The GBE1 structure reveals a conserved amylase core that houses the active centre for the branching reaction and harbours almost all GSDIV and APBD mutations.
Therefore, we performed additional investigations that eventually led to the diagnosis of adult polyglucosan body disease caused by two novel missense mutations (p.Asp413His and p.Gly534Val) in the glycogen branching enzyme gene.
GBE1 mutations can cause an early adult-onset relapsing-remitting form of polyglucosan body disease distinct from adult polyglucosan body disease in several ways, including younger age at onset, history of infantile liver involvement, and subacute and remitting course simulating multiple sclerosis.
To test the suspected pathogenicity of polyglucosans in neurological glycogenoses, we have modeled the typical glycogenosis Adult Polyglucosan Body Disease (APBD) by suppressing glycogen branching enzyme 1 (GBE1, EC 2.4.1.18) expression using lentiviruses harboring short hairpin RNA (shRNA).
APBD with GBE deficiency, with occasional exceptions, is a clinically homogenous disorder that should be suspected in patients with adult onset leukodystrophy or spastic paraplegia with early onset of urinary symptoms and spinal atrophy.
Our findings widen the spectrum of APBD genotypes, underline the importance of performing GBE analysis in all APBD patients, and suggest that brain white matter degeneration in APBD may result from tissue damage involving axons and myelin.
Autopsy of a 50-year-old woman with adult polyglucosan body disease and missense mutations (Arg515His, Arg524Gln) in the glycogen branching enzyme gene (GBE) revealed accumulation of polyglucosan bodies in the heart, brain, and nerve.
This is the first identification of GBE mutations underlying adult polyglucosan body disease in a non-Ashkenazi family, and confirms that adult glycogen storage disease type IV can manifest clinically as adult polyglucosan body disease.
This is the first identification of GBE mutations underlying adult polyglucosan body disease in a non-Ashkenazi family, and confirms that adult glycogen storage disease type IV can manifest clinically as adult polyglucosan body disease.
This is the first identification of GBE mutations underlying adult polyglucosan body disease in a non-Ashkenazi family, and confirms that adult glycogen storage disease type IV can manifest clinically as adult polyglucosan body disease.
As this mutation was previously identified in a nonprogressive form of GSD IV and was shown in expression studies to result in a significant residual GBE activity, present findings explain the late onset and slowly progressive course of APBD in our patients.