Case Report: A Novel LAMP2 Splice-Altering Mutation Causes Cardiac-Only Danon Disease

Danon disease (DD) is a rare glycogen storage lysosomal disorder caused by mutations in the LAMP2 gene. Patients with DD are usually characterized clinically by severe multisystem syndromes. We describe a specific family with a novel pathogenic splice-altering mutation in the LAMP2 gene (c.741+2T>C) with cardiac-only symptoms (frequent ventricular tachycardia, intraventricular block, and hypertrophic cardiomyopathy). Minigene assays were used to evaluate the consequence of the splice-site mutation in the LAMP2 gene. The results showed that the c.741+2T>C mutation led to extra 6-bp preservation of intron 5 at the junction between exons 5 and 6 during transcriptional processing of the mRNA, which creates a stop codon and truncated the LAMP2 protein to 248-amino-acid residues. The mutant LAMP2 protein was predicted to have a conformational change, lacks the important transmembrane domain, and subsequent protein destabilization.

Oral Findings of Children, Adolescents and Young Adults Affected by Muccopolysaccharidosis

Objectives: Mucopolysaccharidosis (MPS) comprises of a set of rare inherited lysosomal disorder which results in deposition of glycosaminoglycans (GAGs) in various tissues and organs resulting in disturbances in the developing structures. The aim of the study was to systematically record the oral findings of patients diagnosed with MPS and subsequently assess their oral health needs. Methodology: A cross- sectional study was conducted on patients diagnosed with MPS (n=57). Complete soft tissue and hard tissue examination was done and the findings recorded. DMFT or def indices were recorded in accordance with WHO criteria and methods. Results: The study showed that the patients diagnosed with MPS have higher oral health care needs owing to the anatomical and pathological changes. The study showed that the patients diagnosed with MPS had poor oral hygiene and high caries incidence. However, the number of filled teeth in spite of high caries index wassignificantly less which showed neglected oral care. Interpretation and Conclusion: The patients diagnosed with MPS have higher oral health care needs. Hence, regular dental evaluation and treatment must be incorporated in their health care regimen.

Splenic Artery Aneurysms, A Rare Complication of Type 1 Gaucher Disease: Report of Five Cases

Type 1 Gaucher disease is a rare genetic lysosomal disorder due to acid betaglucosidase deficiency. The main features are thrombocytopenia, anemia, hepatosplenomegaly and complex skeletal disease. Complications include pulmonary hypertension, cirrhosis and splenic infarction; comorbidities, such as autoimmune phenomena, B-cell malignancies and Parkinson disease also occur. Visceral aneurysms have been only rarely noted in Gaucher disease. We report the retrospective data from patients with Gaucher disease type 1 and splenic arterial aneurysm. We describe the different outcomes of a giant splenic arterial aneurysm in five patients with type 1 Gaucher disease and discuss the main possible pathophysiological explanations. Aneurysms of the splenic artery are rare in Gaucher disease but are probably greatly under-reported.

Gaucher disease: masquerading as chronic malaria

Gaucher disorder s rare lysosomal disorder characterized by glycolipid laden lysosomes leading to hepatosplenomegaly, bone marrow involvement. Three types of Gaucher disease have been described based on the clinical features, ethnicity and the natural history of the disease. Gaucher disease Type 1 (GD1) occurs mainly in infancy to adulthood and is the commonest lysosomal storage disorder. Gaucher Disease Type II (GD2) and Gaucher disease type III (GD3) patients have onset at less than 1 year, and 2-20 years, respectively.1 GD1 patients do not have neurological involvement. GD2 is the acute neuronopathic and GD3 is the chronic neuronopathic type.

Glucocerebrosidase and Parkinson Disease: Molecular, Clinical, and Therapeutic Implications

Parkinson disease (PD) is a complex neurodegenerative disease characterised by multiple motor and non-motor symptoms. In the last 20 years, more than 20 genes have been identified as causes of parkinsonism. Following the observation of higher risk of PD in patients affected by Gaucher disease, a lysosomal disorder caused by mutations in the glucocerebrosidase (GBA) gene, it was discovered that mutations in this gene constitute the single largest risk factor for development of idiopathic PD. Patients with PD and GBA mutations are clinically indistinguishable from patients with idiopathic PD, although some characteristics emerge depending on the specific mutation, such as slightly earlier onset. The molecular mechanisms which lead to this increased PD risk in GBA mutation carriers are multiple and not yet fully elucidated, they include alpha-synuclein aggregation, lysosomal-autophagy dysfunction and endoplasmic reticulum stress. Moreover, dysfunction of glucocerebrosidase has also been demonstrated in non-GBA PD, suggesting its interaction with other pathogenic mechanisms. Therefore, GBA enzyme function represents an interesting pharmacological target for PD. Cell and animal models suggest that increasing GBA enzyme activity can reduce alpha-synuclein levels. Clinical trials of ambroxol, a glucocerebrosidase chaperone, are currently ongoing in PD and PD dementia, as is a trial of substrate reduction therapy. The aim of this review is to summarise the main features of GBA-PD and discuss the implications of glucocerebrosidase modulation on PD pathogenesis.