Early and lethal neurodegeneration with myasthenic and myopathic features: A new ALG14-CDG.
Neurology
; 89(7): 657-664, 2017 Aug 15.
Article
in En
| MEDLINE
| ID: mdl-28733338
ABSTRACT
OBJECTIVE:
To describe the presentation and identify the cause of a new clinical phenotype, characterized by early severe neurodegeneration with myopathic and myasthenic features.METHODS:
This case study of 5 patients from 3 families includes clinical phenotype, serial MRI, electrophysiologic testing, muscle biopsy, and full autopsy. Genetic workup included whole exome sequencing and segregation analysis of the likely causal mutation.RESULTS:
All 5 patients showed severe muscular hypotonia, progressive cerebral atrophy, and therapy-refractory epilepsy. Three patients had congenital contractures. All patients died during their first year of life. In 2 of our patients, electrophysiologic testing showed abnormal decrement, but treatment with pyridostigmine led only to temporary improvement. Causative mutations in ALG14 were identified in all patients. The mutation c.220 G>A (p.Asp74Asn) was homozygous in 2 patients and heterozygous in the other 3 patients. Additional heterozygous mutations were c.422T>G (p.Val141Gly) and c.326G>A (p.Arg109Gln). In all cases, parents were found to be heterozygous carriers. None of the identified variants has been described previously.CONCLUSIONS:
We report a genetic syndrome combining myasthenic features and severe neurodegeneration with therapy-refractory epilepsy. The underlying cause is a glycosylation defect due to mutations in ALG14. These cases broaden the phenotypic spectrum associated with ALG14 congenital disorders of glycosylation as previously only isolated myasthenia has been described.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
N-Acetylglucosaminyltransferases
/
Muscle Weakness
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Congenital Disorders of Glycosylation
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Epilepsy
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Cerebrum
Type of study:
Prognostic_studies
Limits:
Female
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Humans
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Infant
/
Male
Language:
En
Journal:
Neurology
Year:
2017
Document type:
Article