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IEMbase 0578: AP1S1-related MEDNIK syndrome

Scope

Field Value
IEMbase ID 578
Nosology 22.1.04.01
Gene AP1S1
External IDs OMIM:609313; ORPHA:171851
Generated mapping MAPPED; MEDNIK_syndrome.yaml
Candidate DisMech targets MEDNIK_syndrome.yaml
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents AP1S1-related MEDNIK syndrome, with alternate label mental retardation, enteropathy, deafness, peripheral neuropathy, ichthyosis, and keratoderma. The record is autosomal recessive, classified under disorders of copper metabolism, flagged as treatable, and lists zinc acetate.

Biochemical rows include increased plasma ASAT/ALAT, increased plasma bile acids by enzyme assay, decreased serum ceruloplasmin, decreased serum copper, and increased plasma very-long-chain fatty acids. Clinical rows add cerebral atrophy on MRI, hyperkeratosis, and intestinal pseudo-obstruction.

DisMech phenotype coverage

MEDNIK_syndrome.yaml is the correct local target. It models autosomal recessive AP1S1 disease with adaptor-protein trafficking dysfunction, mislocalization of copper pumps, copper-handling defects, intestinal barrier dysfunction, and the core MEDNIK phenotype of enteropathy, deafness, peripheral neuropathy, ichthyosis, keratoderma, neurodevelopmental involvement, and liver copper overload. Zinc acetate therapy is also represented.

Concordance and completeness

Judgement: correct exact mapping.

IEMbase and DisMech agree on the AP1S1 identity, recessive inheritance, MEDNIK syndrome label, copper-metabolism framing, enteropathy, deafness, peripheral neuropathy, ichthyosis/keratoderma, and zinc treatment signal. DisMech is stronger for the trafficking and copper-pump mechanism.

IEMbase adds useful import prompts for low serum copper and ceruloplasmin, ASAT/ALAT and bile-acid abnormalities, very-long-chain fatty acids, cerebral atrophy, hyperkeratosis wording, and intestinal pseudo-obstruction.

Curation actions

  • Keep MEDNIK_syndrome.yaml as the exact DisMech target.
  • Review the IEMbase serum copper/ceruloplasmin, ASAT/ALAT, bile-acid, and very-long-chain fatty-acid rows against the local hepatic/copper mechanism.
  • Consider adding cerebral atrophy, hyperkeratosis, and intestinal pseudo-obstruction only after source-level confirmation.