Neurological Characteristics of Pediatric Glycogen Storage Disease

Glycogen storage diseases (GSD) encompass a group of rare inherited diseases due dysfunction of glycogen metabolism. Hypoglycemia is the most common primary manifestation of GSD, and disturbances in glucose metabolism can cause neurological damage. The aims of this study were to first investigate the metabolic, genetic, and neurological profiles of children with GSD, and to test the hypothesis whether GSD type I would have greater neurological impact than GSD type IX. A cross-sectional study was conducted with 12 children diagnosed with GSD [Types: Ia (n=5); 1, Ib (n=1); 4, IXa (n=5); and 1, IXb (n=1)]. Genetic testing was conducted for the following genes using multigene panel analysis. The biochemical data and magnetic resonance imaging of the brain presented by the patients were evaluated. The criteria of adequate metabolic control were adopted based on the European Study on Glycogen Storage Disease type I consensus. Pathogenic mutations were identified using multigene panel analyses. The mutations and clinical chronology were related to the disease course and neuroimaging findings. Adequate metabolic control was achieved in 67% of patients (GSD I, 43%; GSD IX, 100%). Fourteen different mutations were detected, and only two co-occurring mutations were observed across families (G6PC c.247C>T and c.1039C>T). Six previously unreported variants were identified (5 PHKA2; 1 PHKB). The proportion of GSD IX was higher in our cohort compared to other studies. Brain imaging abnormalities were more frequent among patients with GSD I, early-symptom onset, longer hospitalization, and inadequate metabolic control. The frequency of mutations was similar to that observed among the North American and European populations. None of the mutations observed in PHKA2 have been described previously. Therefore, current study reports six GSD variants previously unknown, and neurological consequences of GSD I. The principal neurological impact of GSD appeared to be related to inadequate metabolic control, especially hypoglycemia.

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A high prevalence of low bone mineral density in children with glycogen storage disease type III

Archives of Medical Science ◽

10.5114/aoms/141986 ◽

2021 ◽

Author(s):

Engy Mogahed ◽

Mariam El-Moslemany ◽

Ihab Aboueleyoun ◽

Noha Musa ◽

Mohamed Abo-Elsoud ◽

...

Keyword(s):

Metabolic Control ◽

Glycogen Storage Disease ◽

Storage Disease ◽

Glycogen Storage Disease Type ◽

Glycogen Storage ◽

Vitamin D2 ◽

Mineral Density ◽

Dual Emission ◽

Cross Sectional ◽

Systemic Complications

IntroductionGlycogen storage disease III (GSD III) is an inborn error of carbohydrate metabolism that involves mainly the liver and skeletal muscles with rare potential systemic complications as osteoporosis. The aim of work of the current study was to screen children with GSD III for osteoporosis using Dual-emission-X-ray absorptiometry (DXA) scan and to measure associated parathormone (PTH) and vitamin D. Our secondary objective is to correlate between the degree of osteoporosis and the muscle state as well as the metabolic control.Material and methodsThis cross sectional study included 25 GSD III pediatric cases. The liver biochemical profile, creatine kinase (CK), vitamin D2, PTH levels were tested in addition to electromyogram (EMG), echocardiography and DXA. Twenty-five age and sex matched normal healthy controls were subjected to vitamin D2 analysis and compared to cases.ResultsThe mean ±SD age of the patients was 10.52 ± 3.1 years ranging between 5-18 years. Twenty-one patients (84%) had elevated CK levels, 14 patients (56%) had myopathy and three (12%) had sensory polyneuropathy and almost half of the patients had a mild degree of cardiac muscle hypertrophy. Ten patients (40%) had elevated PTH levels. Twenty-one patients (84%) and 96% of the controls had vitamin D2 deficiency. Thirteen patients (52%) had low BMD; two of them had osteoporosis. Patients with high CK levels significantly had low BMD (P= 0.04).ConclusionsPediatric GSD III patients have a significant prevalence of developing low BMD. It is strongly associated with myopathic changes but not significantly related to metabolic control.

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