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IEMbase 0140: ADSL-related Adenylosuccinate lyase deficiency

Scope

Field Value
IEMbase ID 140
Nosology 16.2.03.01
Gene ADSL
External IDs OMIM:103050; OMIM:608222; ORPHA:46
Generated mapping MAPPED, high confidence
Candidate DisMech targets Adenylosuccinate_Lyase_Deficiency.yaml
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents this as ADSL-related adenylosuccinate lyase deficiency, with alternate label adenylosuccinase deficiency and abbreviation ADSLD. Treatability is marked unknown.

Characteristic biochemical rows include increased SAICA riboside in CSF, plasma, and urine, and increased succinyladenosine in CSF, plasma, and urine. The enzyme-testing row records markedly decreased RBC adenylosuccinate lyase activity. Clinical rows include autism, cerebellar hypoplasia, cerebral hypomyelination, epilepsy, hypotonia, and psychomotor delay. No treatment rows are listed.

DisMech phenotype coverage

Adenylosuccinate_Lyase_Deficiency.yaml is the correct local target. It models ADSL deficiency as an ultra-rare autosomal recessive purine-metabolism disorder with reduced adenylosuccinate lyase activity, impaired de novo purine synthesis and purine nucleotide-cycle flux, and accumulation of the dephosphorylated ADSL substrates SAICAr and S-Ado.

The local entry includes severe and mild subtypes plus a fatal neonatal form. Phenotype coverage includes severe global developmental delay, intellectual disability, seizures, generalized hypotonia, absent speech, autistic behavior, microcephaly, craniofacial dysmorphism, cerebral white-matter MRI abnormalities, cerebral atrophy, and cerebellar atrophy. Biochemical coverage includes reduced ADSL activity, increased succinylpurines, and succinyladenosine. Treatments include seizure-directed supportive care and investigational allopurinol therapy.

Concordance and completeness

Judgement: correct mapping with strong local coverage.

IEMbase and DisMech agree on ADSL deficiency, succinylpurine accumulation, reduced enzyme activity, epilepsy, hypotonia, autism/autistic behavior, white matter involvement, and psychomotor/developmental delay. DisMech is richer for subtypes, mechanism, dysmorphism, broader neurologic outcomes, and treatment context. IEMbase adds compartment-specific SAICA riboside and succinyladenosine rows across CSF, plasma, and urine, plus cerebellar hypoplasia wording that should be reviewed against the local cerebellar atrophy representation.

Curation actions

  • Keep Adenylosuccinate_Lyase_Deficiency.yaml as the canonical target.
  • Consider adding explicit SAICA riboside rows by specimen if the biochemical panel is expanded.
  • Review cerebellar hypoplasia versus cerebellar atrophy wording before adding a new structural brain phenotype.