A Novel Mutation in a Newborn Baby Leading to Glycogen Storage Disease Type Ia

Area of Science:

• Genetics
• Biochemistry
• Pediatrics

Background:

• Glycogen storage disease type Ia (GSD1A) is a rare genetic metabolic disorder.
• It results from mutations in the Glucose-6-phosphatase (G6PC) gene, affecting glucose metabolism.
• Hepatomegaly is a common clinical manifestation in GSD1A patients.

Purpose of the Study:

• To report a case of GSD1A in a neonate with a novel G6PC gene mutation.
• To characterize the clinical presentation of GSD1A associated with this new mutation.
• To expand the understanding of GSD1A genetic and clinical spectrum.

Main Methods:

• Clinical assessment of a 23-day-old female infant presenting with respiratory distress, hypoglycemia, lactic academia, hyperlipidemia, and hyperuricemia.
• Genetic analysis involving direct sequencing of the G6PC gene.
• Identification and characterization of a novel homozygous missense mutation (c.137T>G/p.Leu46Arg).

Main Results:

• A novel homozygous missense mutation, c.137T>G/p.Leu46Arg, in the G6PC gene was identified in the patient.
• The patient's parents were found to be heterozygotes for the identified variant.
• The patient exhibited typical GSD1A metabolic derangements but lacked early-onset hepatomegaly.

Conclusions:

• The novel homozygous G6PC mutation c.137T>G/p.Leu46Arg is causative of GSD1A.
• This case highlights a variant GSD1A presentation, notably the absence of early hepatomegaly.
• Findings broaden the spectrum of G6PC mutations and associated clinical phenotypes in GSD1A.