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Background <p>Glycogen storage disease type III (GSD III) is an autosomal recessive disorder caused by mutations in the AGL gene, leading to a deficiency of the glycogen debranching enzyme. It is characterized by heterogeneous clinical and genetic presentations, with limited data available from North Africa. In the present study, we report a novel AGL variant in GSD III.</p> Case summary <p>A 20-month-old boy presented with hepatomegaly, fasting hypoglycemia and elevated transaminases. Hepatic biopsy revealed hepatocyte enlargement with glycogen accumulation and a 12-hour urine sample analyzed by thin-layer chromatography revealed the tetrasaccharide (glucose)₄ excretion. Next-generation sequencing identified a novel nonsense variant in exon 31 of the <i>AGL</i> gene NM_000642.3:c.4223T &gt; A, p.(Leu1408*). This variant, absent from international databases, represents the first genetically confirmed GSD III case in Morocco. Despite dietary management, the patient developed respiratory distress and died before age three.</p> Discussion <p>This study outlines the genetic and phenotypic features of a Moroccan GSD III patient and describes a novel <i>AGL</i> variant that broadens the mutational spectrum. The severe outcome likely reflects the combination of its truncating nature, homozygous state, and critical location in exon 31, within the glycogen-binding domain. As reported, this association has been linked to early cardiomyopathy, poor dietary response, and increased risk of sudden death.</p> Conclusions <p>GSD III is underdiagnosed in Morocco, which is concerning, as patients with GSD III can achieve significant improvement with appropriate dietary management. Indeed, timely diagnosis and treatment, can greatly benefit patients and even lead to partial recovery and guide family screening and counseling.</p>

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Identification of a novel nonsense mutation in the AGL gene in glycogen storage disease type IIIa: first genetically confirmed case report from Morocco

  • 期刊论文

  • 发表日期：

    2025年12月13日

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  • Maroua Jakani,
  • Imane Assiri,
  • Sana El Foutat,
  • Samira Najeh,
  • Miloud Hammoud,
  • Abdelati Berrachid,
  • Karima Lafhal,
  • Es-said Sabir,
  • Khouloud Elmazi,
  • Mariam Lagrine,
  • Aicha Bourrahouat,
  • Naima Fdil

摘要

Background

Glycogen storage disease type III (GSD III) is an autosomal recessive disorder caused by mutations in the AGL gene, leading to a deficiency of the glycogen debranching enzyme. It is characterized by heterogeneous clinical and genetic presentations, with limited data available from North Africa. In the present study, we report a novel AGL variant in GSD III.

Case summary

A 20-month-old boy presented with hepatomegaly, fasting hypoglycemia and elevated transaminases. Hepatic biopsy revealed hepatocyte enlargement with glycogen accumulation and a 12-hour urine sample analyzed by thin-layer chromatography revealed the tetrasaccharide (glucose)₄ excretion. Next-generation sequencing identified a novel nonsense variant in exon 31 of the AGL gene NM_000642.3:c.4223T > A, p.(Leu1408*). This variant, absent from international databases, represents the first genetically confirmed GSD III case in Morocco. Despite dietary management, the patient developed respiratory distress and died before age three.

Discussion

This study outlines the genetic and phenotypic features of a Moroccan GSD III patient and describes a novel AGL variant that broadens the mutational spectrum. The severe outcome likely reflects the combination of its truncating nature, homozygous state, and critical location in exon 31, within the glycogen-binding domain. As reported, this association has been linked to early cardiomyopathy, poor dietary response, and increased risk of sudden death.

Conclusions

GSD III is underdiagnosed in Morocco, which is concerning, as patients with GSD III can achieve significant improvement with appropriate dietary management. Indeed, timely diagnosis and treatment, can greatly benefit patients and even lead to partial recovery and guide family screening and counseling.