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IEMbase 0778: OAS1-related 2-prime,5-prime-oligoadenylate synthetase 1 deficiency

Scope

Field Value
IEMbase ID 778
Nosology 16.3.1.01
Nosology code IEM0035
Gene OAS1
External IDs OMIM:222100
Generated mapping UNMAPPED; weak candidate Holocarboxylase_Synthetase_Deficiency.yaml
Candidate DisMech targets None accepted; broad phenotype overlap only with hereditary PAP entries
Review date 2026-07-08

IEMbase phenotype signal

IEMbase labels this autosomal dominant record as OAS1-related 2-prime,5-prime-oligoadenylate synthetase 1 deficiency, with alternate name infantile-onset pulmonary alveolar proteinosis with hypogammaglobulinemia (PAPHG). The source signal combines pulmonary alveolar proteinosis, recurrent respiratory infections, respiratory failure, increased susceptibility to viral infection, failure to thrive, splenomegaly, early death, small non-foamy alveolar macrophages on bronchoalveolar lavage, low IgG/immunoglobulins, and a low leukocyte laboratory row. The source clinical table labels a leukocytosis row, which conflicts with the low leukocyte laboratory direction and should be reviewed.

DisMech phenotype coverage

No local DisMech disease represents OAS1/PAPHG. The generated candidate, Holocarboxylase_Synthetase_Deficiency.yaml, is a different HLCS biotin-dependent multiple carboxylase deficiency and should be rejected despite weak lexical similarity.

Hereditary_Pulmonary_Alveolar_Proteinosis.yaml overlaps phenotypically for pulmonary alveolar proteinosis, failure to thrive, respiratory failure, and infection risk, but it is explicitly a CSF2RA/CSF2RB GM-CSF receptor disorder with autosomal recessive inheritance and foamy macrophage/surfactant-clearance biology. It does not cover OAS1, autosomal dominant inheritance, hypogammaglobulinemia, viral susceptibility, leukopenia, or the small non-foamy macrophage signal.

Concordance and completeness

Judgement: true local gap; reject the holocarboxylase candidate and do not collapse into hereditary PAP.

The pulmonary phenotype overlap is not sufficient for disease coverage because the gene, inheritance, immune phenotype, and macrophage biology differ. This is best treated as a missing OAS1/PAPHG entity, with hereditary PAP as a future differential/neighbor rather than a mapping target.

Curation actions

  • Treat IEMbase 0778 as an unmapped OAS1/PAPHG gap.
  • Reject Holocarboxylase_Synthetase_Deficiency.yaml as a false candidate.
  • Do not use Hereditary_Pulmonary_Alveolar_Proteinosis.yaml as exact coverage; retain it only as broad pulmonary phenotype context.
  • If curated later, preserve hypogammaglobulinemia, viral susceptibility, leukocyte-count ambiguity, small non-foamy alveolar macrophages, respiratory failure, splenomegaly, and early death.