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IEMbase 0090: MMACHC-related methylmalonic aciduria and homocystinuria, cblC type

Scope

Field Value
IEMbase ID 90
Nosology 21.9.09.01
Gene MMACHC
External IDs OMIM:277400
Generated mapping MAPPED to Inborn_Disorder_of_Cobalamin_Metabolism_and_Transport.yaml#cblC
Candidate DisMech targets MMACHC-related_Methylmalonic_Aciduria_and_Homocystinuria_cblC_Type.yaml; Inborn_Disorder_of_Cobalamin_Metabolism_and_Transport.yaml#cblC
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents this as autosomal recessive MMACHC-related cblC disease, with alternate labels B12-responsive MMA and homocystinuria and cblC. Treatability is marked yes.

The characteristic clinical rows include megaloblastic anemia, failure to thrive, life-threatening illness, neurologic dysfunction, and impaired vision.

The biochemical panel includes elevated urinary and plasma methylmalonic acid, urinary methylcitric acid, urinary 3-hydroxypropionic acid, C3 propionylcarnitine in blood or plasma, urinary and plasma homocysteine, low-to-normal methionine, and reduced S-adenosylmethionine in CSF or plasma.

Treatment rows include betaine, hydroxycobalamin, and carnitine.

DisMech phenotype coverage

The generated mapping to the cobalamin umbrella's cblC subtype is biologically correct, but the best canonical DisMech target is the standalone MMACHC-related_Methylmalonic_Aciduria_and_Homocystinuria_cblC_Type.yaml entry.

The standalone cblC entry has direct MMACHC pathophysiology, methylcobalamin and adenosylcobalamin branch failure, homocysteine and methylmalonic acid accumulation, early- and late-onset subtypes, neurologic and ocular injury, renal and vascular complications, and hydroxocobalamin plus betaine treatment. The cobalamin umbrella also covers cblC as a subtype and is useful secondary context, but it is less specific than the standalone disease file.

Concordance and completeness

Judgement: correct disease-level coverage with a canonical-target ambiguity.

IEMbase adds some compact panel details, especially S-adenosylmethionine and C3/3-hydroxypropionate/methylcitric-acid rows. DisMech is richer for mechanism, genotype, vascular and renal complications, and treatment rationale.

Curation actions

  • Prefer MMACHC-related_Methylmalonic_Aciduria_and_Homocystinuria_cblC_Type.yaml as the canonical target for this record.
  • Keep Inborn_Disorder_of_Cobalamin_Metabolism_and_Transport.yaml#cblC as umbrella context rather than the primary mapping.
  • Consider aligning duplicate cblC coverage so future crosswalks consistently prefer the standalone file when a distinct MONDO disease entry exists.