IEMbase 0282: DNM1L-related Dynamin-like protein 1 deficiency
Scope
| Field | Value |
|---|---|
| IEMbase ID | 282 |
| Nosology | 19.2.01.01 |
| Gene | DNM1L |
| External IDs | OMIM:614388; ORPHA:98673 |
| Generated mapping | UNMAPPED; weak candidate Pyruvate_Dehydrogenase_Deficiency.yaml |
| Candidate DisMech targets | None valid |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents DNM1L-related defective mitochondrial and peroxisomal fission encephalopathy. The alternate label in the cache is "Encephalopahty, lethal, due to defective mitochondrial peroxisomal fission" with the spelling preserved from IEMbase. Inheritance is listed as autosomal dominant and autosomal recessive. Treatability is unknown.
The phenotype signal is a severe early neurologic disorder: neonatal abnormal gyral pattern, delayed myelination, hypotonia, microcephaly, muscle weakness, areflexia, optic atrophy, failure to thrive, later cerebral atrophy, oculomotor apraxia, psychomotor delay, pyramidal signs, neurologic regression, and seizures. The biochemical rows list increased plasma lactate and increased plasma very-long-chain fatty acids.
DisMech phenotype coverage
There is no local DisMech disease entry for DNM1L-related mitochondrial and peroxisomal fission defect. Repository search finds DNM1L mentioned only as context in unrelated entries such as obesity, while other dynamin-family or mitochondrial-dynamics entries involve different genes and disease entities.
The generated weak candidate, Pyruvate_Dehydrogenase_Deficiency.yaml, is not
a valid target. PDH deficiency can share lactic acidosis and neurologic
features, but it does not model the DNM1L/DRP1 fission mechanism, the combined
mitochondrial-peroxisomal dynamics defect, or the associated VLCFA abnormality.
Concordance and completeness
Judgement: true local gap; do not map to the weak PDH candidate.
IEMbase provides a compact but coherent DNM1L phenotype profile centered on early encephalopathy, abnormal brain development/myelination, optic atrophy, regression, seizures, hypotonia, lactate elevation, and VLCFA elevation. DisMech currently lacks a corresponding disease-level entry, and the existing mitochondrial/peroxisomal entries do not cover this fission-dynamics disorder.
This is a useful future curation target because it crosses organelle biogenesis/dynamics and peroxisomal metabolic readouts. Any future entry should distinguish DNM1L from MFF and other mitochondrial fission genes, and should separate primary fission biology from secondary lactic acidosis or peroxisomal fatty-acid abnormalities.
Curation actions
- Leave this record unmapped for now.
- Reject
Pyruvate_Dehydrogenase_Deficiency.yamlas a false-positive metabolic encephalopathy candidate. - Consider a future standalone DNM1L entry or a mitochondrial/peroxisomal dynamics grouping that can also accommodate later MFF-related records.