No abstract

Glycogen storage disorder type III (GSDIII) is a rare inborn error of metabolism due to loss of glycogen debranching enzyme activity, causing inability to fully mobilize glycogen stores and its consequent accumulation in various tissues, notably liver, cardiac and skeletal muscle. In the pediatric population, it classically presents as hepatomegaly with or without ketotic hypoglycemia and failure to thrive. In the adult population, it should also be considered in the differential diagnosis of left ventricular hypertrophy or hypertrophic cardiomyopathy, myopathy, exercise intolerance, as well as liver cirrhosis or fibrosis with subsequent liver failure. In this review article, we first present an overview of the biochemical and clinical aspects of GSDIII. We then focus on the recent findings regarding cardiac and neuromuscular impairment associated with the disease. We review new insights into the pathophysiology and clinical picture of this disorder, including symptomatology, imaging and electrophysiology. Finally, we discuss current and upcoming treatment strategies such as gene therapy aimed at the replacement of the malfunctioning enzyme to provide a stable and long‐term therapeutic option for this debilitating disease.

BackgroundRecreational use of nitrous oxide (N2O) has dramatically increased in recent years, resulting in numerous cases of acute sensorimotor tetraparesis secondary to nitrous oxide‐induced neuropathy (N2On). Challenging clinical features can mimic Guillain‐Barré syndrome (GBS), the main differential diagnosis upon admission. The most sensitive biomarkers for distinguishing between these two conditions remain to be determined.MethodsFifty‐eight N2On patients from three referral centers were retrospectively included over a 2‐year period and compared to GBS patients hospitalized during the same timeframe (47 patients). Collected demographic, clinical, biological, and electrophysiological data were compared between the two groups.ResultsThe typical N2On clinical pattern included distal sensorimotor deficit in lower limbs with absent reflexes, proprioceptive ataxia, and no cranial involvement (56.7% of our cohort). Misleading GBS‐like presentations were found in 14 N2On patients (24.1%), and 13 patients (22.4%) did not report N2O use during initial interview. Only half the N2On patients presented with reduced vitamin B12 serum levels upon admission. A slightly increased cut‐off (<200 pmol/L) demonstrated 85.1% sensitivity and 84.5% specificity in distinguishing N2On from GBS. Only 6.9% of N2On patients met the criteria for primary demyelination (p < 0.01), with only one presenting conduction blocks. A diagnostic algorithm combining these two biomarkers successfully classified all GBS‐like N2On patients.ConclusionsVitamin B12 serum level < 200 pmol/L cut‐off and conduction blocks in initial electrophysiological study are the two most sensitive biomarkers for rapidly distinguishing N2On from GBS patients. These two parameters are particularly useful in clinically atypical N2On with GBS‐like presentation.