Multiple mitochondrial dysfunctions syndrome type 2
Synonyms: BOLA3 deficiency · MMDS2
- Type
- Disease
- Group
- Disorder
- Inheritance
- Autosomal recessive
- Age of onset
- Neonatal
- Status
- active
A rare mitochondrial disease characterized by infantile onset of severe regression after a period of normal development, epileptic encephalopathy, hypotonia, movement disorder, cardiomyopathy, hyperglycinemia, and lactic acidosis. Optic atrophy may also be present. Brain imaging findings are highly variable and include white matter abnormalities. The disease is typically fatal in infancy.
Names in Orphadata languages
12 of 12 languages| Lang | Name | Synonyms |
|---|---|---|
| en | Multiple mitochondrial dysfunctions syndrome type 2 | BOLA3 deficiency · MMDS2 |
| fr | Syndrome de dysfonctionnements mitochondriaux multiples type 2 | Déficit en BOLA3 |
| de | Syndrom der multiplen mitochondrialen Dysfunktionen Typ 2 | BOLA3-Mangel |
| es | Síndrome de disfunción mitocondrial múltiple tipo 2 | Deficiencia de BOLA3 |
| it | Sindrome da disfunzione mitocondriale multipla tipo 2 | Deficit di BOLA3 |
| nl | Multipele mitochondriale disfuncties-syndroom type 2 | BOLA3-deficiëntie |
| pt | Síndrome de disfunção mitocondrial múltipla, forma fatal tipo 2 | |
| pl | Zespół śmiertelnej mnogiej dysfunkcji mitochondriów typu 2 | Niedobór BOLA3 |
| cs | Syndrom fatálních mnohočetných mitochondriálních dysfunkcí, typ 2 | Deficit BOLA3 |
| uk | Синдром множинних мітохондріальних дисфункцій, тип 2 | Дефіцит BOLA3 · MMDS2 |
| zh | 多发性线粒体功能障碍综合征2型 | BOLA3缺陷 |
| tr | Çoklu mitokondriyal disfonksiyon sendromu tip 2 | MMDS2 · BOLA3 eksikliği |
Definition in:
Cross-references
qualifier = Orphanet mapping relation| Source | Code | Qualifier | ICD relation | Validation |
|---|---|---|---|---|
| OMIM | 614299 | E | validated | |
| ICD-10 | E88.8 | NTBT | attributed | validated |
| ICD-11 | 5C53.21 | NTBT | attributed | validated |
| MONDO | 0013675 | E | validated | |
| UMLS | C3280378 | E | validated |
E exact · NTBT this ORPHAcode is narrower than the target · BTNT broader than the target · ND not decided.
Classification
Preferential parent (Orphanet linearisation):
Parents in the classifications (1):
- ORPHA:289573Multiple mitochondrial dysfunctions syndrome
rare inborn errors of metabolism; rare genetic diseases; rare neurological diseases
No children.
Genes
1 direct| Gene | Association | Status | HGNC | Ensembl | OMIM | Locus | Name | Source of validation |
|---|---|---|---|---|---|---|---|---|
| BOLA3 | Disease-causing germline mutation(s) in | Assessed | HGNC:24415 | ENSG00000163170 | 613183 | 2p13.1 | bolA family member 3 | 24334290[PMID]_24777537[PMID] |
Prevalence and incidence
2 records| Type | Class | Value | Area | Qualification | Validation | Source |
|---|---|---|---|---|---|---|
| Cases/families | 6 cases | Worldwide | Case(s) | Validated | 24777537[PMID]_21944046[PMID]_24334290[PMID]_22562699[PMID] | |
| Point prevalence | <1 / 1 000 000 | — | Worldwide | Class only | Validated | ORPHANET_24777537[PMID]_21944046[PMID]_24334290[PMID]_22562699[PMID] |
Value is Orphadata's ValMoy: the mean estimate per 100 000 for prevalence and incidence, the number of cases or families for case reports.
HPO phenotypes
28 annotations · validated 2026-01-21| HPO | Term (as annotated by Orphanet) | Diagnostic |
|---|---|---|
| Frequent (79-30%) | ||
| HP:0011400 | Abnormal CNS myelination | |
| HP:0011923 | Decreased activity of mitochondrial complex I | |
| HP:0008314 | Decreased activity of mitochondrial complex II | |
| HP:0002928 | Decreased activity of the pyruvate dehydrogenase complex | |
| HP:0002376 | Developmental regression | |
| HP:0200134 | Epileptic encephalopathy | |
| HP:0008872 | Feeding difficulties in infancy | |
| HP:0001263 | Global developmental delay | |
| HP:0001639 | Hypertrophic cardiomyopathy | |
| HP:0001252 | Hypotonia | |
| HP:0002151 | Increased circulating lactate concentration | |
| HP:0002878 | Respiratory failure | |
| HP:0001257 | Spasticity | |
| Occasional (29-5%) | ||
| HP:0001272 | Cerebellar atrophy | |
| HP:0002059 | Cerebral atrophy | |
| HP:0001644 | Dilated cardiomyopathy | |
| HP:0034659 | Elevated urine tiglylglycine level | |
| HP:0002240 | Hepatomegaly | |
| HP:0002154 | Hyperglycinemia | |
| HP:0003108 | Hyperglycinuria | |
| HP:0500230 | Increased CSF glycine concentration | |
| HP:0002490 | Increased CSF lactate | |
| HP:0003542 | Increased circulating pyruvate concentration | |
| HP:0001254 | Lethargy | |
| HP:0001942 | Metabolic acidosis | |
| HP:0001336 | Myoclonus | |
| HP:0000639 | Nystagmus | |
| HP:0001250 | Seizure | |
Annotation source: 34440194[PMID]_30302924[PMID]
Sources for this card
- Orphanet page: orpha.net/en/disease/detail/401874
- This record as JSON: /data/d/401874.json