2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-The Diagnostic Odyssey: A Review of Two Patients with Adult Polyglucosan Body Disease

Pdf Summary

Two women of Ashkenazi Jewish descent were diagnosed with Adult Polyglucosan Body Disease (APBD) after experiencing bladder dysfunction and urological difficulties for many years. They later developed neurological symptoms including unsteady gait, polyneuropathy, muscle weakness, memory loss, and abnormal eye movements. Brain and spinal imaging showed white matter changes, brain stem and spinal cord atrophy. Initial genetic testing did not detect any mutations, but subsequent reanalysis and whole genome sequencing revealed two pathogenic variants in the GBE1 gene, which codes for the glycogen branching enzyme responsible for glycogen synthesis. These variants, Y239S and a deep intronic variant, are the most common in APBD and are found disproportionately in the Ashkenazi Jewish population. Bladder dysfunction is often the earliest sign of APBD, appearing decades before other neurological symptoms. Screening for APBD may be successful in urology/urogynecology clinics, particularly in the Ashkenazi population. Early detection of urinary dysfunction as a marker for APBD may be critical for early therapeutic intervention. The diagnostic journey in these APBD patients highlights the importance of education on rare monogenic disorders in adults, especially in non-genetics clinical settings.

Asset Subtitle

Presenting Author - Anusha Ebrahim, BA; Co-Author - Daniel Benavides, BS; Co-Author - Camilo Toro, MD; Co-Author - Colleen Wahl, DNP, FNP-BC; Co-Author - William A. Gahl, MD, Ph.D;

Meta Tag

Brain/Nervous System

Genome sequencing

Genotype-Phenotype Correlations

Identification of Disease Genes

Natural History

Phenotypic delineation of disorders

Sequencing

Variant Detection

Co-Author Daniel Benavides, BS

Co-Author Camilo Toro, MD

Co-Author Colleen Wahl, DNP, FNP-BC

Co-Author William A. Gahl, MD, Ph.D

Presenting Author Anusha Ebrahim, BA

Keywords

Adult Polyglucosan Body Disease

bladder dysfunction

neurological symptoms

GBE1 gene

pathogenic variants

Ashkenazi Jewish population

urology

early detection

therapeutic intervention

rare monogenic disorders