ORPHA:404454
Alacrimia-choreoathetosis-liver dysfunction syndrome
Synonyms: NGLY1 deficiency · NGLY1-CDDG
- Type
- Disease
- Group
- Disorder
- Inheritance
- Autosomal recessive
- Age of onset
- Infancy, Neonatal
- Status
- active
A rare, genetic, inborn error of metabolism disorder characterized by global developmental delay, hypotonia, choreoathetosis, hypo-/alacrimia, and liver dysfunction which manifests with elevated liver transaminases and hepatocyte cytoplasmic storage material or vacuolization on liver biopsy. Additional features reported include acquired microcephaly, hypo-/areflexia, seizures, peripheral neuropathy, intellectual and language/speech disability, additional ocular anomalies and EEG and brain imaging abnomalities.
1
Names in Orphadata languages
12 of 12 languages| Lang | Name | Synonyms |
|---|---|---|
| en | Alacrimia-choreoathetosis-liver dysfunction syndrome | NGLY1 deficiency · NGLY1-CDDG |
| fr | Syndrome d'alacrymie-choréoathétose-hépatopathie | Déficit en NGLY1 · NGLY1-CDDG |
| de | Alakrimie-Choreoathetose-Leberdysfunktion-Syndrom | NGLY1-CDDG · NGLY1-Mangel |
| es | Síndrome de alacrimia-coreoatetosis-disfunción hepática | Deficiencia de NGLY1 · NGLY1-CDDG |
| it | Sindrome da alacrimia, coreoatetosi e disfunzione epatica | Deficit di NGLY1 · NGLY1-CDDG |
| nl | Alacrimie - choreoathetose - leverdisfunctie-syndroom | NGLY1-CDDG · NGLY1-deficiëntie |
| pt | Síndrome de alacrimia - coreoatetose - disfunção hepática | |
| pl | Zespół braku łez, choreoatetozy i dysfunkcji wątroby | NGLY1-CDDG · Niedobór NGLY1 |
| cs | Syndrom zahrnující alakrimii, choreoatetózu a dysfukci jater | Deficit NGLY1 · NGLY1-CDDG |
| uk | Синдром алакрімії-хореоатетозу-печінкової дисфункції | Дефіцит NGLY1 · NGLY1-CDDG |
| zh | 无泪-舞蹈手足徐动症-肝功能障碍综合征 | NGLY1缺乏 |
| tr | Alakrimia-koreoatetoz-karaciğer disfonksiyon sendromu | NGLY1-CDDG · NGLY1 deksikliği |
Definition in:
2
Cross-references
qualifier = Orphanet mapping relation| Source | Code | Qualifier | ICD relation | Validation |
|---|---|---|---|---|
| OMIM | 615273 | E | validated | |
| ICD-10 | E77.8 | NTBT | attributed | validated |
| ICD-11 | 5C54.Y | NTBT | attributed | validated |
| MONDO | 0800044 | E | validated | |
| MeSH | C000626124 | E | validated | |
| UMLS | C3808991 | E | validated | |
| GARD | 12315 | E | validated |
E exact · NTBT this ORPHAcode is narrower than the target · BTNT broader than the target · ND not decided.
3
Classification
Preferential parent (Orphanet linearisation):
Parents in the classifications (6):
- ORPHA:281244Autosomal ichthyosis syndrome with other associated signs
rare genetic diseases; rare skin diseases - ORPHA:98604Congenital alacrima
rare genetic diseases; rare ophthalmic disorders - ORPHA:183484Genetic subcutaneous tissue disorder
rare genetic diseases - ORPHA:91088Other metabolic disease
rare inborn errors of metabolism; rare genetic diseases - ORPHA:611314Rare syndromic intellectual disability without multiple congenital anomalies/dysmorphic syndrome
rare genetic diseases; rare neurological diseases - ORPHA:79382Subcutaneous tissue disease
rare skin diseases
No children.
4
Genes
1 direct| Gene | Association | Status | HGNC | Ensembl | OMIM | Locus | Name | Source of validation |
|---|---|---|---|---|---|---|---|---|
| NGLY1 | Disease-causing germline mutation(s) (loss of function) in | Assessed | HGNC:17646 | ENSG00000151092 | 610661 | 3p24.2 | N-glycanase 1 | 24651605[PMID] |
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Prevalence and incidence
2 records| Type | Class | Value | Area | Qualification | Validation | Source |
|---|---|---|---|---|---|---|
| Cases/families | 8 cases | Worldwide | Case(s) | Validated | 24651605[PMID]_22581936[PMID] | |
| Point prevalence | <1 / 1 000 000 | — | Worldwide | Class only | Validated | ORPHANET_24651605[PMID]_22581936[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
91 annotations · validated 2019-07-12| HPO | Term (as annotated by Orphanet) | Diagnostic |
|---|---|---|
| Very frequent (99-80%) | ||
| HP:0002059 | Cerebral atrophy | |
| HP:0002487 | Hyperkinetic movements | |
| HP:0007141 | Sensorimotor neuropathy | |
| Frequent (79-30%) | ||
| HP:0012447 | Abnormal myelination | |
| HP:0001344 | Absent speech | |
| HP:0000522 | Alacrima | |
| HP:0001272 | Cerebellar atrophy | |
| HP:0001266 | Choreoathetosis | |
| HP:0012450 | Chronic constipation | |
| HP:0025455 | Decreased CSF 5-hydroxyindolacetic acid concentration | |
| HP:0025458 | Decreased CSF albumin | |
| HP:0040209 | Decreased CSF biopterin level | |
| HP:0003785 | Decreased CSF homovanillic acid concentration | |
| HP:0025457 | Decreased CSF protein | |
| HP:0003563 | Decreased LDL cholesterol concentration | |
| HP:0000633 | Decreased lacrimation | |
| HP:0002376 | Developmental regression | |
| HP:0002353 | EEG abnormality | |
| HP:0002910 | Elevated circulating hepatic transaminase concentration | |
| HP:0001508 | Failure to thrive | |
| HP:0002123 | Generalized myoclonic seizure | |
| HP:0001263 | Global developmental delay | |
| HP:0012153 | Hypotriglyceridemia | |
| HP:0002540 | Inability to walk | |
| HP:0002659 | Increased susceptibility to fractures | |
| HP:0001249 | Intellectual disability | |
| HP:0002187 | Intellectual disability, profound | |
| HP:0002870 | Obstructive sleep apnea | |
| HP:0002465 | Poor speech | |
| HP:0001518 | Small for gestational age | |
| Occasional (29-5%) | ||
| HP:0001771 | Achilles tendon contracture | |
| HP:0003086 | Acromesomelia | |
| HP:0002345 | Action tremor | |
| HP:0020037 | Astasia | |
| HP:0002305 | Athetosis | |
| HP:0010819 | Atonic seizure | |
| HP:0003447 | Axonal loss | |
| HP:0002072 | Chorea | |
| HP:0001374 | Congenital hip dislocation | |
| HP:0000559 | Corneal scarring | |
| HP:0002673 | Coxa valga | |
| HP:0012340 | Decreased resting energy expenditure | |
| HP:0025336 | Delayed ability to sit | |
| HP:0012448 | Delayed myelination | |
| HP:0002750 | Delayed skeletal maturation | |
| HP:0001332 | Dystonia | |
| HP:0000297 | Facial hypotonia | |
| HP:0030194 | Fatigable weakness of speech muscles | |
| HP:0010821 | Focal emotional seizure with laughing | |
| HP:0011167 | Focal tonic seizure | |
| HP:0002909 | Generalized aminoaciduria | |
| HP:0002121 | Generalized non-motor (absence) seizure | |
| HP:0002171 | Gliosis | |
| HP:0002240 | Hepatomegaly | |
| HP:0001385 | Hip dysplasia | |
| HP:0011900 | Hypofibrinogenemia | |
| HP:0001265 | Hyporeflexia | |
| HP:0031146 | Impaired oral bolus formation | |
| HP:0031162 | Impaired oropharyngeal swallow response | |
| HP:0012469 | Infantile spasms | |
| HP:0001382 | Joint hypermobility | |
| HP:0003121 | Limb joint contracture | |
| HP:0031008 | Lingual dystonia | |
| HP:0001413 | Micronodular cirrhosis | |
| HP:0001414 | Microvesicular hepatic steatosis | |
| HP:0001336 | Myoclonus | |
| HP:0011954 | Nodular regenerative hyperplasia of liver | |
| HP:0000657 | Oculomotor apraxia | |
| HP:0002421 | Poor head control | |
| HP:0008151 | Prolonged prothrombin time | |
| HP:0002205 | Recurrent respiratory infections | |
| HP:0004349 | Reduced bone mineral density | |
| HP:0001929 | Reduced factor XI activity | |
| HP:0005543 | Reduced protein C activity | |
| HP:0100899 | Sclerosis of finger phalanx | |
| HP:0002650 | Scoliosis | |
| HP:0005484 | Secondary microcephaly | |
| HP:0003834 | Shoulder dislocation | |
| HP:0001744 | Splenomegaly | |
| HP:0025401 | Staring gaze | |
| HP:0030906 | Suck reflex | |
| HP:0031051 | Tarsal sclerosis | |
| HP:0002119 | Ventriculomegaly | |
| Very rare (<4-1%) | ||
| HP:0001488 | Bilateral ptosis | |
| HP:0000548 | Cone/cone-rod dystrophy | |
| HP:0011496 | Corneal neovascularization | |
| HP:0000577 | Exotropia | |
| HP:0030001 | Lagophthalmos | |
| HP:0000648 | Optic atrophy | |
| HP:0000543 | Optic disc pallor | |
| HP:0000580 | Pigmentary retinopathy | |
Run the differential on the 3 obligate / very frequent terms
Annotation source: 31217022[PMID]_27388694[PMID]_24651605[PMID]_29419975[PMID]
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Sources for this card
- Orphanet page: orpha.net/en/disease/detail/404454
- This record as JSON: /data/d/404454.json