ORPHA:512
Metachromatic leukodystrophy
Synonyms: Arylsulfatase A deficiency · MLD
- Type
- Disease
- Group
- Disorder
- Inheritance
- Autosomal recessive
- Age of onset
- Adolescent, Adult, Childhood, Infancy
- Status
- active
A rare lysosomal disease characterized by accumulation of sulfatides in the central and peripheral nervous system due to deficiency of the enzyme arylsulfatase A, leading to demyelination. Three clinical subtypes can be distinguished based on the age of onset: late infantile, juvenile, and adult. Lead symptoms are deterioration in motor or cognitive function or behavioral problems, depending on the subtype, all eventually culminating in a decerebrated state and death after a highly variable disease course and duration. Mode of inheritance is autosomal recessive.
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Names in Orphadata languages
12 of 12 languages| Lang | Name | Synonyms |
|---|---|---|
| en | Metachromatic leukodystrophy | Arylsulfatase A deficiency · MLD |
| fr | Leucodystrophie métachromatique | Déficit en arylsulfatase A · MLD |
| de | Leukodystrophie, metachromatische | Arylsulfatase A-Mangel · MLD |
| es | Leucodistrofia metacromática | Deficiencia de arilsulfatasa A · MLD |
| it | Leucodistrofia metacromatica | Deficit di arilsulfatasi A · MLD |
| nl | Metachromatische leukodystrofie | Arylsulfatase A-deficiëntie · MLD |
| pt | Leucodistrofia metacromática | Deficiência de arilsulfatase A |
| pl | Leukodystrofia metachromatyczna | MLD · Niedobór arylosulfatazy A |
| cs | Metachromatická leukodystrofie | Deficit arylsulfatázy A · MLD |
| uk | Метахроматична лейкодистрофія | Дефіцит арилсульфатази А · MLD |
| zh | 异染性脑白质营养不良 | 芳香基硫酸酯酶A缺乏症 |
| tr | Metakromatik lökodistrofi | MLD · Arilsülfataz A eksikliği |
Definition in:
2
Cross-references
qualifier = Orphanet mapping relation| Source | Code | Qualifier | ICD relation | Validation |
|---|---|---|---|---|
| OMIM | 156310 | BTNT | validated | |
| OMIM | 249900 | BTNT | validated | |
| OMIM | 250100 | E | validated | |
| ICD-10 | E75.2 | NTBT | inclusion | validated |
| ICD-11 | 5C56.02 | E | specific | validated |
| MONDO | 0018868 | E | validated | |
| MeSH | D007966 | E | validated | |
| UMLS | C0023522 | E | validated | |
| GARD | 3230 | E | validated | |
| MedDRA | 10067609 | E | validated |
E exact · NTBT this ORPHAcode is narrower than the target · BTNT broader than the target · ND not decided.
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Classification
Preferential parent (Orphanet linearisation):
Parents in the classifications (7):
- ORPHA:68356Leukodystrophy
rare genetic diseases; rare neurological diseases - ORPHA:98543Metabolic disease with dementia
rare genetic diseases; rare neurological diseases - ORPHA:68385Neurometabolic disease
rare genetic diseases; rare neurological diseases - ORPHA:207018Rare hereditary metabolic disease with peripheral neuropathy
rare genetic diseases; rare neurological diseases - ORPHA:79225Sphingolipidosis
rare inborn errors of metabolism; rare genetic diseases; rare transplant-related disorders - ORPHA:371442Sphingolipidosis with epilepsy
rare genetic diseases; rare neurological diseases - ORPHA:441434Syndromic hereditary optic neuropathy
rare genetic diseases; rare ophthalmic disorders
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Genes
0 direct · 6 via subtypesOrphanet records no gene directly on this code.
Recorded by Orphanet on subtypes of this disorder:
| Gene | Subtype | Association | Status | HGNC | Ensembl | OMIM | Locus | Name | Source of validation |
|---|---|---|---|---|---|---|---|---|---|
| ARSA | ORPHA:309256Metachromatic leukodystrophy, late infantile form | Disease-causing germline mutation(s) (loss of function) in | Assessed | HGNC:713 | ENSG00000100299 | 607574 | 22q13.33 | arylsulfatase A | 20301309[PMID] |
| ARSA | ORPHA:309263Metachromatic leukodystrophy, juvenile form | Disease-causing germline mutation(s) (loss of function) in | Assessed | HGNC:713 | ENSG00000100299 | 607574 | 22q13.33 | arylsulfatase A | 20301309[PMID] |
| ARSA | ORPHA:309271Metachromatic leukodystrophy, adult form | Disease-causing germline mutation(s) (loss of function) in | Assessed | HGNC:713 | ENSG00000100299 | 607574 | 22q13.33 | arylsulfatase A | 20301309[PMID] |
| PSAP | ORPHA:309256Metachromatic leukodystrophy, late infantile form | Disease-causing germline mutation(s) in | Assessed | HGNC:9498 | ENSG00000197746 | 176801 | 10q22.1 | prosaposin | 24478108[PMID] |
| PSAP | ORPHA:309263Metachromatic leukodystrophy, juvenile form | Disease-causing germline mutation(s) in | Assessed | HGNC:9498 | ENSG00000197746 | 176801 | 10q22.1 | prosaposin | 24478108[PMID] |
| PSAP | ORPHA:309271Metachromatic leukodystrophy, adult form | Disease-causing germline mutation(s) in | Assessed | HGNC:9498 | ENSG00000197746 | 176801 | 10q22.1 | prosaposin | 24478108[PMID] |
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Prevalence and incidence
12 records| Type | Class | Value | Area | Qualification | Validation | Source |
|---|---|---|---|---|---|---|
| Prevalence at birth | 1-9 / 100 000 | 1.47 / 100 000 | Europe | Value and class | Validated | 21496291[PMID]_[EXPERT]_European Medicines Agency 2010[OTHER] |
| Point prevalence | 1-9 / 1 000 000 | 0.1 / 100 000 | Europe | Value and class | Validated | 21496291[PMID]_[EXPERT]_European Medicines Agency 2010[OTHER] |
| Prevalence at birth | 1-9 / 100 000 | 1.42 / 100 000 | Netherlands | Value and class | Validated | 10480370[PMID] |
| Prevalence at birth | 1-9 / 100 000 | 1.85 / 100 000 | Portugal | Value and class | Validated | 14685153[PMID] |
| Prevalence at birth | 1-9 / 1 000 000 | 0.6 / 100 000 | Germany | Value and class | Validated | 9286459[PMID] |
| Prevalence at birth | 1-9 / 100 000 | 1.43 / 100 000 | Turkey | Value and class | Validated | 20490927[PMID] |
| Prevalence at birth | 1-9 / 100 000 | 1.09 / 100 000 | Australia | Value and class | Validated | 9918480[PMID] |
| Prevalence at birth | 1-9 / 1 000 000 | 0.69 / 100 000 | Czech Republic | Value and class | Validated | 20490927[PMID] |
| Prevalence at birth | 1-9 / 1 000 000 | 0.38 / 100 000 | Poland | Value and class | Validated | 21695197[PMID] |
| Prevalence at birth | 1-9 / 100 000 | 1.73 / 100 000 | Sweden | Value and class | Validated | 25274184[PMID] |
| Prevalence at birth | 1-9 / 100 000 | 2.5 / 100 000 | United States | Value and class | Validated | 19380076[PMID] |
| Prevalence at birth | 1-9 / 100 000 | — | Worldwide | Class only | Validated | ORPHANET_21695197[PMID]_20490927[PMID]_19380076[PMID]_9918480[PMID]_9286459[PMID]_14685153[PMID]_10480370[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.
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HPO phenotypes
45 annotations · validated 2020-03-09| HPO | Term (as annotated by Orphanet) | Diagnostic |
|---|---|---|
| Very frequent (99-80%) | ||
| HP:0012379 | Abnormal enzyme/coenzyme activity | |
| HP:0006970 | Periventricular leukomalacia | |
| Frequent (79-30%) | ||
| HP:0000649 | Abnormality of visual evoked potentials | |
| HP:0001251 | Ataxia | |
| HP:0000762 | Decreased nerve conduction velocity | |
| HP:0002376 | Developmental regression | |
| HP:0008947 | Floppy infant | |
| HP:0002359 | Frequent falls | |
| HP:0001288 | Gait disturbance | |
| HP:0000365 | Hearing impairment | |
| HP:0030890 | Hyperintensity of cerebral white matter on MRI | |
| HP:0001265 | Hyporeflexia | |
| HP:0002922 | Increased CSF protein concentration | |
| HP:0003394 | Muscle spasm | |
| HP:0001324 | Muscle weakness | |
| HP:0009830 | Peripheral neuropathy | |
| HP:0002191 | Progressive spasticity | |
| HP:0001250 | Seizure | |
| HP:0000505 | Visual impairment | |
| Occasional (29-5%) | ||
| HP:0030858 | Addictive behavior | |
| HP:0000708 | Atypical behavior | |
| HP:0002607 | Bowel incontinence | |
| HP:0000726 | Dementia | |
| HP:0001260 | Dysarthria | |
| HP:0001332 | Dystonia | |
| HP:0000712 | Emotional lability | |
| HP:0011968 | Feeding difficulties | |
| HP:0011471 | Gastrostomy tube feeding in infancy | |
| HP:0031064 | Impaired continence | |
| HP:0002311 | Incoordination | |
| HP:0009763 | Limb pain | |
| HP:0012531 | Pain | |
| HP:0000751 | Personality changes | |
| HP:0000709 | Psychosis | |
| HP:0100753 | Schizophrenia | |
| HP:0030051 | Tip-toe gait | |
| HP:0001337 | Tremor | |
| HP:0000020 | Urinary incontinence | |
| Very rare (<4-1%) | ||
| HP:0012437 | Abnormal gallbladder morphology | |
| HP:0002577 | Abnormal stomach morphology | |
| HP:0002246 | Abnormality of the duodenum | |
| HP:0025013 | Decerebrate rigidity | |
| HP:0100762 | Hemobilia | |
| HP:0002576 | Intussusception | |
| HP:0100575 | Neoplasm of the gallbladder | |
Run the differential on the 2 obligate / very frequent terms
Annotation source: 20301509[PMID]_25987178[PMID]_20571983[PMID]
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Sources for this card
- Orphanet page: orpha.net/en/disease/detail/512
- This record as JSON: /data/d/512.json