Type I Gaucher disease (GDI) in three siblings: enzyme replacement treatment (ERT) required (original) (raw)
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Type I Gaucher Disease in Children with and Without Enzyme Therapy
Pediatric Hematology and Oncology, 2002
This retrospective study describes the course of 56 children with non-neuronopathi c Gaucher disease who presented at <16 years and were followed at 6-to 12-month intervals for 3± 9 years. Massive splenomegal y and height retardation marked those who required treatment. Enzyme replacement signi® cantly increased hemoglobi n levels; platelet counts were divergent at presentation and follow-up, regardless of therapy. Among treated patients there was a signi® cant reduction in liver and spleen index volumes, and a signi® cant increase in height z-scores. None of the children required splenectomy or developed lung involvement. Many patients diagnosed due to large-scale screening were very mildly affected and remain untreated.
Clinical and diagnostic findings of 19 Gaucher patients in Albania
Aim: Gaucher disease is a multisystemic disorder characterized by glucocerebrosidase enzyme deficiency. The aim of this study was to present clinical aspects and diagnostic data of 19 patients (17 type 1, 2 type 3) in our service. Methods: Clinical findings, genetic analysis, laboratory work up, liver and spleen volumes were analyzed for 19 patients. Results: Mean age was 17 years (5-32 years); mean age at diagnosis was 11, 4 years (5-31 years). Most common presenting symptom was splenomegaly (all patients). Most frequent mutation was heterozygous N370S. One patient had severe anemia before the treatment. 16 patients had thrombocytopenia. All patients had high level of chitotriosidase before the treatment (240 times higher than normal value). Conclusion: There is a large variety of clinical signs in Gaucher disease. In our experience a proper investigation of patient followed by further expensive examinations is the cornerstone of diagnostic.
2021
We report on a case of a little girl patient diagnosed with Gaucher disease (GD) type 1 in her early childhood and our first experience with enzyme replacement therapy (ERT). She was first diagnosed accidentally with enlarged spleen during a pediatric examination when she was three years old, but the family ignored investigations; she was hospitalized for diagnosis at six years old. The GD was confirmed based on: clinical manifestations of left abdominal flank pain, multiple bruising, general weakness, bone pain, low appetite, failure to thrive <5th percentile, minor hepato- and severe splenomegaly, enlarged submaxillary lymph nodes, associated by anemia with normal platelets; low activity of beta-Glucosidase, two found mutations in GBA gene, Gaucher cells in bone marrow. The ERT was initiated with Imiglucerase (54 UI/kg/2 wks) two years later after diagnosis, avoiding the splenectomy. Subsequently, the platelets showed the first a promising result, gradually increasing their num...
Gaucher Disease Type I: A Case Report
Acta Medica Bulgarica, 2020
Gaucher disease (GD) is a multi-systemic disease with a low population frequency. It is a lysosomal storage disorder (LSD) that causes accumulation of glucocerebroside in the so called Gaucher cells predominantly in areas like the spleen, liver and bone marrow. Type I GD (GDI) is the most common form and usually does not involve the brain and the spinal cord. The symptoms can range from mild to severe and may appear anytime from childhood to adulthood. Diagnostics can often be challenging and imposes looking at person's medical history, symptoms, physical exam, and laboratory test results. We present a difficult to diagnose case of a 34-year-old woman admitted to the Clinic of Hematology, "Sv. I. Rilski" hospital with splenomegaly, normal laboratory findings and non-enlarged liver. She didn't show focal neurological symptoms. A series of tests were assigned including genetic targeted analysis. The case is an example of a rare genetic disease with mild clinical symptoms. Diagnosis of Gaucher disease, type I was confirmed by measurement of a GBA enzyme activity and identification of mutations in the GBA gene inherited in an autosomal recessive manner. Thanks to the efforts of the clinical team, the assignment of adequate clinical and laboratory tests and their correct interpretation, the patient was subjected to enzyme replacement therapy (ERT). Although the diagnosis was settled relatively late (at 34 years of age), the correct therapy slowed down the invalidation and improved the quality of life of the patient.
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.
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...
2008
Gaucher disease (GD) is an autosomal recessive inborn error of metabolism, resulting from a deficiency of the enzyme glucocerebrosidase, causing an accumulation of the glycolipid glucocerebroside within lysosomes of macrophages in the reticuloendothelial system. Three major clinical forms have been assigned and more than 200 gene mutations have been identified. We herein report a Lebanese boy born with a novel combined mutation L371V/Rec-NciI, who presented with moderate-severe type 1 GD. An overview of the clinical and biomarker improvement following enzyme replacement therapy with imiglucerase is described in a follow-up of 30 months. Imiglucerase seems to be efficacious in decreasing the severity of the disease associated with this mutation. However, a high dose may be required to achieve optimal growth, platelet count, and hemoglobin level.
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.
Orphanet Journal of Rare Diseases, 2017
Background: The enzymatic replacement therapy (ERT) availability for Gaucher disease (GD) has changed the landscape of the disease, several countries have screening programs. These actions have promoted the early diagnosis and avoided many complications in pediatric patients. In Spain ERT has been available since 1993 and 386 patients have been included in the Spanish Registry of Gaucher Disease (SpRGD). The aim of this study is to analyze the impact of ERT on the characteristics at time of diagnosis and initial complications in pediatric Gaucher disease patients. Aim: To analyze the impact of ERT on the characteristics at time of diagnosis and initial complications in pediatric Gaucher disease patients. Methods: A review of data in SpRGD from patients' diagnosed before 18 years old was performed. The cohort was split according the year of diagnosis (≤1994, cohort A; ≥1995, cohort B). Results: A total of 98 pediatric patients were included, GD1: 80, GD3: 18; mean age: 7.2 (0.17-16.5) years, 58 (59.2%) males and 40 (40.8%) females. Forty-five were diagnosed ≤ 1994 and 53 ≥ 1995. Genotype: N370S/N370S: 2 (2.0%), N370S/L444P: 27 (27.5%), N370S/other: 47 (48%), L444P/L444P: 7 (7.1%), L444P/D409H: 2 (2.0%), L444P/other: 3 (6.2%), other/other: 10 (10.2%). The mean age at diagnosis was earlier in patients diagnosed after 1995 (p < 0.001) and different between the subtypes, GD1: 8.2 (0.2-16.5) years and GD3: 2.8 (0.17-10.2) years (p < 0.001). There were more severe patients in the group diagnosed before 1994 (p = 0.045) carrying L444P (2), D409H (2), G377S (1), G195W (1) or the recombinant mutation. The patients' diagnosed ≤1994 showed worse cytopenias, higher chance of bone vascular complications at diagnosis and previous spleen removal. The patients started ERT at a median time after diagnosis of 5.2 years [cohort A] and 1.6 years [cohort B] (p < 0.001). Conclusions: The early diagnosis of Gaucher disease in the era of ERT availability has permitted to reduce the incidence of severe and irreversible initial complication in pediatric patients, and this has permitted better development of these patients. This is the largest pediatric cohort from a national registry.
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...