Multiple mitochondrial dysfunctions syndrome type 4
Synonyms: MMDS4
- Type
- Disease
- Group
- Disorder
- Inheritance
- Autosomal recessive
- Age of onset
- Infancy
- Status
- active
A rare, severe, genetic, neurometabolic disease characterized by infantile-onset of progressive neurodevelopmental regression, optic atrophy with nystagmus and diffuse white matter disease. Affected individuals usually have central hypotonia that progresses to limb spasticity and hyperreflexia, eventually resulting in a vegetative state. Recurrent chest infections are frequently associated and seizures (usually generalized tonic-clonic) may occasionally be observed. Brain magnetic resonance imaging shows diffuse bilateral symmetric abnormalities in the cerebral periventricular white matter, with variable lesions in other areas but sparing the basal ganglia.
Names in Orphadata languages
12 of 12 languages| Lang | Name | Synonyms |
|---|---|---|
| en | Multiple mitochondrial dysfunctions syndrome type 4 | MMDS4 |
| fr | Syndrome de dysfonctionnements mitochondriaux multiples type 4 | |
| de | Syndrom der multiplen mitochondrialen Dysfunktionen Typ 4 | |
| es | Síndrome de disfunción mitocondrial múltiple tipo 4 | |
| it | Sindrome da disfunzioni mitocondriali multiple tipo 4 | |
| nl | Multipele mitochondriale disfuncties-syndroom type 4 | |
| pt | Síndrome de disfunção mitocondrial múltipla, forma fatal tipo 4 | |
| pl | Śmiertelny zespół mnogich dysfunkcji mitochondrialnych typu 4 | = en |
| cs | Syndrom fatálních mnohočetných mitochondriálních dysfunkcí, typ 4 | = en |
| uk | Синдром множинних мітохондріальних дисфункцій, тип 4 | = en |
| zh | 多发性线粒体功能障碍综合征4型 | = en |
| tr | Çoklu mitokondriyal disfonksiyon sendromu tip 4 | = en |
Definition in:
Cross-references
qualifier = Orphanet mapping relation| Source | Code | Qualifier | ICD relation | Validation |
|---|---|---|---|---|
| OMIM | 616370 | E | validated | |
| ICD-10 | E88.8 | NTBT | attributed | validated |
| ICD-11 | 5C53.2Y | NTBT | attributed | validated |
| MONDO | 0014611 | E | validated | |
| UMLS | C4225348 | 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 (5):
- ORPHA:183500Genetic neurodegenerative disease
rare genetic diseases - ORPHA:68356Leukodystrophy
rare genetic diseases; rare neurological diseases - ORPHA:289573Multiple mitochondrial dysfunctions syndrome
rare inborn errors of metabolism; rare genetic diseases; rare neurological diseases - ORPHA:182070Rare neurodegenerative disease
rare neurological diseases - ORPHA:441434Syndromic hereditary optic neuropathy
rare genetic diseases; rare ophthalmic disorders
No children.
Genes
1 direct| Gene | Association | Status | HGNC | Ensembl | OMIM | Locus | Name | Source of validation |
|---|---|---|---|---|---|---|---|---|
| ISCA2 | Disease-causing germline mutation(s) in | Assessed | HGNC:19857 | ENSG00000165898 | 615317 | 14q24.3 | iron-sulfur cluster assembly 2 | 25539947[PMID] |
Prevalence and incidence
2 records| Type | Class | Value | Area | Qualification | Validation | Source |
|---|---|---|---|---|---|---|
| Cases/families | 8 cases | Worldwide | Case(s) | Validated | 25539947[PMID] | |
| Point prevalence | <1 / 1 000 000 | — | Worldwide | Class only | Validated | ORPHANET_25539947[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
22 annotations · validated 2026-01-30| HPO | Term (as annotated by Orphanet) | Diagnostic |
|---|---|---|
| Very frequent (99-80%) | ||
| HP:0034353 | Appendicular spasticity | |
| HP:0002376 | Developmental regression | |
| HP:0001263 | Global developmental delay | |
| HP:0000648 | Optic atrophy | |
| HP:0000572 | Visual loss | |
| Frequent (79-30%) | ||
| HP:0001252 | Hypotonia | |
| HP:0002415 | Leukodystrophy | |
| HP:0000639 | Nystagmus | |
| HP:0031358 | Vegetative state | |
| Occasional (29-5%) | ||
| HP:0008314 | Decreased activity of mitochondrial complex II | |
| HP:0008347 | Decreased activity of mitochondrial complex IV | |
| HP:0001332 | Dystonia | |
| HP:0034893 | Elevated brain glycine level by MRS | |
| HP:0012707 | Elevated brain lactate level by MRS | |
| HP:0002154 | Hyperglycinemia | |
| HP:0001347 | Hyperreflexia | |
| HP:0500200 | Increased CSF glutamate concentration | |
| HP:0500230 | Increased CSF glycine concentration | |
| HP:0002490 | Increased CSF lactate | |
| HP:0002151 | Increased circulating lactate concentration | |
| HP:0002205 | Recurrent respiratory infections | |
| HP:0001250 | Seizure | |
Run the differential on the 5 obligate / very frequent terms
Annotation source: 32424628[PMID]_31106229[PMID]_31279336[PMID]_29470032[PMID]
Sources for this card
- Orphanet page: orpha.net/en/disease/detail/457406
- This record as JSON: /data/d/457406.json