Child ; Humans ; Gaucher Disease/therapy*

Child ; Consensus ; Gaucher Disease/therapy* ; Humans

No abstract available.
Adult ; Anticonvulsants/therapeutic use ; Bone Marrow/*pathology ; Epilepsies, Myoclonic/complications/*diagnosis/drug therapy ; Female ; Gaucher Disease/complications/*diagnosis/drug therapy ; Glucosylceramidase/genetics/therapeutic use ; Humans ; Phenotype ; Point Mutation ; Recurrence

PURPOSE: Gaucher disease (GD) is the most common lysosomal storage disease caused by beta-glucocerebrosidase (GBA) deficiency. Oral substrate reduction therapy with miglustat (Zavesca®) was approved for the treatment of adults with GD type 1, for whom enzyme replacement therapy (ERT) is unsuitable or not a therapeutic option. In this study, we report the effect of miglustat (Zavesca®) in three Korean GD patients. MATERIALS AND METHODS: Clinical findings comprising age at diagnosis, presenting signs, laboratory findings at diagnosis, GBA activity and mutations, and clinical courses of the three patients were reviewed. RESULTS: Miglustat was administered to three patients who reported allergic reactions during intravenous imiglucerase infusions. One patient withdrew after 15 months of miglustat administration owing to continuous elevation of disease biomarker levels (chitotriosidase, acid phosphatase, and angiotensin-converting enzyme). Poor adherence to medication was suspected but was denied by the patient. In the other two patients, platelet count and levels of hemoglobin and other biomarkers remained stable during miglustat administration. However, they suffered from severe diarrhea and weight loss, which led to miglustat discontinuation after 1 and 12 months of administration. CONCLUSION: Our study shows that although miglustat is suggested to GD patients as an alternative treatment to ERT, significant adverse reactions may lead to discontinuation of miglustat. In addition, it is difficult to monitor the drug adherence.
Acid Phosphatase ; Adult ; Biomarkers ; Diagnosis ; Diarrhea ; Enzyme Replacement Therapy ; Gaucher Disease* ; Glucosylceramidase ; Humans ; Hypersensitivity ; Lysosomal Storage Diseases ; Platelet Count ; Weight Loss

Gaucher disease type 1 (GD1) is an inherited lysosomal storage disorder caused by deficiency of acid β-glucosidase. The diminished enzyme activity leads to the accumulation of substrates and results in multi-systemic manifestations including hepatosplenomegaly, anemia, thrombocytopenia, and bone diseases. Enzyme replacement therapy (ERT) by infusion of recombinant protein has been the standard treatment for over 20 years. Despite the successful long-term treatment with ERT, several unmet needs remain in the treatment of GD1 such as severe pulmonary and skeletal manifestations. Substrate reduction therapy (SRT) reduces the accumulation of substrates by inhibiting their biosynthesis. Eliglustat, a new oral SRT, was approved in United States and Europe as a first-line therapy for treating adult patients with GD1 who have compatible CYP2D6 metabolism phenotypes. Although eliglustat is not yet available in Korea, introduction and summary of this new treatment modality are provided in this paper by review of literatures. Despite the fact that there are only limited studies to draw resolute conclusions, the current data demonstrated that eliglustat is not inferior to ERT in terms of its clinical efficacy. The approval of eligustat enables eligible adult GD1 patients to have the option of oral therapy although it still needs further studies on long-term outcomes. The individual patient should be assessed carefully for the choice of treatment modality when eliglustat becomes available in Korea. Furthermore, the clinical guidelines for Korean patients with GD1 regarding the use of eliglustat needs to be developed in near future.
Adult ; Anemia ; Bone Diseases ; Cytochrome P-450 CYP2D6 ; Enzyme Replacement Therapy ; Europe ; Gaucher Disease* ; Humans ; Korea ; Metabolism ; Phenotype ; Thrombocytopenia ; Treatment Outcome ; United States

Gaucher disease is a lysosomal storage disease for which enzyme replacement therapy has proven to be effective. A switch-over clinical trial was performed to evaluate the efficacy and safety of Abcertin(R) (ISU Abxis, Seoul, Korea) in subjects with type 1 Gaucher disease who were previously treated with imiglucerase. Five Korean patients with type 1 Gaucher disease were enrolled. Previous doses of imiglucerase ranged from 30 to 55 U/kg every other week. The same dose of Abcertin(R) was administered to all patients for 24 weeks. Primary efficacy endpoints were changes in hemoglobin levels and platelet counts, and the secondary efficacy endpoints included changes in liver and spleen volumes, serum biomarkers, skeletal status and bone mineral density (BMD). During the study period, no statistically significant changes were observed in all parameters including hemoglobin levels and platelet counts, liver and spleen volumes, skeletal status and BMD. Abcertin(R) administration was continued in three patients for another 24 weeks as an extension of the study. Hemoglobin levels and platelet counts were maintained in all three patients. In conclusion, the efficacy and safety of Abcertin(R) are similar to those of imiglucerase, and Abcertin(R) is an effective therapeutic agent for patients with type 1 Gaucher disease (Clinical Trial Registry No. NCT02053896 at www.clinicaltrials.gov).
Adolescent ; Adult ; Biosimilar Pharmaceuticals/adverse effects/pharmacokinetics/*therapeutic use ; Child ; *Enzyme Replacement Therapy/adverse effects ; Female ; Gaucher Disease/blood/*drug therapy ; Glucosylceramidase/adverse effects/pharmacokinetics/*therapeutic use ; Humans ; Male ; Recombinant Proteins/adverse effects/pharmacokinetics/*therapeutic use

OBJECTIVETo explore the efficacy of unrelated umbilical cord blood transplantation (UCBT) in the treatment of Gaucher disease.

METHODThe clinical characteristics of three children with Gaucher disease underwent UCBT in our hospital between April 2013 and September 2014 were retrospectively analyzed. Literature on allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of Gaucher disease was searched at Wanfang and Pubmed databases between 1983 and 2015 and was reviewed and summaried.

RESULTThree children with Gaucher disease, all were female, received UCBT. These patients' age at receiving transplantation was 3.8 years, 7.1 years and 2.6 years, respectively. The second case received the second transplantation. The first and third case received splenectomy before UCBT. The pretreatment regimen was busulfan (Bu)/fludarabine (Flu)/cyclophosphamide (CTX)/antithymocyte globulin (ATG), and for the patient received the second transplantation melphalan was added to the myeloablative conditioning regimen of Bu/Flu/CTX/ATG. Cyclosporine and mycophenolate mofetil (MMF) wee used for prophylaxis of acute graft versus host disease (aGVHD). The dose of cord blood stem cell nucleated cell counts was 9.7 × 10⁷ /kg,11.9 × 10⁷ /kg and 7.6 × 10⁷/kg respectively. The dose of cord blood stem cell CD34⁺ cell counts was 5.4 × 10⁵/kg , 3.5 × 10⁵/kg and 3.2 × 10⁵/kg respectively. The day of granulocytes exceeding 0.5 × 10⁹/L was day 11, 12 and 19 after transplantation, respectively. The day of platelets exceeding 20 × 10⁹/L was day 14, 33 and 74 after transplantation, respectively. At one month after transplantation the rate of chimerism was over 95% and all patients got donor complete chimerism. The level of β-glucocerebrosidase recovered to normal at one month after transplantation. During transplantation, all patients developed cytomegalovirus (CMV) and Epstein-Barr virus (EBV) viremia. In case 1 immune thrombocytopenia occurred at five month after transplantation unresponding to steroids and mesenchymal stem cells infusion was administered and his platelet in routine blood test recovered to normal. But the patient died because she was infected with varicella-zoster virus out of hospital at nine month after transplantation and the level of β-glucocerebrosidase was normal before death and chronic GVHD (cGVHD) was not found. The case 2 is now in 19th month after transplantation and his level of β-glucocerebrosidase was normal. cGVHD was not found. The patient is currently free of disease. The case 3 was in 9th month after transplantation and his level of β-glucocerebrosidase was normal. cGVHD was found at 112 day after transplantation and was localized and could be controlled by hormonal therapy. The patient is currently free of disease. Three patients' size of liver was significantly reduced after their level of β-glucocerebrosidase ecovered. There were 50 cases with Gaucher disease who were treated with allo-HSCT in the literature and none of them were reported from China. Disease-free survival rate of patients treated with allo-HSCT for Gaucher disease was 85%. In all reports, there were 31 cases who had information of typing of Gaucher disease, of whom 22 cases had type 1 and 9 cases had type 3. Twenty-nine cases had information of survival, of whom 24 cases survived and 5 cases died of infection. Fifteen cases had data of engraftment, 2 of whom had graft failure and one had late graft failure.Glucocerebrosidase recovered to normal in 25 of 31 cases who had relevant data, in one of whom with late graft failure the enzyme recovered to normal 3 month after transplantation, but his enzyme decreased to the initial level 9 month after transplantation. Along with enzyme level's recovery to normal, in a part of cases bone pain and hepatomegaly were relieved and growth delay was improved.

CONCLUSIONThe unrelated UCBT may be a form of treatment that offers the potential of permanent cure and a procedure with possible long-term benefits in patients with Gaucher disease.

Antilymphocyte Serum ; therapeutic use ; Busulfan ; therapeutic use ; Child ; Child, Preschool ; China ; Cyclophosphamide ; therapeutic use ; Cyclosporine ; therapeutic use ; Disease-Free Survival ; Female ; Gaucher Disease ; therapy ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Mycophenolic Acid ; analogs & derivatives ; therapeutic use ; Retrospective Studies ; Transplantation Conditioning ; Vidarabine ; analogs & derivatives ; therapeutic use

China ; Forecasting ; Gaucher Disease ; diagnosis ; therapy ; Humans ; Rare Diseases

The recent years have seen great advances in reversal of programming of differentiated somatic cells towards pluripotency by methods not involving nuclear transfer. Although differentiation of cells involves complex genetic and epigenetic changes, it is now possible to generate cells with many properties of pluripotent embryonic stem cells by transduction of differentiated cells with only four transcription factors: Oct3/4, Sox2, Klf4 and c-Myc. In advance, the protocol for improving the efficiency of generating induced pluripotent stem(iPS) cells and establishing clinically applicable cells has been developed. Recently, the generation of iPS cells from patients with a variety of genetic diseases with either Mendelian or complex inheritance including X-linked adrenoleukodystrophy, amyotrophic lateral sclerosis, Duchenne and Becker muscular dystrophy, Parkinson's disease, Huntington's disease, Gaucher disease type III, Down syndrome is also possible. Such disease-specific iPS cells offer an unprecedented opportunity to recapitulate both normal and pathologic human tissue formation in vitro, thereby enabling disease investigation, drug development and cell therapy.
Adrenoleukodystrophy ; Amyotrophic Lateral Sclerosis ; Down Syndrome ; Embryonic Stem Cells ; Epigenomics ; Gaucher Disease ; Humans ; Huntington Disease ; Induced Pluripotent Stem Cells ; Muscular Dystrophy, Duchenne ; Parkinson Disease ; Tissue Therapy ; Transcription Factors ; Wills

OBJECTIVEGaucher disease is the most common lysosomal storage disorder. A deficiency of beta-glucocerebrosidase causes accumulation of the glucocerebroside in macrophages throughout the body. This study summarizes the effects of enzyme replacement therapy (ERT) with Imiglucerase in children with Gaucher disease.

METHODSData from 72 patients (46 were male and 26 female, age ranged from 16 months to 22 years, median 8 years and 8 months) who were treated in the hospital between May 1999 and October 2005 were collected and analyzed, 57 of the patients had type 1 Gaucher disease, 2 patients with type 2, and 13 patients with type 3. Twenty-two patients had undergone total splenectomy. Imiglucerase was given at an initial dose 60 U/kg body weight by intravenous infusion every 2 weeks. The dose was reduced to 45 U/kg when they had achieved the specified therapeutic goals after 2 years. Clinical outcome data of Imiglucerase treatment were collected using routine Gaucher clinical measures, including growth, hematology, liver and spleen 3-dimensional measurements, and skeletal assessments every 3 - 6 months.

RESULTSThree patients were lost to follow-up, 4 patients died, and 65 patients continued to receive the therapy. Hemoglobin and platelet levels of the patients with intact spleen increased most rapidly from the first 12 months of ERT (P < 0.01). Hemoglobin level of the patients who had undergone splenectomy determined at 30 months of treatment was higher than that of baseline (P < 0.01), but platelet levels were not significantly different (P > 0.05). The volumes of the liver decreased after the 6 months of ERT, decreased in average by (39 +/- 17)% at 24 months (P < 0.01). The volumes of spleen decreased after the 12 months of ERT by (59 +/- 21)% at 24 months (P < 0.01). During the first 12 month, the height and weight of the patients who were 2 - 12 years old increased (8.6 +/- 4.3) cm and (2.6 +/- 1.7) kg, respectively, and those of the patients who were 12 - 18 years old increased (5.2 +/- 3.9) cm and (4.5 +/- 3.3) kg, separately. Bone pain reported by 16 patients relieved after 3 months of treatment. But radiological evidence of bone disease did not change. The signs and symptoms of CNS involvement in patients with type 2 and type 3 disease were not improved. No serious adverse events were reported.

CONCLUSIONSERT with Imiglucerase could improve the quality of life of the patients with Gaucher disease by ameliorating the Gaucher disease-associated anemia, thrombocytopenia, organomegaly, growth retardation and bone pain.

Adolescent ; Anemia ; enzymology ; Child ; Child, Preschool ; Enzyme Replacement Therapy ; adverse effects ; methods ; Female ; Gaucher Disease ; drug therapy ; enzymology ; physiopathology ; Glucosylceramidase ; administration & dosage ; adverse effects ; deficiency ; therapeutic use ; Growth Disorders ; enzymology ; Hepatomegaly ; enzymology ; Humans ; Infant ; Male ; Recombinant Proteins ; therapeutic use ; Retrospective Studies ; Splenomegaly ; enzymology ; Thrombocytopenia ; enzymology ; Treatment Outcome ; Young Adult