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Polish Journal of Pathology
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Short communication

Liver involvement in NGLY1 congenital disorder of deglycosylation

Patryk Lipiński
,
Joanna Cielecka-Kuszyk
,
Piotr Socha
,
Anna Tylki-Szymańska

Pol J Pathol 2020; 71 (1): 1-3
Online publish date: 2020/02/25
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N-glycanase 1 (NGLY1) deficiency is a congenital disorder of deglycosylation (NGLY1-CDDG) and since its first report in 2012, 27 patients have been described [1, 2, 3]. All but one were diagnosed by exome or genome sequencing; the remaining one was identified by finding an increased concentration of a urinary marker [4, 5, 6, 7, 8, 9, 10, 11, 12].
The aim of this study was to describe the liver phenotype of a Polish patient diagnosed with NGLY1-CDDG and to provide an overview of the literature in regard of hepatic presentation.
Liver biopsy was performed in some of the reported patients showing a cytoplasmic storage of amorphous material (with staining properties similar to glycogen) or vacuolization in hepatocytes consistent with storage [4]. Heeley et al. reported on a patient in whom liver biopsy performed at 6 months of age showed features of liver cirrhosis [5]. One of the patients described by Lam et al. underwent orthotopic liver transplantation at 21 months of age for liver cirrhosis and presumed hepatocellular carcinoma [7].
Our patient presented with global developmental delay, hyperkinetic movement disorder and hypolacrimia since infancy. Epilepsy was diagnosed at the age of 2 years with normal results of brain magnetic resonance imaging. Elevated serum transaminases were first (incidentally) noted at 10 months of age (ALT > AST, results 3-5 times upper limit of normal range). Liver biopsy done at the age of 3 years revealed moderate micro- as well as macro-vesicular steatosis and minimal lobular fibrosis (Figure 1). The presence of an amorphous periodic acid-Schiff staining positive diastases-digested material in the cytoplasm was also noted. At the last follow-up (7 years of age) serum transaminases were normal with the presence of normal liver volumetry but hyperechoic liver parenchyma (indicative of steatosis) on abdominal ultrasound. Whole exome sequencing revealed the patient to be a compound heterozygous for two unreported variants c.1789+1G>A and c.1063T>C in the NGLY1 gene. The parents were carriers of these variants.
Literature review revealed global developmental disability in all reported patients, and hyperkinetic movements as well as alacrima/hypolacrima in nearly all. In the great majority of patients, serum transaminases were increased. In our recently published paper, we proposed that NGLY1-CDDG should be considered in patients with developmental disability associated with a hyperkinetic movement disorder and alacrimia/hypolacrima [3]. Absence of the latter two symptoms does not rule out this diagnosis.
The presence of cytoplasmic storage of amorphous periodic acid-Schiff staining positive diastases-digested material reflects the storage of misfolded probably not degraded N-glycosylated proteins. NGLY1 deficiency should be added to the list of disorders presenting with liver steatosis as well as fibrosis or even cirrhosis.

The authors declare no conflict of interest.

References

1. Lam C, Wolfe L, Need A, et al. NGLY1-Related Congenital Disorder of Deglycosylation. In: Adam MP, Ardinger HH, Pagon RA, et al. (eds.). GeneReviews® [Internet]. University of Washington, Seattle 1993-2019.
2. Need AC, Shashi V, Hitomi Y, et al. Clinical application of exome sequencing in undiagnosed genetic conditions. J Med Genet 2012; 49: 353-361.
3. Lipiñski P, Bogdañska A, Ró¿d¿yñska-Œwi¹tkowska A, et al. NGLY1 deficiency: Novel patient, review of the literature and diagnostic algorithm. JIMD Rep 2019 (in press). https://doi.org/10.1002/jmd2.12086.
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Address for correspondence

Prof. Anna Tylki-Szymañska
Department of Pediatrics, Nutrition and Metabolic Diseases
The Children’s Memorial Health Institute
Al. Dzieci Polskich 20
04-730 Warsaw, Poland
Copyright: © 2020 Polish Association of Pathologists and the Polish Branch of the International Academy of Pathology This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License (http://creativecommons.org/licenses/by-nc-sa/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
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