Gaucher Disease Type I: A Case Report

AbstractGaucher 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.

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From Symptoms and Signs to Diagnosis in a Rare Disease, Type I Gaucher Disease

Internal Medicine ◽

10.2478/inmed-2018-0008 ◽

2018 ◽

Vol 15 (1) ◽

pp. 69-76

Author(s):

Mihaela Ghinea ◽

Sabina Ciocodei ◽

Gabriela Butoi ◽

Geandan Memet ◽

Andreea Stoica ◽

...

Keyword(s):

Laboratory Testing ◽

Gaucher Disease ◽

Storage Disease ◽

Disease Type ◽

Genetic Mutations ◽

Type I ◽

Lysosomal Storage ◽

Specific Enzyme ◽

Enzyme Replacement ◽

Symptoms And Signs

AbstractGaucher disease is the most frequent lysosomal storage disease, caused by the deficiency of an enzyme called β-glucocerebrosidase. Three types of Gaucher disease are described. Type I Gaucher disease benefits from lifelong enzyme replacement therapy with imiglucerase.Herein, we present the case of a 34-year-old female patient, a commercial worker, who was admitted to our Department of Haematology in the Emergency Clinical Hospital of Constanta in order to investigate the aetiology of a persistent splenomegaly. Clinical examination and laboratory testing evidenced the following: splenomegaly, hepatomegaly, anaemia, leukopenia and neutropenia, thrombocytopenia, and a myelogram showing Gaucher cells. In this context, the suspicion of Gaucher disease was raised and the investigations were further completed through specific enzyme testing and genetic testing. The low values of lysosomal enzymes, coupled with the detection of two specific genetic mutations confirmed the diagnosis of Gaucher disease.In January 2017, treatment with 2400U of imiglucerase in intravenous perfusion every two weeks was begun.

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RESPONSE TO ENZYME REPLACEMENT THERAPY IN PATIENTS WITH GAUCHER DISEASE TYPE I

10.36295/asro.2019.220613 ◽

2019 ◽

Vol 22 (06) ◽

pp. 103-117

Author(s):

Mays Al-Tai ◽

Deia Al-Asady ◽

Rula Hamid

Keyword(s):

Enzyme Replacement Therapy ◽

Replacement Therapy ◽

Gaucher Disease ◽

Disease Type ◽

Type I ◽

Enzyme Replacement

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Ghrelin, leptin and adiponectin levels in Gaucher disease type I patients on enzyme replacement therapy

Clinical Nutrition ◽

10.1016/j.clnu.2014.08.010 ◽

2015 ◽

Vol 34 (4) ◽

pp. 727-731 ◽

Cited By ~ 6

Author(s):

Divair Doneda ◽

André L. Lopes ◽

Bruno C. Teixeira ◽

Suzana D. Mittelstadt ◽

Cileide C. Moulin ◽

...

Keyword(s):

Enzyme Replacement Therapy ◽

Replacement Therapy ◽

Gaucher Disease ◽

Disease Type ◽

Type I ◽

Enzyme Replacement

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Oral maintenance clinical trial with miglustat for type I Gaucher disease: switch from or combination with intravenous enzyme replacement

Blood ◽

10.1182/blood-2007-02-075960 ◽

2007 ◽

Vol 110 (7) ◽

pp. 2296-2301 ◽

Cited By ~ 75

Author(s):

Deborah Elstein ◽

Altoon Dweck ◽

Drorit Attias ◽

Irith Hadas-Halpern ◽

Shoshana Zevin ◽

...

Keyword(s):

Gaucher Disease ◽

Pharmacokinetic Profile ◽

Disease Type ◽

Type I ◽

Open Label ◽

Enzyme Replacement ◽

Clinical Endpoints ◽

Gaucher Disease Type 1 ◽

Chitotriosidase Activity

Enzyme replacement therapy (ERT) with imiglucerase reduces hepatosplenomegaly and improves hematologic parameters in Gaucher disease type 1 within 6-24 months. Miglustat reduces organomegaly, improves hematologic parameters, and reverses bone marrow infiltration. This trial evaluates miglustat in patients clinically stable on ERT. Tolerability of miglustat and imiglucerase, alone and in combination, pharmacokinetic profile, organ reduction, and chitotriosidase activity were assessed. Thirty-six patients stable on imiglucerase were randomized into this phase II, open-label trial. Statistically significant changes from baseline were assessed (paired t test) on primary objectives with secondary analyses on biochemical and safety parameters. Liver and spleen volume were unchanged in switched patients. No significant differences were seen between groups regarding mean change in hemoglobin. Mean change in platelet counts was only significant between miglustat and imiglucerase groups (P = .035). Chitotriosidase activity remained stable. In trial extension, clinical endpoints were generally maintained. Miglustat was well tolerated alone or in combination. Miglustat's safety profile was consistent with previous trials; moreover, no new cases of peripheral neuropathy were observed. Gaucher disease type 1 (GD1) parameters were stable in most switched patients. Combination therapy did not show benefit. Findings suggest miglustat could be an effective maintenance therapy in stabilized patients with GD1.

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REDUCED DOSING REGIMEN OF ENZYME REPLACEMENT THERAPY IN ADULT PATIENTS WITH TYPE I GAUCHER DISEASE: PRELIMINARY RESULTS

Hematology and Transfusiology ◽

10.35754/0234-5730-2019-64-3-331-341 ◽

2019 ◽

Vol 64 (3) ◽

pp. 331-341 ◽

Cited By ~ 1

Author(s):

R. V. Ponomarev ◽

K. A. Lukina ◽

E. P. Sysoeva ◽

R. B. Chavynchak ◽

A. A. Solovyeva ◽

...

Keyword(s):

Enzyme Replacement Therapy ◽

Replacement Therapy ◽

Gaucher Disease ◽

Lysosomal Storage Diseases ◽

Adult Patients ◽

Type I ◽

Treatment Goals ◽

Lysosomal Storage ◽

Current Standard ◽

Enzyme Replacement

Introduction. Gaucher disease (GD) belongs to the group of lysosomal storage diseases. Enzyme replacement therapy (ERT) is considered to be the current standard in GD treatment. No reduced ERT regimen has thus far been developed. Aim. To develop an optimal reduced ERT regimen for adult patients with type I GD, which is scientifically and economically viable.Materials and methods. The study included 100 adult patients with type I GD who achieved treatment goals following at least two years of the standard ERT regimen. Patients were prescribed a reduced ERT regimen, which consisted in increasing the interval between the infusions of the recombinant enzyme up to 4 weeks, at a dose of 15–20 units/kg of body weight. The efficacy of the reduced ERT regimen was assessed once every 12 months according to main GD parameters. The follow-up period in the study ranged from 12 to 36 months.Results. The patients with type I GD who achieved treatment goals following the standard ERT regimen and were then prescribed a reduced ERT regimen retained a stable therapeutic effect of the initial treatment according to all parameters: no clinically significant differences found in haemoglobin and platelet levels, spleen size and specific infiltration of femur bone marrow.Conclusion. An increase in the intervals between infusions of the recombinant glucocerebrosidase up to 4 weeks for 12, 24 and 36 months did not lead to worsening of the laboratory and instrumental parameters associated with GD.

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Finding and Treating Gaucher Disease Type 1 – The Role of the Haematologist

European Oncology & Haematology ◽

10.17925/eoh.2018.14.1.50 ◽

2018 ◽

Vol 14 (1) ◽

pp. 50

Author(s):

Maria-Domenica Cappellini ◽

Elena Cassinerio ◽

Irene Motta ◽

William Morello ◽

Jesús Villarubia

Keyword(s):

Gaucher Disease ◽

Clinical Symptoms ◽

Genetic Disorder ◽

Diagnostic Delay ◽

Screening Tools ◽

Substrate Reduction Therapy ◽

Lysosomal Storage ◽

Ashkenazi Jews ◽

Enzyme Replacement

Gaucher disease (GD) type 1 is the most common lysosomal storage disease and the most common genetic disorder among Ashkenazi Jews. The majority of patients with GD present with unexplained splenomegaly and/or thrombocytopenia, and the disorder often affects children; consequently, haematologists and paediatricians are ideally placed to diagnose this condition. Prompt management of GD type 1 using enzyme-replacement therapy or substrate reduction therapy can reduce the risk of developing long-term GD complications and reverse many of the initial signs/symptoms, thereby improving both quality and duration of life. Treatment is most effective when initiated early; consequently, a prompt diagnosis is essential. Despite this, the average time to diagnosis following the onset of clinical symptoms is 4 years. Reasons for the delay include the heterogeneous nature of the disease, together with a lack of awareness of rare haematological disorders and the benefits of early treatment. Indeed, studies show that only 20% of haematologists consider GD type 1 in their differential diagnosis for patients presenting with splenomegaly and/or thrombocytopenia. To help raise awareness of GD, reduce the diagnostic delay and prevent unnecessary tissue biopsies, simple diagnostic algorithms and screening tools have been developed and validated, both in adults and in children.

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Mass Spectrometry Evaluation of Biomarkers in the Vitreous Fluid in Gaucher Disease Type 3 with Disease Progression Despite Long-Term Treatment

Diagnostics ◽

10.3390/diagnostics10020069 ◽

2020 ◽

Vol 10 (2) ◽

pp. 69

Author(s):

Aizeddin Mhanni ◽

Michel Boutin ◽

Frank Stockl ◽

Janine Johnston ◽

Jeff Barnes ◽

...

Keyword(s):

Mass Spectrometry ◽

Visual Acuity ◽

Gaucher Disease ◽

Disease Type ◽

Substrate Reduction Therapy ◽

Lysosomal Storage ◽

High Concentration ◽

Enzyme Replacement ◽

Long Term Treatment ◽

Type 3

Intraocular lesions have been infrequently reported in patients with Gaucher disease type 3 (GD3). We previously reported siblings with GD3 who responded well to the combination of enzyme replacement therapy (ERT) and substrate reduction therapy (SRT). Here we report progressive bilateral vitreous and preretinal deposits with declining visual acuity requiring bilateral vitrectomies in one of these siblings. These ocular manifestations had progressed despite combined ERT and SRT with improvement in visual acuity after vitrectomies. Vitrectomy fluid analysis performed for the first time by ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) identified a high concentration of glucosylceramide (GluCer) in the patient (262.842 nM) compared to a sample (0.428 nM from a patient without a lysosomal storage or known hereditary metabolic disorder). The GluCer detected in our patient was resolved into 12 different isoforms including two methylated ones. No evidence of galactosylceramide (GalCer) was detected. The development of these intraocular manifestations and their characterization by UPLC-MS/MS indicate a need for ongoing ophthalmologic evaluation of all GD patients and for new therapies that can cross the blood–retinal and blood–brain barriers for patients with GD and other neuropathic lysosomal storage disorders.

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Ophthalmic manifestations of Gaucher disease: the most common lysosomal storage disorder

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2018-312846 ◽

2019 ◽

Vol 103 (3) ◽

pp. 315-326 ◽

Cited By ~ 5

Author(s):

Aaron W Winter ◽

Ali Salimi ◽

Luis H Ospina ◽

Jonathan C P Roos

Keyword(s):

Gaucher Disease ◽

Substrate Reduction Therapy ◽

Type I ◽

Lysosomal Storage ◽

Ocular Abnormalities ◽

Enzyme Replacement ◽

Ocular Manifestations ◽

Ophthalmic Manifestations ◽

Increased Risk ◽

Risk Of Malignancy

Gaucher disease (GD) results from a deficiency of glucocerebrosidase activity and the subsequent accumulation of the enzyme’s metabolites, principally glucosylsphingosine and glucosylceramide. There are three principal forms: Type I, which is the most common, is usually considered non-neuronopathic. Type II, III and IIIc manifest earlier and have neurological sequelae due to markedly reduced enzyme activity. Gaucher’s can be associated with ophthalmological sequelae but these have not been systematically reviewed. We therefore performed a comprehensive literature review of all such ophthalmic abnormalities associated with the different types of Gaucher disease. We systematically searched the literature (1950 – present) for functional and structural ocular abnormalities arising in patients with Gaucher disease and found that all subtypes can be associated with ophthalmic abnormalities; these range from recently described intraocular lesions to disease involving the adnexae, peripheral nerves and brain. In summary, Gaucher can affect most parts of the eye. Rarely is it sight-threatening; some but not all manifestations are amenable to treatment, including with enzyme replacement and substrate reduction therapy. Retinal involvement is rare but patients with ocular manifestations should be monitored and treated early to reduce the risk of progression and further complications. As Gaucher disease is also associated with Parkinsons disease and may also confer an increased risk of malignancy (particularly haematological forms and melanoma), any ocular abnormalities should be fully investigated to exclude these potential underlying conditions.

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