Gaucher's Disease - A case report

Gaucher's Disease (GD) is an autosomal recessive systemic lysosomal storage disorder which is characterized by glucocerebroside deposition in cells of the macrophage-monocyte system as a result of a deficiency in lysosomal P-glycosidase (glucocerebrosidase). GD is a rare genetic disorder. It is the most common amongst the lysosomal storage disorders. GD has been categorised into three types based on the presence of central nervous involvement1. Type 1 is a non-neuronopathic form that presents in childhood or early adulthood. Type 2 is acute neuronopathic form that presents in childhood. It progresses rapidly and is fatal. Type 3 is chronic non-neuronopathic form that presents in childhood but is slowly progressive. Here we describe a case of a three and a half year old male child in whom a diagnosis of Gaucher's disease was made based on bone marrow biopsy and later confirmed by glucocerebrosidase levels estimation.

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Gaucher’s disease

Batna Journal of Medical Sciences (BJMS) ◽

10.48087/bjmstf.2015.2115 ◽

2015 ◽

Vol 2 (1) ◽

pp. 66-69

Author(s):

Fadia Rahal ◽

◽

Nadjia Brahimi ◽

Aicha Ladjouze-Rezig

Keyword(s):

Qualité De Vie ◽

Gaucher's Disease ◽

Gaucher’S Disease ◽

Type 3

La maladie de Gaucher (MG) est une maladie lysosomale due au déficit génétique en bglucosidase, de transmission autosomique récessive ; on en distingue trois types. La MG de type 1, la plus fréquente, se caractérise par une splénomégalie dans 90% des cas, une cytopénie (essentiellement, anémie et thrombopénie), et une atteinte ostéoarticulaire infiltrative et destructrice qui impacte souvent la qualité de vie des patients. Les deux autres phénotypes incluent une atteinte neurologique, sévère dans le type 2 qui affecte le nourrisson et évolue rapidement vers le décès, et plus lentement progressive dans le type 3 qui comporte également les symptômes du type 1. Le diagnostic repose sur le dosage de la bglucosidase dans les leucocytes. Cependant, la maladie de Gaucher reste peu connue, et son diagnostic est souvent fait tardivement particulièrement en milieu rhumatologique ou se sont essentiellement les différentes complications ostéarticulaires associées aux manifestations hématologiques qui permettent d’orienter vers cette maladie. Par ailleurs, l’approche thérapeutique dominante est l’enzymothérapie substitutive (ETS), disponible actuellement pour certaines maladies lysosomales.

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Clinical Features of Infantile GM1 Gangliosidosis: Report of an Iranian Patient

World Journal of Peri & Neonatology ◽

10.18502/wjpn.v3i1.5066 ◽

2020 ◽

Author(s):

Mahtab Ordooei ◽

Razieh Fallah ◽

Fatemeh Abdi ◽

Fahimeh Soheilipour

Keyword(s):

Lysosomal Storage ◽

Gm1 Gangliosidosis ◽

Case Presentation ◽

Iranian Patient ◽

Cherry Red Spot ◽

Type 3 ◽

Initial Check ◽

Infantile Type

Background: GM1 gangliosidosis is an autosomal recessive lysosomal storage disease due to a lack of β-galactosidase activity, exactly because of mutations in the GLB1 gene. GM1 gangliosidosis is a rare disease that could occur either during infancy (infantile type 1), as a juvenile (type 2), or in adulthood (type 3) in both nervous and skeletal systems. Type 1 is characterized by premature psychomotor deterioration, visceromegaly, macular cherry-red spot, skeletal deformities, and death in the first 2 years of life. Case Presentation: We reported an Iranian infant who, on initial check-up, had coarse face, visceromegaly, dystonia, and hepatosplenomegaly that increased at 15 months of age. At the initial check-up, a genetic test was performed and GM1 gangliosidosis type 1 was diagnosed. Conclusion: infant form is characterized by early-onset before the age of 6 months and rapidly progressive psychomotor deterioration, facial abnormalities, and visceromegaly.

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Sucrose gradient analysis of phospholipid-activated β-glucosidase in type 1 and type 2 Gaucher's disease

Archives of Biochemistry and Biophysics ◽

10.1016/0003-9861(85)90173-0 ◽

1985 ◽

Vol 238 (1) ◽

pp. 344-352 ◽

Cited By ~ 11

Author(s):

Kevin O. Garrett ◽

Elizabeth M. Prence ◽

Robert H. Glew

Keyword(s):

Sucrose Gradient ◽

Gradient Analysis ◽

Gaucher's Disease ◽

Gaucher’S Disease

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Gaucher’s Disease in Lithuania: Its Diagnosis and Treatment

Medicina ◽

10.3390/medicina47070058 ◽

2011 ◽

Vol 47 (7) ◽

pp. 405

Author(s):

Gražina Kleinotienė ◽

Anna Tylki-Szymanska ◽

Barbara Czartoryska

Keyword(s):

Clinical Picture ◽

Hematological Parameters ◽

Bone Lesions ◽

Lysosomal Storage ◽

Gaucher's Disease ◽

Gaucher’S Disease ◽

Lysosomal Disease ◽

Therapeutic Goals ◽

Enzyme Replacement

Gaucher’s disease is a lysosomal storage disease caused by the lack of beta-glucocerebrosidase enzyme, leading to the accumulation of glucocerebroside. Gaucher’s disease is the most frequent type of sphingolipidosis as well as the most frequent lysosomal disease. Clinically, two forms of Gaucher’s disease are defined: nonneuronopathic form, so-called type 1, characterized by hepatosplenomegaly, thrombocytopenia, anemia, and osteopenia, and neuronopathic form, known as types 2 and 3, which are also characterized by hepatosplenomegaly, hematological and bone changes; however, involvement of the central nervous system dominates in the clinical picture. Severe deficiency of beta-glucocerebrosidase activity allows confirming the diagnosis based on the clinical picture or the findings of bone marrow examination. Treatment with human glucocerebrosidase was introduced in 1991. Clinically good results are achieved: not only accumulation of glucocerebroside is stopped, but also positive changes in the reticuloendothelial system and an improvement in development and hematological parameters of children are observed as well as the development of bone lesions is reduced. To date, Gaucher’s disease has been diagnosed in 8 patients in Lithuania: 3 persons have type 3 and 5 have type 1 disease. Enzyme replacement therapy was started in 2001, and currently 6 persons are being treated. In majority of patients, Gaucher’s disease was suspected after exclusion of other possible proliferative diseases. All patients within the first or second year of treatment achieved the therapeutic goals, namely: normalization of hematological parameters, reduction in liver and spleen volumes, and bone pain relief.

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Enzyme replacement treatment in type 1 and type 3 Gaucher's disease

The Lancet ◽

10.1016/s0140-6736(94)90462-6 ◽

1994 ◽

Vol 344 (8938) ◽

pp. 1679-1682 ◽

Cited By ~ 44

Author(s):

B Bembi ◽

E Agosti ◽

M Zanatta ◽

M Carrozzi ◽

R Gornati ◽

...

Keyword(s):

Gaucher's Disease ◽

Gaucher’S Disease ◽

Enzyme Replacement ◽

Replacement Treatment ◽

Type 3

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Gaucher disease: clinical phenotypes and refining GBA mutational spectrum in Thai patients

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-021-02151-2 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Tim Phetthong ◽

Thipwimol Tim-Aroon ◽

Arthaporn Khongkraparn ◽

Saisuda Noojarern ◽

Chulaluck Kuptanon ◽

...

Keyword(s):

Gaucher Disease ◽

Age Of Onset ◽

Lysosomal Storage ◽

Pathogenic Variants ◽

Medical Centers ◽

Neurologic Involvement ◽

Therapeutic Research ◽

Type 3

Abstract Background Gaucher disease (GD) is a rare lysosomal storage disorder, characterized by hepatosplenomegaly and pancytopenia, with or without neurologic involvement. The disorder is categorized into three phenotypes: GD type 1 or nonneuronopathic GD; GD type 2 or acute neuronopathic GD; and GD type 3 or chronic neuronopathic GD. The purposes of this study were to describe clinical characteristics of Thai GD in patients diagnosed and/or followed up during 2010–2018 and to perform re-genotyping including analysis of GBA recombinant alleles which had not been investigated in Thai patients before. Results There were 27 patients from seven medical centers, enrolled in the study. All the cases had pediatric onset. GD3 (44.5%) was the most common phenotype, followed by GD2 (40.7%) and GD1 (14.8%), with one case of neonatal GD. The median age of onset for GD1, GD2, and GD3 was 72, 4 and 12 months, respectively, suggesting relatively earlier onset of GD1 and GD3 in Thai patients. All patients with GD1 and most patients with GD3 received ERT. Four patients with GD3 had ERT followed by HSCT. Patients with GD3 who received no or late ERT showed unfavorable outcomes. We identified 14 variants including two novel (p.S384F and p.W533*) and 12 reported pathogenic variants: p.L483P, p.N409S, p.R159W, p.P305A, p.A175G, p.D448H, p.V414L, IVS2+1G>A, IVS6-1G>C, IVS7+1G>C, IVS9-3C>G, and Rec1a. The p.L483P was the most prevalent allele found in this study, at 66% (33/50 alleles), followed by IVS2+1G>A, Rec1a, and IVS6-1G>C. Twenty-four percent of patients were reassigned with validated genotypes, most of whom (4 of 6) were patients with GD2. The [p.S384F + p.W533*] being compounded with p.L483P, was found in the patient with neonatal GD, suggesting that the p.S384F could potentiate the deleterious effect of the p.W533*, and/or vice versa. Conclusions Neuronopathic GD was strikingly prevalent among Thai affected population. Homozygous p.L483P was the most common genotype identified in Thai patients. Recombinant allele Rec1a and splicing mutations were associated with GD2 and severe cases of GD3. Mutation spectrum could be useful for designing stepwise molecular analysis, genetic screenings in population, and new therapeutic research for neuronopathic GD.

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Usher Syndrome

Audiology Research ◽

10.3390/audiolres12010005 ◽

2022 ◽

Vol 12 (1) ◽

pp. 42-66

Author(s):

Alessandro Castiglione ◽

Claes Möller

Keyword(s):

Autosomal Recessive ◽

Usher Syndrome ◽

Genetic Condition ◽

Review Reports ◽

New Treatments ◽

Loss Of Hearing ◽

Type 3 ◽

Autosomal Recessive Pattern

Usher syndrome (USH) is the most common genetic condition responsible for combined loss of hearing and vision. Balance disorders and bilateral vestibular areflexia are also observed in some cases. The syndrome was first described by Albrecht von Graefe in 1858, but later named by Charles Usher, who presented a large number of cases with hearing loss and retinopathy in 1914. USH has been grouped into three main clinical types: 1, 2, and 3, which are caused by mutations in different genes and are further divided into different subtypes. To date, nine causative genes have been identified and confirmed as responsible for the syndrome when mutated: MYO7A, USH1C, CDH23, PCDH15, and USH1G (SANS) for Usher type 1; USH2A, ADGRV1, and WHRN for Usher type 2; CLRN1 for Usher type 3. USH is inherited in an autosomal recessive pattern. Digenic, bi-allelic, and polygenic forms have also been reported, in addition to dominant or nonsyndromic forms of genetic mutations. This narrative review reports the causative forms, diagnosis, prognosis, epidemiology, rehabilitation, research, and new treatments of USH.

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Gaucher Disease: Case Report

Journal of Bioscience & Biomedical Engineering ◽

10.47485/2693-2504.1033 ◽

2021 ◽

Keyword(s):

Gaucher Disease ◽

Autosomal Recessive ◽

Genetic Disorder ◽

Autosomal Recessive Inheritance ◽

Lysosomal Storage ◽

Enzyme Replacement ◽

Disease Case ◽

Gaucher Disease Type 1 ◽

The Common

Gaucher disease is the most common lysosomal storage disease. It is marked by deficient glucocerebrosidase enzyme activity, leading to elective accumulation of its substrate in the lysosomes of macrophages. Macrophages are most often deposited in the liver, spleen and bone marrow, creating typical symptomatology in these organs. It is a genetic disorder with autosomal recessive inheritance pattern. The extent of the damage and severity of the symptoms increase in proportion to the genetic damage in the culprit gene, GBA1. As a result, the symptoms and course of the disease may range from mild to quite acute, with potential death of the patient at a young age. Case: Patient, 29, was diagnosed with Gaucher disease type 1 and underwent enzyme replacement therapy, with satisfactory response. Along with the common symptoms of the disease, he had also developed the rare Erlenmeyer flask deformity.

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Gaucher disease: clinical phenotypes and refining GBA mutational spectrum in Thai patients

10.21203/rs.3.rs-796169/v1 ◽

2021 ◽

Author(s):

Tim Phetthong ◽

Thipwimol Tim-Aroon ◽

Arthaporn Khongkraparn ◽

Saisuda Noojarern ◽

Chulaluck Kuptanon ◽

...

Keyword(s):

Gaucher Disease ◽

Age Of Onset ◽

Lysosomal Storage ◽

Pathogenic Variants ◽

Medical Centers ◽

Neurologic Involvement ◽

Therapeutic Research ◽

Type 3

Abstract Background Gaucher disease (GD is a rare lysosomal storage disorder, characterized by hepatosplenomegaly and pancytopenia, with or without neurologic involvement. The disorder is categorized into three phenotypes: GD type 1 or nonneuronopathic GD; GD type 2 or acute neuronopathic GD; and GD type 3 or chronic neuronopathic GD. The purposes of this study were to describe clinical characteristics of Thai GD in patients diagnosed and/or followed up during 2010–2018 and to perform re-genotyping including analysis of GBA recombinant alleles which had not been investigated in Thai patients before. Results There were 27 patients from seven medical centers, enrolled in the study. All the cases had pediatric onset. GD3 (44.5%) was the most common phenotype, followed by GD2 (40.7%) and GD1 (14.8%), with one case of neonatal GD. The median age of onset for GD1, GD2, and GD3 was 72, 4 and 12 months, respectively, suggesting relatively earlier onset of GD1 and GD3 in Thai patients. All patients with GD1 and most patients with GD3 received ERT. Four patients with GD3 had ERT followed by HSCT. Patients with GD3 who received no or late ERT showed unfavorable outcomes. We identified 14 mutations including two novel (p.S384F and p.W533*) and 12 reported pathogenic variants: p.L483P, p.N409S, p.R159W, p.P305A, p.A175G, p.D448H, p.V414L, IVS2 + 1G > A, IVS6-1G > C, IVS7 + 1G > C, IVS9-3C > G, and Rec1a. The p.L483P was the most prevalent allele found in this study, at 66% (33/50 alleles), followed by IVS2 + 1G > A, Rec1a, and IVS6-1G > C. Twenty-four percent of patients were reassigned with validated genotypes, most of whom (4 of 6) were patients with GD2. The [p.S384F + p.W533*] being compounded with p.L483P, was found in the patient with neonatal GD, suggesting that the p.S384F could potentiate the deleterious effect of the p.W533*, and/or vice versa. Conclusions Neuronopathic GD was strikingly prevalent among Thai affected population. Homozygous p.L483P was the most common genotype identified in Thai patients. Recombinant allele Rec1a and splicing mutations were associated with GD2 and severe cases of GD3. Mutation spectrum could be useful for designing stepwise molecular analysis, genetic screenings in population, and new therapeutic research for neuronopathic GD.

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