# Gaucher Disease in Internal Medicine and Dentistry
## 3 GD in Internal Medicine  
The GD clinical signs and symptoms are several and involve many organs and apparatus. The systemic manifestations should be divided into hematological, visceral, neurological, skeletal and metabolic. In this section, we describe the main findings of GD (Table 1). * _Hematopoietic system_ Among the apparatus and organs affected by GD, the hematopoietic system is widely involved. In this regard, the most common early signs are represented by the anemia and the thrombocytopenia. Another important sign is the splenomegaly, which comes from the suppression of hematopoiesis due to the deposits of GCs in bone marrow, which leads also to pancytopenia. In addition, monoclonal and polyclonal gammopathies are described. These manifestations expose the patient to a higher risk of developing myeloma. Therefore, the immune dysregulation may create a favorable environment for the solid cancer and hematological neoplasms onset [3]. Furthermore, in GD patients are described acquired and inherited alterations in the coagulation system, especially coagulation factors deficiencies. Dysfunctional platelet aggregation and low-grade disseminated intravascular coagulation (DIC) have been reported [4]. * _Liver_ Another organ commonly affected in GD is the liver, and hepatomegaly is one of the manifestations. The increase in the hepatic and biliary markers is often observed. The long-term hepatic complications of GD are fibrosis, cirrhosis and portal hypertension, which represent high-risk factors for hepatocarcinoma (HCC). The main processes at the base of the onset of HCC are various abnormalities, such as the alterations in iron metabolism, the insulin resistance, the immune dysregulation, the endoplasmic reticulum stress, the splenectomy, etc. [5]. * _Nervous system_ Individuals with type 2 or 3 GD are affected by severe neurological disorders. The pyramidal system involvement is often encountered. It appears with classic signs, such as opisthotonus, head retroflexion, spasticity and trismus. Moreover, bulbar signs, such as stridor, squint and swallowing difficulty, are also present. Other neurological manifestations, which can occur, are: the oculomotor apraxia, the saccadic initiation failure, the opticokinetic nystagmus, the generalized tonic-clonic seizures and the progressive myoclonic epilepsy [4]. Patients with heterozygous or homozygous GBA1 mutation are more at risk for developing an early Parkinson's disease. The GCase deficiency leads to the lack of \(\alpha\)-synuclein metabolism. Consequently, the accumulation of \(\alpha\)-synuclein results in neurotoxicity, especially in the substantia nigra. In addition, Glcer, namely, a GCase's substrate, stabilizes the oligomers of \(\alpha\)-synuclein, which in turn create aggregates, called Lewy bodies, in nervous cells [1]. * _Cardiovascular system_ Among the different GD types previously described, there is the cardiovascular form, in which a specific genotype (p.Asp448 His allele) corresponds to a rare phenotype with prevalent cardiovascular clinical manifestations, mainly calcification of the mitral and aortic valves [4]. * _Pulmonary apparatus_ Even if it is considered very rare, the pulmonary implication in GD is reported. The main patterns of lung damage identified are: the thickening of the interlobular and intralobular septa, the opacities in the alveoli and intercellular space and the blockage of capillaries. Furthermore, fibrosis of the pulmonary tissues and engagement of the hilar and mediastinal lymph nodes have been reported [6]. * _Metabolic pathways_ GD is also associated with metabolic issues. It has been stated that GD patients register an excessive energy expenditure, probably related to the macrophage activation and to the increased release of pro-inflammatory cytokines [5; 7]. It was also assumed that GD patients were more predisposed to register an increase in body weight and in fat mass, due to the enzymatic replacement treatment (ERT) [7]. On the contrary, a study conducted by [PERSON] et al.