## 4 Discussion  
GSD Ia is characterized by the deficiency of glucose-6-phosphatase activity. The main clinical manifestation is hypoglycemia, but patients also have high lactatemia, uric acid and triglyceride values. In addition, these patients have growth retardation and hepatomegaly [10]. The frequent intake of carbohydrates, to support blood glucose levels, provides a substrate for oral variogenic bacteria by implementing the risk of developing caries. Furthermore, the generalized growth retardation of these subjects could also explain the eruption delay of the dental elements [8; 9]. GSD Ib is a variant of GSD Ia; it is due to the defect of the glucose-6-phosphate transporter and presents further manifestations, such as neutropenia, altered neutrophil migration and bactericidal activity [16]. Patients are more susceptible to oral ulcers, periodontitis and oral cavity infections [16; 19]. Oral hygiene seems to be less effective in patients with GSD; [PERSON] et al. reported that toothbrushing may be overlooked at night, when the nasogastric tube is inserted for the overnight feeds, and in the morning, because the child needs a carbohydrate intake on waking once the nasogastric tube is removed [47]. In this way, dental prevention needs to be the basis for patients with GSD. Reinforced oral hygiene education, fluoride supplementation, and frequent dental appointments should be necessary to minimize the risk of oral issues and from increased cariogenic exposures [9]. In some reported articles, GSD I is associated with other systemic diseases. In particular, the work of [PERSON] et al. [13] found a strong association between GSD Ib and inflammatory bowel disease (IBD). The authors reported several intraoral manifestations that could be related to the IBD, in which the oral presentations are well documented, and therefore cannot be directly attributable to GSD. [PERSON] et al. [15] reported the presence of dry lips and \"beefy red appearance\" of the tongue and oral mucosa in a patient with GSD Ib suffering from nutritional deficiency. In this case, also, the oral manifestations could not be strictly related to the GSD, but rather to the lower serum iron, folate and vitamin B12 levels, caused by the special diet with several restrictions. GSD III is due to a deficiency of the enzyme amylo-1,6-glucosidase; in this pathology, the most common symptoms are hepatomegaly, hypoglycemia, recurrent diseases and infections. In addition, these patients are also affected by failure to thrive [48]. Muscle involvement, instead, is more present in GSD IIIa, a subtype of GSD III. According to [PERSON] et al. [40], the cranio-facial skeletal anomalies could derive from an incorrect cervico-lumbar posture due to hepatomegaly, together with oral respiration caused by reduced lung expansion. Muscular hypotrophy could also play a decisive role in dysmorphogenesis [41]. GSD II is caused by a deficiency of the acid alpha-1,4-glucosidase enzyme, which leads to an accumulation of glycogen in the muscle tissues. This glycogen storage causes muscle weakness and macroglossia, affecting the chewing and swallowing abilities of patients. Curiously, a single case report reported a massive gingival overgrowth. The authors, even if unable to fully explain the oral manifestation, hypothesized that a mixture of chronic inflammation, dryness of the gingiva, and the slight glycogen accumulation in the fibroblasts might have performed a role in the etiology of the patient's gingival overgrowth. The manifestations in patients with GSD V are comparable to those with GSD II. GSD V also affects the muscles and this is due to the deficiency of muscular phosphorylase [43]. Patients show a muscular intolerance syndrome to the effort, associated with myalgia, cramps, fatigue and muscle weakness. GSD XIV is caused by phosphoglucomutase-1 deficiency; manifestations such as cleft palate, bifid uvula and Pierre-Robin syndrome are characteristic of this pathology [45].