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IEMbase 0091: LMBRD1-related methylmalonic aciduria and homocystinuria, cblF type

Scope

Field Value
IEMbase ID 91
Nosology 21.9.07.01
Gene LMBRD1
External IDs OMIM:277380
Generated mapping MAPPED to Inborn_Disorder_of_Cobalamin_Metabolism_and_Transport.yaml#cblF
Candidate DisMech targets Inborn_Disorder_of_Cobalamin_Metabolism_and_Transport.yaml#cblF
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents this as autosomal recessive LMBRD1-related cblF disease, with alternate labels lysosomal membrane cobalamin transporter deficiency and cblF. 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 matches combined methylmalonic aciduria and homocystinuria: 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 hydroxocobalamin and betaine.

DisMech phenotype coverage

The generated mapping is correct. The best local target is Inborn_Disorder_of_Cobalamin_Metabolism_and_Transport.yaml#cblF.

DisMech's cblF subtype describes LMBRD1 deficiency as impaired lysosomal export of cobalamin producing combined methylmalonic acidemia and homocystinuria. The umbrella pathophysiology explicitly includes LMBRD1 in defective cobalamin absorption, transport, and cellular uptake, leading to impaired intracellular cobalamin cofactor synthesis, remethylation failure, and methylmalonyl-CoA mutase dysfunction.

Concordance and completeness

Judgement: high concordance at the umbrella subtype level.

The main local gaps are cblF-specific presentation detail and lab-compartment granularity. IEMbase is more explicit about the cblF clinical row set and S-adenosylmethionine markers, while DisMech carries stronger generalized cobalamin-transport mechanism and treatment rationale.

Curation actions

  • Keep the generated mapping to Inborn_Disorder_of_Cobalamin_Metabolism_and_Transport.yaml#cblF.
  • Consider adding cblF-specific clinical and biochemical notes if the umbrella entry is expanded.
  • Preserve spelling-normalization handling: the IEMbase name currently contains "LMBRD1-relasted" while the intended label is LMBRD1-related.