Diagnosis features of pediatric Gaucher disease patients in the era of enzymatic therapy, a national-base study from the Spanish Registry of Gaucher Disease

被引：25

作者：

Andrade-Campos, Marcio ^{[1
,2
,3
]}

Alfonso, Pilar ^{[2
,3
]}

Irun, Pilar ^{[2
,3
]}

Armstrong, Judith ^{[4
]}

Calvo, Carmen ^{[5
]}

Dalmau, Jaime ^{[6
]}

Domingo, Maria-Rosario ^{[7
]}

Barbera, Jose-Luis ^{[8
]}

Cano, Horacio ^{[9
]}

Fernandez-Galan, Maria-Angeles ^{[10
]}

Franco, Rafael ^{[11
]}

Gracia, Inmaculada ^{[12
]}

Gracia-Antequera, Miguel ^{[13
]}

Ibanez, Angela ^{[14
]}

Lendinez, Francisco ^{[15
]}

Madruga, Marcos ^{[16
]}

Martin-Hernandez, Elena ^{[17
]}

del Mar O'Callaghan, Maria ^{[18
]}

Perez del Soto, Alberto ^{[19
]}

Ruiz del Prado, Yolanda ^{[20
]}

Sancho-Val, Ignacio ^{[21
]}

Sanjurjo, Pablo ^{[22
]}

Pocovi, Miguel ^{[23
]}

Giraldo, Pilar ^{[1
,2
,3
,24
,25
]}

机构：

[1] Miguel Servet Univ Hosp, Haematol Dept, Zaragoza, Spain

[2] Inst Salud Carlos III, CIBER Enfermedades Raras CIBERER, Zaragoza, Spain

[3] Aragon Inst Hlth Res IISAragon, Traslat Res Unit, Zaragoza, Spain

[4] Hosp San Juan Dios, Barcelona, Spain

[5] San Jorge Hosp, Pediat Dept, Huesca, Spain

[6] La Fe Univ Hosp, Pediat Dept, Valencia, Spain

[7] Hosp Clinico Univ Virgen Arrixaca, Murcia, Spain

[8] Manises Hosp, Pediat Dept, Valencia, Spain

[9] Los Arcos Mar Menor Univ Hosp, Haematol Dept, Murcia, Spain

[10] Virgen del Puerto Plasencia, Hematol Dept, CCCCCCC Plasencia DEPT, Spain

[11] Punta Europa Hosp, Haematol Dept, Cadiz, Spain

[12] Miguel Servet Univ Hosp, Pediat Dept, Zaragoza, Spain

[13] Hosp Univ Doctor Peset, Valencia, Spain

[14] Complejo Hosp Albacete, Haematol Dept, Albacete, Spain

[15] Torrecardenas Hosp, Pediatr Dept, Almeria, Spain

[16] Hosp Univ Virgen Rocio, Neurol Dept, Seville, Spain

[17] 12 Octubre Univ Hosp, Pediatr Dept, Madrid, Spain

[18] Inst Recerca Pediat Hosp Sant Joan Deu IRP HSJD, CIBERER, Barcelona, Spain

[19] Virgen Rocio Univ Hosp, Haematol Dept, Seville, Spain

[20] Hosp San Millan & San Pedro, Pediatr Dept, La Rioja, Spain

[21] Alcaniz Hosp, Haematol Dept, Teruel, Spain

[22] Cruces Univ Hosp, Pediatr Dept, Bilbao, Spain

[23] Univ Zaragoza, Biochem & Mol & Cellular Biol Dept, Zaragoza, Spain

[24] Spanish Fdn Study & Therapy Gaucher Dis FEETEG, Zaragoza, Spain

[25] Hosp Univ Miguel Servet, Unidad Invest Traslac, Pta Baja, Paseo Isabel Catolica 1-3, Zaragoza 50009, Spain

来源：

ORPHANET JOURNAL OF RARE DISEASES | 2017年 / 12卷

关键词：

Children; Gaucher Disease; Enzymatic replacement therapy; REPLACEMENT THERAPY; BONE COMPLICATIONS; BETA-GLUCOSIDASE; MARKED ELEVATION; CHILDREN; TYPE-1; INTERVENTION; CONSEQUENCES; SPLENECTOMY; MANAGEMENT;

D O I：

10.1186/s13023-017-0627-z

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页数：9

共 38 条

[1] Expression and functional characterization of mutated glucocerebrosidase alleles causing Gaucher disease in Spanish patients [J].