Neuromuscular Involvement in Glycogen Storage Disease Type III in Fifty Tunisian Patients: Phenotype and Natural History in Young Patients

Abstract

Background Our aim was to describe the natural history of neuromuscular involvement (NMI) in glycogen storage disease type III (GSDIII). Methods We conducted a longitudinal study of 50 Tunisian patients, 9.87 years old in average. Results NMI was diagnosed at an average age of 2.66 years and was clinically overt in 85% of patients. Patients with clinical features were older (p = 0.001). Complaints were dominated by exercise intolerance (80%), noticed at 5.33 years in average. Physical signs, observed at 6.75 years in average, were dominated by muscle weakness (62%). Functional impairment was observed in 64% of patients, without any link with age (p = 0.255). Among 33 patients, 7 improved. Creatine kinase (CK) and aspartate aminotransferase (AST) levels were higher with age.Electrophysiological abnormalities, diagnosed in average at 6.5 years, were more frequent after the first decade (p = 0.0005). Myogenic pattern was predominant (42%). Nerve conduction velocities were slow in two patients. Lower caloric intake was associated with more frequent clinical and electrophysiological features. Higher protein intake was related to fewer complaints and physical anomalies. Conclusion Neuromuscular investigation is warranted even in asymptomatic patients, as early as the diagnosis of GSDIII is suspected. Muscle involvement can be disabling even in children. Favorable evolution is possible in case of optimal diet.

The Novel Compound Heterozygous Mutations in the AGL Gene in a Chinese Family With Adult Late-Onset Glycogen Storage Disease Type IIIa

“…This causes glycogen accumulation in the liver, skeletal muscle, and myocardium, resulting in liver enlargement, fasting hypoglycemia, delayed normal growth, and progressive muscle weakness (1). GSD IIIa is mostly diagnosed in infants and during early childhood; late-onset GSD IIIa in middle age is relatively rare (2). This study reported a patient aged 40 years who was diagnosed as GSD IIIa by muscle biopsy.…”

Glycogen storage diseases: An update

“…The median age of onset of CK elevation was reported to be 10 years[ 170 ]. Although muscle involvement becomes clinically more obvious later in life, mild muscle weakness on physical examination, motor developmental delay (delayed sitting, delayed standing upright, delayed onset of walking), exercise intolerance, and hypotonia were reported in the majority of pediatric patients with GSD-III[ 174 - 176 ]. Muscle weakness and wasting may slowly progress and become severe by the third or fourth decade of life[ 165 , 173 ].…”

“…Myopathy can be proximal, distal, or more generalized. Exercise intolerance with muscle fatigue, cramps and pain are evident in more than half of patients[ 170 , 174 , 175 ]. Bulbar or respiratory dysfunctions are rarely seen in GSD-III patients while no clinical involvement of facial or ocular muscles has been described in the literature[ 178 ].…”

French recommendations for the management of glycogen storage disease type III

“…The possible coexistence of peripheral nerves involvement remains debated, and is suggested in adult patients presenting distal muscular weakness [ 38 – 41 ]. This distal muscular weakness is probably the consequence of distal myopathy, and a recent study of a series of 16 patients, who all underwent an ENMG following the standard protocol, did not show any sign of peripheral nerve damage [ 42 ].…”