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Gaucher disease. Unusual presentation and mini-review
Neurosciences (Riyadh, Saudi Arabia), 2015
We aim to describe an 8-year-old boy with an unusual clinical presentation of Gaucher disease (GD). Gaucher disease is a progressive lysosomal storage disorder due to deficiency of the specific enzyme glucocerebrosidase with varying clinical features, but often involving the monocytes-macrophages systems. This child ran a progressive course with a devastating outcome. Three distinct GD subtypes have been described with varying clinical features based on the presence or absence of neurologic involvement. Gaucher disease diagnosis is obtained via: enzyme activity assay, gene mutation study, bone marrow aspiration in addition to multiple other tests that have been successfully used in diagnosis of cases of GD. Treatment modalities include enzyme replacement treatment, substrate reduction therapy, bone marrow transplantation, blood transfusion, and surgery are available management modalities for GD. Gaucher disease is a chronic disease requiring a multidisciplinary team approach with re...
2024
Gaucher disease (GD) is a rare inherited lysosomal storage disorder resulting from mutations in the GBA gene, which encodes the enzyme glucocerebrosidase. This deficiency leads to the accumulation of glucosylceramide within macrophages, forming Gaucher cells and causing diverse clinical manifestations. The disease is classified into three types: Type 1 (non-neuronopathic), Type 2 (acute neuronopathic), and Type 3 (chronic neuronopathic), with Type 1 being the most common. The clinical presentation includes hepatosplenomegaly, anemia, thrombocytopenia, and bone pain, among others. Recent advancements in genetic understanding and therapeutic strategies, such as enzyme replacement therapy (ERT) and substrate reduction therapy (SRT), have improved clinical outcomes. This review focuses on the genetic basis, clinical features, diagnostic strategies, treatment options, and future research directions in Gaucher disease.
Proceedings of the National Academy of Sciences, 1990
Enzyme replacement has been under consideration as a therapeutic strategy for patients with Gaucher disease for more than two decades. Previous studies indicated that single injections of purified glucocerebrosidase reduced the amount of storage material in the liver. It was important to determine whether administration of exogenous enzyme on a regular basis would be of clinical benefit. We report here that weekly i.v. infusions of a macrophage-targeted preparation of human placental glucocerebrosidase in a child with type 1 Gaucher disease increased hemoglobin from 6.9 +/- 0.8 g/dl (+/- 1 SD) to 10.2 +/- 0.4 g/dl (+/- 1 SD) over a 20-week period. The platelet count also increased from a pretreatment value of 30,000 +/- 7000/mm3 (+/- 1 SD) to 54,000 +/- 11,000/mm3 (+/- 1 SD). Phagocytic activity in the spleen decreased during the period of enzyme administration, and there was radiographic evidence of skeletal improvement. These observations document objective clinical responses to e...
Clinical manifestations and management of Gaucher disease
Clinical Cases in Mineral and Bone Metabolism, 2015
Gaucher disease is a rare multi-systemic metabolic disorder caused by the inherited deficiency of the lysosomal enzyme β-glucocerebrosidase, which leads to the accumulation of its normal substrate, glucocerebroside, in tissue macrophages with damage to haematological, visceral and bone systems. Anaemia, thrombocytopenia, enlargement of liver and/or spleen, skeletal abnormalities (osteopenia, lytic lesions, pathological fractures, chronic bone pain, bone crisis, bone infarcts, osteonecrosis and skeletal deformities) are typical manifestations of the most prevalent form of the disease, the so-called non-neuronopathic type 1. However, severity and coexistence of different symptoms are highly variable. The determination of deficient βglucocerebrosidase activity in leukocytes or fibroblasts by enzymatic assay is the gold standard for the diagnosis of Gaucher disease. Comprehensive and reproducible evaluation and monitoring of all clinically relevant aspects are fundamental for the effective management of Gaucher disease patients. Enzyme replacement therapy has been shown to be effective in reducing glucocerebroside storage burden and diminishing the deleterious effects caused by its accumulation. Tailored treatment plan for each patient should be directed to symptom relief, general improvement of quality of life, and prevention of irreversible damage.
Gaucher’s Disease in a 2 Years Old Child: A Case Report
American Journal of Pediatrics, 2020
Gaucher's Disease (GD) is an autosomal recessive systemic lysosomal storage disorder, characterized by glucocerebroside deposition in cells of macrophage-monocyte system as result of deficiency in lysosomal β-glycosidase (glucocerebrosidase). GD is a rare genetic disorder. It is the most common among the lysosomal storage disorders. Hereby we report a 2-year-old male presented with weakness, pallor and gradually enlarge belly. In the beginning the diagnosis was suspected acute leukemia, an abnormality in hematooncology due to bisitopenia and organomegaly. Therefore patient was gone through Bone Marrow Aspiration (BMA) to confirm the diagnosis, however the results of 3 times BMA were not align with acute leukemia. Moreover the history and clinical examination pointed to be a lipid storage disease. Finally patient was diagnosed as GD after the smear of BMA showed foam cell. In addition the confirmation of Gaucher's disease was performed by measurement of glucocerebrosidase level, which resulted low in β-Glukosidase 0.97 uM/hr (normal level > 1.8 uM/hr). Therefore we emphasize the importance of early recognition by clinical manifestation and histological findings. GD should be considered as differential diagnosis of children with unexplained hepatosplenomegaly. Patients suspected with acute leukemia should be examined for possibility of GD from bone marrow smear. Furthermore, early recognition of GD would lead to safe and effective treatment with enzyme replacement which can decrease morbidity.
Diagnosis of Lysosomal Storage Disorders: Gaucher Disease
Current Protocols in Human Genetics, 2001
Gaucher Disease (GD) is a progressive lysosomal storage disorder caused by deficiency of glucocerebrosidase (GBA). The clinical phenotype follows a spectrum ranging from severe early-onset to milder late-onset disease. The absence of neurological involvement defines GD type I, whereas neuronopathic features define GD type II and III. Early diagnosis may be important for timely initiation of enzyme replacement therapy to prevent disease complications, although the enzyme does not cross the blood brain barrier. Diagnosis of GD can be readily achieved by analysis of GBA in leukocytes, fibroblasts, and/or dried blood spots using fluorometric, microfluidic or mass spectrometry-based assays. Low GBA activities are typically confirmed through molecular analysis of the GBA gene. GBA analysis in dried blood spots may be attractive for high-throughput screening of at-risk individuals and/or newborn infants. The method detailed in this unit is based on GBA analysis by tandem mass spectrometry following incubation of dried blood spots with the GBA-specific substrate D-glucosyl-β1-1-N-dodecanoyl-D-erythrosphingosine [C12-glucocerebroside (C 36 H 69 NO 8)] and internal standard N-myristoyl-Derythro-sphingosine [C14-ceramide (C 32 H 63 NO 3)]. GBA activities in more than 2,000 newborn infants showed a mean of 22.0 ± 13.8 μmol/hr/liter (median: 19.9 μmol/hr/liter; 95% CI: 21.41-22.59 μmol/hr/liter). GBA activities in an adult population (n >1,200) showed generally lower enzyme activities than newborns, with a mean of 9.87 ± 9.35 μmol/hr/liter (median: 8.06 μmol/hr/liter). GBA activities in ten adult patients with confirmed GD were less than 4.2 μmol/hr/liter and in seven infants and children with GD less than 1.24 μmol/hr/liter. This method is robust, sensitive, and suitable for high-throughput analysis of hundreds of samples.
Gaucher disease and its treatment options
The Annals of pharmacotherapy, 2013
To review the epidemiology, pathophysiology, and treatments of Gaucher disease (GD), focusing on the role of enzyme replacement therapy (ERT), andsubstrate reduction therapy (SRT). A literature search through PubMed (1984-May 2013) of English language articles was performed with terms: Gaucher's disease, lysosomal storage disease. Secondary and tertiary references were obtained by reviewing related articles. All articles in English identified from the data sources, clinical studies using ERT, SRT and articles containing other interesting aspects were included. GD is the most common inherited LSD, characterized by a deficiency in the activity of the enzyme acid β-glucosidase, which leads to accumulation of glucocerebroside within lysosomes of macrophages, leading to hepatosplenomegaly, bone marrow suppression, and bone lesions. GD is classified into 3 types: type 1 GD (GD1) is chronic and non-neuronopathic, accounting for 95% of GDs, and types 2 and 3 (GD2, GD3) cause nerve cell ...
A Review of Gaucher Disease Pathophysiology, Clinical Presentation and Treatments
International journal of molecular sciences, 2017
Gaucher disease (GD, ORPHA355) is a rare, autosomal recessive genetic disorder. It is caused by a deficiency of the lysosomal enzyme, glucocerebrosidase, which leads to an accumulation of its substrate, glucosylceramide, in macrophages. In the general population, its incidence is approximately 1/40,000 to 1/60,000 births, rising to 1/800 in Ashkenazi Jews. The main cause of the cytopenia, splenomegaly, hepatomegaly, and bone lesions associated with the disease is considered to be the infiltration of the bone marrow, spleen, and liver by Gaucher cells. Type-1 Gaucher disease, which affects the majority of patients (90% in Europe and USA, but less in other regions), is characterized by effects on the viscera, whereas types 2 and 3 are also associated with neurological impairment, either severe in type 2 or variable in type 3. A diagnosis of GD can be confirmed by demonstrating the deficiency of acid glucocerebrosidase activity in leukocytes. Mutations in the GBA1 gene should be identi...
The Journal of Pediatrics, 2004
ype 1 Gaucher disease is the most common lysosomal storage disease and the most common genetic disorder among persons of Ashkenazi Jewish descent. It is caused by deficiency of the enzyme glucocerebrosidase, which is necessary for the intralysosomal catabolism of glucocerebroside (GC), and is inherited in an autosomal recessive fashion. 1,2 This results in accumulation of GC (most of which is derived from phagocytosed cell membranes) in the lysosomes of monocyte-derived macrophages in tissues of the reticuloendothelial system. 3,4 Accumulation in the Kupffer cells of the liver and in splenic macrophages is associated with enlargement of these organs. The resulting hypersplenism produces progressive anemia and thrombocytopenia. Accumulation of GC in bone marrow is associated with osteopenia, lytic lesions, pathologic fractures, chronic bone pain, acute episodes of excruciating ''bone crisis,'' bone infarcts, and osteonecrosis. Although anemia and thrombocytopenia may be severe, it is usually bone disease that results in the greatest morbidity and long-term disability. Type 1 Gaucher disease responds well to enzyme replacement therapy (ERT) with recombinant human macrophage-targeted recombinant human glucocerebrosidase (imiglucerase, Cerezyme, Genzyme Corporation, Cambridge, Mass). 5-7 Treatment results in breakdown of stored GC, reduction in liver and spleen size, amelioration or resolution of anemia and thrombocytopenia, decreased bone pain, and increased bone mineralization and remodeling over a period of several years. 7-9 Although type 1 Gaucher disease is often referred to as the ''adult type,'' the age of onset and rate of progression vary widely, and more than half of all patients are diagnosed before the age of 10 years. Among those diagnosed before age 10, 68% are diagnosed even before age five. 10 When children with type 1 Gaucher disease exhibit symptoms, the disease is more severe, requiring more frequent monitoring and early intervention. In addition to the effects of the disease described previously, children with type 1 Gaucher disease are frequently growth-restricted and have delayed onset of puberty; 50% of symptomatic children are at or below the third percentile for height, and another 25% are shorter than expected based on their midparental height. 11 The organomegaly is particularly noticeable in young children, who often have markedly protuberant abdomens. Chronic pain and fatigue may affect school performance and participation in physical activities. That children with type 1 Gaucher disease are different than adults with this disorder is also evident from the genotypes observed (Table I). Homozygosity for the N370S mutation, commonly found in mildly affected adults, is much less common in symptomatic children. In contrast, genotypes including the 84GG or L444P alleles, typically associated with more severe disease, are more common in patients who exhibit signs of Gaucher disease during childhood, than in patients who first exhibit symptoms later in life.
Gaucher Disease in a 15-month-Old Child: A Case Report and Literature Review
2022
Gaucher Disease (GD) is an autosomal recessive systemic lysosomal storage disorder, characterized by glucocerebroside deposition in cells of macrophage-monocyte system and accumulation of glucosylceramide in different organs as result of deficiency in lysosomal β-glycosidase (glucocerebrosidase). Accumulation of glucosylceramide in tissues leads to multisystem organ involvement including liver, spleen, bone marrow, lungs and central nervous system. GD is a rare genetic disorder. It is the most common among the lysosomal storage disorders. Around 5 cases are identified and diagnosed in UAE in 2013. Early recognition of GD is crucial as there is effective treatment with enzyme replacement which can decrease morbidity. GD should be considered as differential diagnosis of children with unexplained hepatosplenomegaly. Hereby, we report a case of Gaucher disease in a 15-monthold child, in whom a diagnosis of Gaucher disease was made early based on glucocerebrosidase levels estimation.