APBD: An Adult-Onset Form of GSD IV

May 15, 2021

Editor’s Note: This article was featured in “The Ray” (volume 44, issue 4 / Winter 2021) published by the Association for Glycogen Storage Disease.

What is APBD?

Adult Polyglucosan Body Disease (APBD) is a neuromuscular, adult-onset form of glycogen storage disease type IV (GSD IV).

The Symptoms of APBD

APBD symptoms include numbness and tingling in feet/legs and hands/arms (peripheral neuropathy), progressive muscle weakness and stiffness (spasticity), increasing difficulty starting or stopping the flow of urine (neurogenic bladder), fatigue, and cognitive difficulties.

Individuals with APBD can begin experiencing symptoms as early as age 35. They eventually lose the ability to walk, stand, stay continent, stay awake, perform at work, and socialize. They are robbed of nearly every aspect of their independent adult lives.

APBD is pan-ethnic, but is diagnosed most frequently in people of Ashkenazi Jewish ancestry. It is frequently misdiagnosed as multiple sclerosis, cerebral small vessel disease, amyotrophic lateral sclerosis, or peripheral neuropathies.

APBD is a Single-Gene Disease

APBD is one of several forms of GSD IV, all of which are caused by autosomal recessive mutations in the glycogen branching enzyme (GBE1) gene. The glycogen branching enzyme helps build well-branched sugar storage molecules called glycogen. Insufficient levels of the enzyme result in the accumulation of poorly branched glycogen. This poorly branched glycogen forms clumps called polyglucosan bodies that build up in muscle, nerve, and various other tissues in the body and drive APBD progression.

Get research news updates from us!

    Sign up for Updates:

    APBD is the Adult-Onset Form of GSD IV

    While GSD IV is caused by mutations in only one gene (GBE1), its clinical presentation spans a wide continuum. A recent publication, led by Dr. Paulo Victor Sgobbi Souza at the Federal University of São Paulo titled “GBE1-related disorders: Adult polyglucosan body disease and its neuromuscular phenotypes,” describes the diverse GSD IV clinical presentations:

    • Fatal Perinatal Neuromuscular
      Perinatal-onset. Fetal hypokinesia and hydrops, severe hypotonia, amyotrophy; neonatal death
    • Congenital Neuromuscular
      Neonatal-onset. Severe hypotonia, dilated cardiomyopathy, respiratory failure; early infancy death
    • Classic (progressive) Hepatic
      Infancy-onset. Hepatomegaly, liver failure and cirrhosis, mild to moderate hypotonia, cardiomyopathy; infancy or childhood death
    • Non-progressive Hepatic
      Childhood-onset. Hepatopathy, early hypotonia, myopathy
    • Childhood Neuromuscular
      Childhood-onset. Progressive limb-girdle muscular weakness, dilated cardiomyopathy
    • Adult Polyglucosan Body Disease
      Adult-onset (>35 years). Ashkenazi Jewish and other ethnicities. Neurogenic bladder, spastic paraparesis, orthostatic hypotension, painful sensitive axonal neuropathy, lower motor neuron syndrome, constipation, cognitive decline

    Raising Awareness of the GSD IV Continuum

    The reason why different mutations in GBE1 lead to such varied forms of GSD IV remains unclear. Improved awareness of the forms of GSD IV is important to reduce the rate of misdiagnoses and to ensure appropriate care is provided. Such care should be multidisciplinary and, depending on the GSD IV form, include specialists in hepatology, cardiology, neurology, urology, nutrition, medical genetics, and physical therapy. There are presently no targeted treatments available for GSD IV. However, researchers are making progress towards the development of gene and small molecule therapies for GSD IV.

    Get research news updates from us!

      Sign up for Updates: