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Novel pathogenic variants in GBE1 causing fetal akinesia deformation sequence and severe neuromuscular form of glycogen storage disease type IV

Radhakrishnan, Periyasamya; Moirangthem, Amitaa; Nayak, Shalini S.a; Shukla, Anjua; Mathew, Maryb; Girisha, Katta M.a

doi: 10.1097/MCD.0000000000000248

Glycogen storage disease IV (GSD IV), caused by a defect in GBE1, is a clinically heterogeneous disorder. A classical hepatic form and a neuromuscular form have been described. The severe neuromuscular form presents as a fetal akinesia deformation sequence or a congenital subtype. We ascertained three unrelated families with fetuses/neonates who presented with fetal akinesia deformation sequence to our clinic for genetic counseling. We performed a detailed clinical evaluation, exome sequencing, and histopathology examination of two fetuses and two neonates from three unrelated families presenting with these perinatally lethal neuromuscular forms of GSD IV. Exome sequencing in the affected fetuses/neonates identified four novel pathogenic variants (c.1459G>T, c.144-1G>A, c.1680C>G, and c.1843G>C) in GBE1 (NM_000158). Histopathology examination of tissues from the affected fetuses/neonate was consistent with the diagnosis. Here, we add three more families with the severe perinatally lethal neuromuscular forms of GSD IV to the GBE1 mutation spectrum.

Departments of aMedical Genetics

bPathology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, India

Correspondence to Katta M. Girisha, MD, DM, Department of Medical Genetics, Kasturba Medical College, Manipal Academy of Higher Education, Manipal 576104, India Tel: +91 820 292 2636; fax: +91 820 257 1934; e-mail:

Received August 1, 2018

Accepted September 6, 2018

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