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IEMbase 0017: SLC25A15-related mitochondrial ornithine transporter deficiency

Scope

Field Value
IEMbase ID 17
Nosology 1.1.07.01
Gene SLC25A15
External IDs OMIM:238970
Generated mapping MAPPED by identifier:OMIM:238970
Candidate DisMech targets Hyperornithinemia_Hyperammonemia_Homocitrullinuria_Syndrome.yaml
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents the HHH syndrome triad with characteristic hyperornithinemia, hyperammonemia, and homocitrullinuria. Characteristic clinical features include developmental delay, encephalopathy, coma, vomiting, pyramidal signs, spastic paresis, and stroke-like episodes. Additional features include seizures, ataxia, asterixis, episodic confusion, feeding difficulty/protein aversion, liver dysfunction or acute liver failure, temperature instability, and impaired vision.

The biochemical profile includes high urinary homocitrulline, high plasma ornithine, high ammonia, variably high glutamine, increased transaminases, low incorporation of radiolabeled ornithine in fibroblasts, variably high orotic acid, low/normal urea, and factor VII/X abnormalities. Treatments include arginine or citrulline, protein-defined diet, nitrogen scavengers, hemodialysis, peritoneal dialysis, and liver transplantation.

DisMech phenotype coverage

The generated mapping is correct. DisMech has a detailed HHH entry with intellectual disability, seizures, lethargy, spastic paraplegia, coma, confusion, hypotonia, learning disability, hyperreflexia, decreased liver function, failure to thrive, respiratory alkalosis, hyperammonemia, protein avoidance, ataxia, cerebral cortical atrophy, myoclonic seizures, clonus, hepatomegaly, coordination problems, vibratory-sensation impairment, episodic vomiting, tachypnea, elevated transaminases, oroticaciduria, coagulation abnormality, acute encephalopathy, white-matter abnormalities, pyramidal signs, speech apraxia, feeding difficulties, hyperornithinemia, hepatitis, neurodevelopmental delay, chorioretinal findings, and cognitive impairment. Biochemical coverage includes hyperornithinemia, hyperammonemia, homocitrullinuria, oroticaciduria, and elevated transaminases. Treatments cover protein restriction, citrulline/arginine supplementation, ammonia scavengers, and acute crisis management.

Concordance and completeness

Judgement: high concordance with excellent DisMech phenotype depth. IEMbase is more explicit about certain laboratory diagnostics and dialysis modalities.

IEMbase adds the fibroblast ornithine-transport assay, factor VII/X reductions, and explicit hemodialysis/peritoneal dialysis/liver transplantation rows. DisMech adds a much broader chronic neurologic and ocular phenotype set and better separates pyramidal tract, white-matter, and liver dysfunction.

Curation actions

  • Keep the generated mapping.
  • Consider adding fibroblast ornithine-transport assay and factor VII/X abnormalities as biochemical/coagulation refinements if evidence is available.
  • Consider adding liver transplantation as a treatment if it is intended to be represented for HHH syndrome.