[MIM 615 273]

(NGLY1 deficiency, NGLY1-CDDG)

Very rare: 1/1.106. Autosomal recessive transmission of a pathogenic mutation of the NGLY1 gene (3p24.2) coding for N-glycanase. This mutation causes a dysfunction of the deglycosylation of the proteins.

The NGLY1 gene is also involved in the regulation of the mitochondrial activity by NFE2L1 and in the regulation of aquaporins.

Clinical presentation:

-        developmental retardation, hypotonia

-        alacrima (or shortage of tears): conjunctivitis, corneal abscess, corneal opacities

-        involuntary movements

-        abnormal eye movements

-        treatment-resistant epilepsy

-        microcephaly

-        small hands and feet

-        high  levels of hepatic enzymes, sometimes hyperlactatemia; liver biopsy shows accumulation of vacuoles in the cytoplasm

Anesthetic implications: 

refractory epilepsy, eye protection; neurologists recommend taking the same precautions as in case of mitochondrial cytopathy (see this term)

References : 

-        Lam C, Ferreira C, Krasnewich D, Toro C, Latham L et al. 
Prospective phenotyping of NGLY1-CDDG, the first congenital disorder of deglycosylation. 
Genet Med 2017; 19: 160-8.

Updated: August 2020