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Research Article: An Unusual Case of Neonatal Hypotonia and Femur Fracture: Neuromuscular Variant of Glycogen Storage Disease Type IV

Date Published: 2023-08-11

Abstract:
Glycogen storage disease type IV (GSD IV) (OMIM #232500) is an autosomal recessive disorder caused by deficiency of the glycogen-branching enzyme. Here, we report a patient presenting with prematurity and severe hypotonia resulting from a complicated pregnancy with polyhydramnios. During her stay in the neonatal unit, the infant remained dependent on a ventilator, and her movements were mostly absent, except for occasional small movements of her fingers. A spontaneous fracture of femur shaft occurred in the postnatal fourth week. Whole-exome sequencing of DNA from the patient revealed a homozygous missense variant in the GBE1 gene (c.1693C>T, p.Arg565Trp). The variation detected in the index case was also confirmed by Sanger sequencing in the patient and respective parents. This study showed that the neuromuscular subtypes of GSD-IV should be considered as a possible differential diagnosis in severe neonatal hypotonia cases.

Introduction:
Glycogen storage disease type IV (GSD-IV) (OMIM #232500) is a rare autosomal recessive inherited inborn error of carbohydrate metabolism caused by pathogenic variants in the GBE1 gene. This gene encodes the glycogen-branching enzyme (GBE) that is responsible for adding branches to glycogen molecules. Mutations in the GBE lead to the formation of abnormal glycogen molecules. This abnormal polysaccharide molecules display poor solubility and tend to accumulate in various tissues, predominantly in the liver and…

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