Researchers at Duke University have published a paper that sheds light on the relationship between APBD and Glycogen Storage Disease Type IV (GSD IV) in the scientific journal JCI Insight
Since the 1980s, the medical community has known that the enzyme which is deficient in APBD — glycogen branching enzyme — is also responsible for another disorder, GSD-IV. Unlike APBD which is an adult-onset disease, GSD IV typically presents in childhood, usually with some combination of liver, muscular, and/or cardiac disease. For decades, APBD and GSD IV have been thought to represent two distinct diseases with a shared genetic basis. This paper sheds new light on the relationship between GSD IV and APBD, showing that there may be more overlap between these two disorders than was previously suspected.
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Dr. Bridget Kiely (left) and Dr. Rebecca Koch (right)
The lead authors of the study, Dr. Rebecca Koch and Dr. Bridget Kiely, conducted the study under the guidance of senior author Dr. Priya Kishnani at Duke University Medical Center, in collaboration with a multi-national group of researchers and clinicians from three continents.
The study utilized a comparative approach involving both patients and a mouse model. Their analysis included long-term clinical and genetic data from patients who were diagnosed with GSDIV during childhood, in addition to data from a mouse model that had mutations in the same gene (GBE1) that causes APBD and GSD IV in humans. The researchers uncovered several pieces of evidence suggesting that there is significant overlap between the manifestations of APBD and GSDIV.
First, when they carefully analyzed the characteristics of the mice with GBE1 mutations, they found that they showed signs of both APBD (including neurological symptoms such as gait dysfunction) and GSD IV (including elevated liver enzymes and liver scarring). Second, their cohort of patients included one individual who initially came to medical attention during childhood for liver disease – diagnosed at that time as “non-progressive hepatic” GSD IV – and later went on to develop APBD as an adult. The researchers analyzed autopsy data from this patient, who died at age 47, and found that he still had evidence of liver scarring (consistent with GSD IV) at the time of his death.
Overall, these findings suggest that it may be more accurate to consider APBD and GSD IV as part of the same disease spectrum rather than distinct disorders. This means that some individuals who are diagnosed with GSD IV during childhood may be at risk for developing APBD later in life, while some individuals with APBD may have disease manifestations that have historically been considered part of GSD IV (e.g., liver disease and cardiomyopathy). This view aligns with clinical practice guidelines published in 2023, which emphasize the need for all patients with APBD/GSD-IV to receive care from a multi-disciplinary team.
Editor’s Note: “Research Highlights” is an ongoing feature in our newsletter. It is focused on scientific publications of interest to our community. Our thanks to Dr. Bridget Kiely and Dr. Rebecca Koch for sharing their research with us in the August 2024 edition of our e-newsletter!
