Diabetes Does Not Explain It All

The patient was referred for further evaluation of vision loss and unsteady gait. Neuro-psychological testing found moderate difficulties in memory and executive function. Based on the history of a bladder and erectile dysfunction, sensory neuropathy and neuro-imaging demonstrating atrophy with characteristics of a leukodystrophy, further diagnostic testing was performed. Genetic testing for the glycogen branching enzyme 1 (GBE1) detected a heterozygous mutation, and a functional enzymatic activity assay confirmed dysfunction of glycogen branching enzyme 1. He was enrolled in a clinical trial of trihetanoin, an odd-carbon fatty acids, that is theorized to provide substrate to the citric acid cycle there by correcting the underlying energy deficit caused by the enzyme abnormality. APBD is a progressive disorder characterized by a neurogenic bladder, progressive gait disorder, sensory loss in the lower extremities, and cognitive decline. However, vision loss with optic atrophy has been rarely associated with APBD. Imaging with MRI typically shows medullary and spinal atrophy, with hyperintense white matter abnormalities. The disease typically present in the 4th or 5th decade. There is pathologic accumulation of intracellular polyglucosan bodies in cells of peripheral nerves and central nervous system. It is also hypothesized that decreased glycogen degradation leads to energy deficit and further dysfunction. Almost a third of the known cases of APBD are heterozygous with an assumed additional, but unidentified, second mutation.