Abstract in English:

Abstract Gaucher disease type 1 (GD1) is the most common lysosomal storage disorder, characterized by hepatomegaly, splenomegaly, anemia, thrombocytopenia, and skeletal manifestations, which significantly affect quality of life. This systematic review aimed to assess the current state of the disease, focusing on skeletal manifestations. A systematic search was conducted between 2000 and February 2024 in multiple languages using PRISMA-ScR and JBI methods. A total of 96 studies were identified: 23 systematic reviews, 23 descriptive studies, 17 case reports, 13 experimental studies, 10 retrospective studies, 4 observational studies, 4 prospective studies, and 2 cross-sectional studies. The highest number of articles on the topic was published in 2015, and the countries with the most publications were the USA, Italy, Brazil, and Argentina over the 23 years covered in the search. These studies cover various aspects of GD1, including skeletal features, patient phenotypes, clinical annotations, diagnostics, therapies, and patient perspectives. Despite advances, challenges such as disease heterogeneity and inconsistent results persist. This review underscores the importance of further research to improve understanding and management of GD1, with an emphasis on skeletal manifestations.

Abstract in English:

Abstract 3-hydroxyisobutyryl-CoA hydrolase deficiency (HIBCHD) is a rare metabolic disease. Early symptoms include poor feeding, seizures, hypotonia and impaired psychomotor development. Acute metabolic crisis can cause encephalopathy with high risk of neurological sequelae or death. Casuistic, we here report a nine-year old Danish girl with HIBCHD treated with intravenous high-dose methylprednisolone when presenting with encephalopathy during acute metabolic crisis. Presentation of acute encephalopathy with basal ganglia changes seen on MRI was regarded as acute disseminated encephalomyelitis (ADEM) leading to intravenous high-dose methylprednisolone treatment. The effect of methylprednisolone was profound, not only on the acute neurological symptoms, but also accelerated the development of the child. After re-evaluation of MR images, Whole Genome Sequencing (WGS) confirmed the diagnosis HIBCHD. The high-dose methylprednisolone treatment regime was repeated in a following severe metabolic crisis presenting with acute encephalopathy, dystonia and spasticity. The child survived and after rehabilitation neurological sequelae are present but considerably reduced. We consider if high-dose methylprednisolone should be recommended in children with acute metabolic crisis and encephalopathy due to HIBCHD. Since influenza A virus was the triggering cause to metabolic crisis with encephalopathy, vaccination should be considered in HIBCHD.

Abstract in English:

Abstract Fabry disease (FD) is an X-linked inborn error of glycosphingolipid metabolism characterized by progressive lysosomal deposition of partially metabolized substrates within various tissues. This condition results in significant morbidity and mortality for both men and women. However, the severity and progression of the disease differ by sex due to potential factors that modulate the phenotype in women, such as X chromosome inactivation. In this study, we conducted methylation assays on peripheral blood samples from seven women diagnosed with FD and examined the correlation between these assays and the clinical severity of the disease. The results showed no correlation, underscoring the importance of selecting appropriate tissues for analysis.

Abstract in English:

Abstract Niemann-Pick disease type C (NPC) disease is a lysosomal storage disorder caused by alterations in the trafficking of unesterified cholesterol due to mutations in the NPC1 and NPC2 genes. Its manifestations can be visceral, neurological, and psychiatric. This study conducts a retrospective review to assess the clinical, laboratory, molecular, and imaging features of a cohort of Brazilian patients with NPC. Eleven cases were included, 6 females and 5 males, aged between 3 and 32 years. Three cases corresponded to the early infantile form, three to the late infantile form, four to the juvenile, and one to the adult form. The most frequent symptoms were splenomegaly (10/11), hepatomegaly (8/11), vertical supranuclear gaze palsy (11/11), ataxia (10/11), dysarthria (10/11), dysphagia (10/11), spasticity (7/11), epilepsy (7/11), dystonia (7/11), cognitive impairment (8/11), and school delay (8/11). All patients exhibited non-specific abnormalities in brain imaging studies. Biomarker-specific tests were positive in 9 out of 11 cases. The Filipin test was "classic" in 6 cases and "variant" in 5. Mutations in NPC1 were identified in all patients, with the most prevalent variant being p.Ala1035Val (8/11). This case series highlights the p.Ala1035Val mutation in NPC1 correlates with the "classic" profile of Filipin staining.