Unexplained death in patients with NGLY1 mutations may be explained by adrenal insufficiency.
Physiol Rep
; 7(3): e13979, 2019 02.
Article
em En
| MEDLINE
| ID: mdl-30740912
ABSTRACT
Homozygous mutations in NGLY1 were recently found to cause a condition characterized by a complex neurological syndrome, hypo- or alacrimia, and elevated liver transaminases. For yet unknown reasons, mortality is increased in patients with this condition. NGLY1 encodes the cytosolic enzyme N-glycanase 1, which is responsible for the deglycosylation of misfolded N-glycosylated proteins. Disruption of this process is hypothesized to lead to an accumulation of misfolded proteins in the cytosol. Here, we describe the disease course of a girl with a homozygous mutation in NGLY1, namely c.1837del (p.Gln613 fs). In addition to the previously described symptoms, at the age of 8 she presented with recurrent infections and hyperpigmentation, and, subsequently, a diagnosis of primary adrenal insufficiency was made. There are no previous reports describing adrenal insufficiency in such patients. We postulate that patients with NGLY1 deficiency may develop adrenal insufficiency as a consequence of impaired proteostasis, and the accompanying proteotoxic stress-induced cell death, through defective Nrf1 function. We recommend an annual evaluation of adrenal function in all patients with NGLY1 mutations in order to prevent unnecessary deaths.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Insuficiência Adrenal
/
Defeitos Congênitos da Glicosilação
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Peptídeo-N4-(N-acetil-beta-glucosaminil) Asparagina Amidase
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Deficiências na Proteostase
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Proteostase
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Mutação
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Child
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Female
/
Humans
Idioma:
En
Revista:
Physiol Rep
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Holanda