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Case Reports
. 2023 Jun;191(6):1626-1631.
doi: 10.1002/ajmg.a.63179. Epub 2023 Mar 17.

Long-term outcomes in ALG13-Congenital Disorder of Glycosylation

Rameen Shah  1   2 , Christin Johnsen  1   3 , Beth A Pletcher  4 , Andrew C Edmondson  5 , Tamas Kozicz  1   6   7 , Eva Morava  1   6   8
Affiliations
Case Reports

Long-term outcomes in ALG13-Congenital Disorder of Glycosylation

Rameen Shah et al. Am J Med Genet A. 2023 Jun.

Abstract

ALG13-CDG is a rare X-linked disorder of N-linked glycosylation. Given the lack of long-term outcome data in ALG13-CDG, we collected natural history data and reviewed individuals surviving to young adulthood with confirmed pathogenic variants in ALG13 in our own cohort and in the literature. From the 14 ALG13-CDG patients enrolled into our Frontiers of Congenital Disorders of Glycosylation Consortium natural history study only two patients were older than 16 years; one of these two females is so far unreported. From the 52 patients described in the medical literature with confirmed pathogenic variants in ALG13 only five patients were older than 16 years (all females), in addition to the new, unreported patient from our natural history study. Two male patients have died due to ALG13-CDG, and there were no surviving males older than 16 years with a confirmed ALG13-CDG diagnosis. Our adolescent and young adult cohort of six patients presented with epilepsy, muscular hypotonia, speech, and developmental delay. Intellectual disability was present in all female patients with ALG13-CDG. Unreported features included ataxia, neuropathy, and severe gastrointestinal symptoms requiring G/J tube placement. In addition, two patients from our natural history study developed unilateral hearing loss. Skeletal abnormalities were found in four patients, including osteopenia and scoliosis. Major health problems included persistent seizures in three patients. Ketogenic diet was efficient for seizures in three out of four patients. Although all patients were mobile, they all had severe communication problems with mostly absent speech and were unable to function without parental support. In summary, long-term outcome in ALG13-CDG includes gastrointestinal and skeletal involvement in addition to a chronic, mostly non-progressive neurologic phenotype.

Keywords: ALG13-CDG; glycosylation; hearing loss; scoliosis; seizures; survival.

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Conflict of interest statement

Conflict of interest statement

Rameen Shah, Christin Johnsen, Beth A Pletcher, Andrew C. Edmondson, Tamas Kozicz and Eva Morava report no conflict of interest.

Figures

Figure 1:
Figure 1:
Patient 5 shows no significant dysmorphism . Note symmetric round face, hypertelorism.
See this image and copyright information in PMC

References

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