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IEMbase 0426: ISCU-related hereditary myopathy with lactic acidosis

Scope

Field Value
IEMbase ID 426
Nosology 8.2.1.01
Gene ISCU
External IDs OMIM:255125; ORPHA:43115
Generated mapping UNMAPPED; low candidate Charcot-Marie-Tooth_Disease.yaml#HNPP
Candidate DisMech targets No exact local target
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents ISCU-related hereditary myopathy with lactic acidosis (HML), an autosomal recessive disorder of lipoic-acid and iron-sulfur metabolism. Biochemical rows include markedly increased plasma lactate, reduced muscle aconitase, reduced muscle SDH histochemistry, decreased complexes I-III activity, normal-to-increased or increased creatine kinase, and increased urinary myoglobin. Clinical rows include exercise intolerance, muscle weakness, myopathy, myoglobinuria, rhabdomyolysis, and occasional cardiomyopathy. There are no treatment rows.

DisMech phenotype coverage

There is no exact local DisMech target for ISCU-related hereditary myopathy with lactic acidosis. The generated HNPP/Charcot-Marie-Tooth candidate is a false positive: local CMT/HNPP entries concern inherited peripheral neuropathy, especially PMP22 duplication/deletion, Schwann-cell dysfunction, and length-dependent neuropathy or pressure palsies. They do not cover ISCU, iron-sulfur cluster biogenesis, aconitase/SDH deficiency, exercise-induced lactic acidosis, rhabdomyolysis, or myoglobinuria.

Local Friedreich ataxia mentions ISCU2 only as part of the mitochondrial Fe-S cluster assembly machinery affected secondarily by frataxin deficiency; it is not an ISCU-HML disease entry.

Concordance and completeness

Judgement: true local gap; reject the CMT/HNPP candidate.

IEMbase's signal is a metabolic mitochondrial myopathy with iron-sulfur cluster enzyme defects and exercise-triggered lactic acidosis. The candidate is a phenotype-neighbor neuropathy grouping and does not share gene, proximal mechanism, biochemical signature, or clinical course.

Curation actions

  • Keep this record unmapped until an ISCU hereditary myopathy with lactic acidosis target exists.
  • Do not map to Charcot-Marie-Tooth_Disease.yaml or HNPP.
  • If curated, include ISCU, autosomal recessive inheritance, Fe-S cluster biogenesis, reduced aconitase/SDH/complex I-III activity, lactate, exercise intolerance, myopathy, muscle weakness, rhabdomyolysis, myoglobinuria, and cardiomyopathy as an occasional feature.