoma, clubfoot, axial hypotonia, and vacuolated lymphocyte rows as future phenotype review prompts.