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Evaluation of bone infiltration of skull base in Gaucher disease
S26
Abstracts
biopsy was orange in color with fibrous bands that delineated wellformed nodules, giving a pattern of cirrhosis with prominent microvesicular lipid deposition, and enlarged foamy macrophages. A sixth biopsy was obtained at age 24 years, when AST and ALT were 115 U/L and 136 U/L, respectively. The biopsy showed portal tract fibrous expansion, bridging fibrosis and very focal isolated islands of entrapped hepatic parenchyma and resultant nodule formation (micronodular cirrhosis). Parenchymal hepatocytes had extensive microvesicular steatosis, ceroid laden foamy macrophages without bile duct proliferation. This series of six liver biopsies illustrates the early childhood onset and progressive nature of liver disease in a CESD patient, despite simvastatin use. The depictions of six liver biopsies spanning over two decades may facilitate histopathologic recognition of this underrecognized lysosomal disease, which is crucial since enzyme replacement therapy is available in clinical trials. doi:10.1016/j.ymgme.2013.12.039
28 Evaluation of bone infiltration of skull base in Gaucher disease Debora Bertholdoa, Filippo Vairob, Ana Paula Vanzb, Leticia Salvib, Cristina Nettob, Livia Paskulinb, Matheus Camargob, Leonardo Vedolinb,c, Ida Schwartzb, aDAPI - Diagnóstico Avançado por Imagem, Curitiba, Brazil, bHospital de Clínicas de Porto Alegre, Porto Alegre, Brazil, cHospital Moinhos de Vento, Porto Alegre, Brazil Bone abnormalities in Gaucher disease (GD) result from the infiltration of the bone marrow by Gaucher cells, and consequent mechanical obstruction and reduced blood flow, causing bone necrosis and hemorrhage. Magnetic resonance imaging (MRI) is a semiquantitative method to evaluate bone marrow infiltration. No reports on infiltration of bone marrow in skull base in GD patients have been published to date. Bone marrow infiltration was analyzed using MRI on clivus and odontoid in patients with GD from the Reference Center of RS, Brazil. Sixteen patients (type I GD = 15; type III GD = 1) with a mean age of 35.4 years were studied and compared to 11 controls with a mean age of 35.3 years. A three-dimensional, T1-weighted, gradient-echo sequence (MPRAGE, 3D TFE) was obtained for each patient, and was analyzed by two radiologists regarding the degree of infiltration. Three different ROIs were drawn: on the clivus (region of interest - ROI1), odontoid process ROI2) and frontal bone (ROI3). Patients with GD showed BMB average score of 7.3 (range 0-13). The degree of infiltration, measured by the ratio between ROIs (ROI1/ROI2; ROI2/ROI 3 and ROI1/ROI3) was significantly higher in patients than in the control group compared to the infiltration of the clivus/frontal bone (p = 0.03) and odontoid/frontal bone (p = 0.007). There are different scores to evaluate bone infiltration in GD, the most used is BMB score that analyze lumbar spine and femur.
However, little is known about infiltration of skull base and cervical spine. In patients with bilateral prosthetic femoral head or restrictions for the CABG lower limbs such an assessment cannot be performed. Based on our data, we can say that the evaluation of cranial bone infiltration is a sensitive method to assess the degree of bone erosion in patients with GD.
doi:10.1016/j.ymgme.2013.12.040
29 Monitoring of Gaucher disease type 1 in presymptomatic pediatric patients Louise Bier, Amy Yang, Khyati Desai, Jessica Cohen-Pfeffer, Robert J. Desnick, Manisha Balwani, Icahn School of Medicine at Mount Sinai, New York, NY, USA The aim of this study is to characterize early manifestations of type 1 Gaucher disease (GD) in presymptomatic pediatric patients who were diagnosed by genetic testing, in order to inform guidelines for monitoring. All patients’ parents were known GBA carriers ascertained through the Jewish Genetic Disease screening program. Patients were diagnosed by molecular genetic testing prenatally or before the age of three and were evaluated at baseline and on sequential follow-up. Data from clinical, laboratory and imaging assessments were used to monitor disease progression. Thirty patients (14 males, 16 females), age 1 to 15 years (mean age at last follow-up 6 years), were evaluated at baseline and on follow-up. This cohort includes 27 N370S homozygotes and 3 compound heterozygotes for N370S/R496H. Ninety percent of patients (27) did not have clinically significant GD manifestations. Ten patients (33%) reported nonspecific symptoms such as mild bone/joint pain and easy bruising/bleeding. Laboratory evaluation of 29 patients revealed transient anemia (likely due to iron deficiency) and transient thrombocytopenia in 6 and 5 patients (21% and 17%), respectively. Some degree of liver or spleen enlargement was observed in 15 of 18 patients (83%) who underwent radiologic imaging (abdominal ultrasound or MRI); however, organ volumes calculated in multiples of normal (MN) varied significantly over time, most likely due to interval growth. Chitotriosidase activity levels varied markedly among patients (5 to 5072 nmol/hr/ml) and tended to increase with age. Most patients (93%) had no evidence of growth retardation. Three patients (10%) experienced clinically significant symptoms requiring additional follow-up. One 10-year old patient, monitored regularly from 4 months of age, had progressive splenomegaly (from 3.2 to 10.0 MN) and no interval growth in the previous year, and was started on enzyme replacement therapy. Additionally, two other patients, a 6-year old female with borderline platelets (146,000 u/L) and moderate splenomegaly on USG, and a 5year old male with mild splenomegaly, growth delay and persistent thrombocytopenia (60,000-83,000 u/L), are being monitored closely. Gaucher disease manifestations in our cohort of presymptomatic children (N370S/N370S and N370S/R496H) include mild to moderate visceromegaly, abnormal blood counts, and biomarker elevation. In most cases, these abnormalities were not clinically significant. However, these data suggest that even patients with these “mild” genotypes can have early progression of GD related manifestations and should be monitored during childhood. Although guidelines exist for monitoring type 1 GD pediatric patients, these are applicable to the more severe genotypes which typically manifest in childhood. Based on our experience, in patients homozygous for the N370S mutation, a limited schedule of assessments can be used in childhood to detect early manifestations.
doi:10.1016/j.ymgme.2013.12.041
Abstracts
biopsy was orange in color with fibrous bands that delineated wellformed nodules, giving a pattern of cirrhosis with prominent microvesicular lipid deposition, and enlarged foamy macrophages. A sixth biopsy was obtained at age 24 years, when AST and ALT were 115 U/L and 136 U/L, respectively. The biopsy showed portal tract fibrous expansion, bridging fibrosis and very focal isolated islands of entrapped hepatic parenchyma and resultant nodule formation (micronodular cirrhosis). Parenchymal hepatocytes had extensive microvesicular steatosis, ceroid laden foamy macrophages without bile duct proliferation. This series of six liver biopsies illustrates the early childhood onset and progressive nature of liver disease in a CESD patient, despite simvastatin use. The depictions of six liver biopsies spanning over two decades may facilitate histopathologic recognition of this underrecognized lysosomal disease, which is crucial since enzyme replacement therapy is available in clinical trials. doi:10.1016/j.ymgme.2013.12.039
28 Evaluation of bone infiltration of skull base in Gaucher disease Debora Bertholdoa, Filippo Vairob, Ana Paula Vanzb, Leticia Salvib, Cristina Nettob, Livia Paskulinb, Matheus Camargob, Leonardo Vedolinb,c, Ida Schwartzb, aDAPI - Diagnóstico Avançado por Imagem, Curitiba, Brazil, bHospital de Clínicas de Porto Alegre, Porto Alegre, Brazil, cHospital Moinhos de Vento, Porto Alegre, Brazil Bone abnormalities in Gaucher disease (GD) result from the infiltration of the bone marrow by Gaucher cells, and consequent mechanical obstruction and reduced blood flow, causing bone necrosis and hemorrhage. Magnetic resonance imaging (MRI) is a semiquantitative method to evaluate bone marrow infiltration. No reports on infiltration of bone marrow in skull base in GD patients have been published to date. Bone marrow infiltration was analyzed using MRI on clivus and odontoid in patients with GD from the Reference Center of RS, Brazil. Sixteen patients (type I GD = 15; type III GD = 1) with a mean age of 35.4 years were studied and compared to 11 controls with a mean age of 35.3 years. A three-dimensional, T1-weighted, gradient-echo sequence (MPRAGE, 3D TFE) was obtained for each patient, and was analyzed by two radiologists regarding the degree of infiltration. Three different ROIs were drawn: on the clivus (region of interest - ROI1), odontoid process ROI2) and frontal bone (ROI3). Patients with GD showed BMB average score of 7.3 (range 0-13). The degree of infiltration, measured by the ratio between ROIs (ROI1/ROI2; ROI2/ROI 3 and ROI1/ROI3) was significantly higher in patients than in the control group compared to the infiltration of the clivus/frontal bone (p = 0.03) and odontoid/frontal bone (p = 0.007). There are different scores to evaluate bone infiltration in GD, the most used is BMB score that analyze lumbar spine and femur.
However, little is known about infiltration of skull base and cervical spine. In patients with bilateral prosthetic femoral head or restrictions for the CABG lower limbs such an assessment cannot be performed. Based on our data, we can say that the evaluation of cranial bone infiltration is a sensitive method to assess the degree of bone erosion in patients with GD.
doi:10.1016/j.ymgme.2013.12.040
29 Monitoring of Gaucher disease type 1 in presymptomatic pediatric patients Louise Bier, Amy Yang, Khyati Desai, Jessica Cohen-Pfeffer, Robert J. Desnick, Manisha Balwani, Icahn School of Medicine at Mount Sinai, New York, NY, USA The aim of this study is to characterize early manifestations of type 1 Gaucher disease (GD) in presymptomatic pediatric patients who were diagnosed by genetic testing, in order to inform guidelines for monitoring. All patients’ parents were known GBA carriers ascertained through the Jewish Genetic Disease screening program. Patients were diagnosed by molecular genetic testing prenatally or before the age of three and were evaluated at baseline and on sequential follow-up. Data from clinical, laboratory and imaging assessments were used to monitor disease progression. Thirty patients (14 males, 16 females), age 1 to 15 years (mean age at last follow-up 6 years), were evaluated at baseline and on follow-up. This cohort includes 27 N370S homozygotes and 3 compound heterozygotes for N370S/R496H. Ninety percent of patients (27) did not have clinically significant GD manifestations. Ten patients (33%) reported nonspecific symptoms such as mild bone/joint pain and easy bruising/bleeding. Laboratory evaluation of 29 patients revealed transient anemia (likely due to iron deficiency) and transient thrombocytopenia in 6 and 5 patients (21% and 17%), respectively. Some degree of liver or spleen enlargement was observed in 15 of 18 patients (83%) who underwent radiologic imaging (abdominal ultrasound or MRI); however, organ volumes calculated in multiples of normal (MN) varied significantly over time, most likely due to interval growth. Chitotriosidase activity levels varied markedly among patients (5 to 5072 nmol/hr/ml) and tended to increase with age. Most patients (93%) had no evidence of growth retardation. Three patients (10%) experienced clinically significant symptoms requiring additional follow-up. One 10-year old patient, monitored regularly from 4 months of age, had progressive splenomegaly (from 3.2 to 10.0 MN) and no interval growth in the previous year, and was started on enzyme replacement therapy. Additionally, two other patients, a 6-year old female with borderline platelets (146,000 u/L) and moderate splenomegaly on USG, and a 5year old male with mild splenomegaly, growth delay and persistent thrombocytopenia (60,000-83,000 u/L), are being monitored closely. Gaucher disease manifestations in our cohort of presymptomatic children (N370S/N370S and N370S/R496H) include mild to moderate visceromegaly, abnormal blood counts, and biomarker elevation. In most cases, these abnormalities were not clinically significant. However, these data suggest that even patients with these “mild” genotypes can have early progression of GD related manifestations and should be monitored during childhood. Although guidelines exist for monitoring type 1 GD pediatric patients, these are applicable to the more severe genotypes which typically manifest in childhood. Based on our experience, in patients homozygous for the N370S mutation, a limited schedule of assessments can be used in childhood to detect early manifestations.
doi:10.1016/j.ymgme.2013.12.041