Biomedical subjects

Aya Abrahamov

Publications and source records attributed to Aya Abrahamov.

10 recordsLinked to original sources

PubMed2006

Outcome of ten years' echocardiographic follow-up in children with Gaucher disease.

The non-neuronopathic form Gaucher disease, the most prevalent lysosomal storage disorder, is marked by tremendous phenotypic heterogeneity; cardio-pulmonary involvement is distinctly rare except in the most severely affected patients. With the advent of enzyme replacement therapy, most symptomatic patients will not suffer from lung disease. However, because of concern about pulmonary hypertension among adult patients exposed to enzyme replacement therapy, echocardiography has been recommended as an early warning system for routine follow-up of all patients, including children. The purpose of this study was to review the results of more than a decade of echocardiographic findings in children followed semi-annually in a large referral clinic in order to ascertain whether echocardiography as an early signal of pulmonary hypertension in children is appropriate. 330 echocardiographic examinations were performed in 71 children (276 patient follow-up years). Only four patients receiving enzyme therapy each had a single abnormal examination that upon repeat examination six months later reverted to within normal limits. There were no abnormal results among the untreated patients. Therefore, we feel comfortable with rescinding our recommendation with regard to routine echocardiographic examinations in children. At the present time we believe that a baseline examination to rule out abnormalities would be sufficient.

Adolescent↗

PubMed2005

Uncomplicated outcome after anesthesia for pediatric patients with Gaucher disease.

PURPOSE: The purpose of this retrospective review was to highlight clinical issues relating to anesthetic management in children who present with Gaucher disease-specific features that may impact on anesthetic management and surgical outcome. Previous reports have dealt primarily with neuronopathic forms where neurological dysfunction determined the mode of anesthesia. To date, no series of routine surgeries in pediatric patients with non-neuronopathic Gaucher disease has been published. METHODS: All surgeries performed in children with Gaucher retrospectively analyzed. RESULTS: There were 31 procedures under anesthesia in 15 pediatric patients. Twenty-seven of these (87%) involved either insertion or removal of a central venous catheter. There was no correlation between disease severity and the need for blood transfusion postoperatively [required in only eight cases (25.8%), including a total hip replacement]. No difficult intubations or other airway problems were recorded. Positioning of two patients, because of gibbus and prior to hip replacement, respectively, required special attention. CONCLUSIONS: We record our experience in surgeries in children with mild, non-neuronopathic type I and severe neuronopathic type III Gaucher disease, who had relatively short surgeries under general anesthesia. Attention to hematological parameters in particular can minimize postoperative bleeding, the most serious complication.

Adolescent↗

PubMed2005

Survey of hematological aspects of Gaucher disease.

Hematologists have classically been the treating physicians of patients with Gaucher disease, and today, despite both specific and symptomatic therapeutic advances, they remain at the forefront of specialists to whom patients with Gaucher disease present. It is therefore appropriate to review that has changed and what has remained the same in hematological signs and symptoms of the disease in the decade and a half since therapy has become available.

Anemia↗

PubMed2005

Phenotypic heterogeneity in patients with Gaucher disease and the N370S/V394L genotype.

Correlation between genotype and phenotype in Gaucher disease is limited. It is known that the most common mutation N370S is protective of neurological involvement, but for the V394L mutation, described as the fifth most common among Ashkenazi Jews, little data are available. This study reports all known patients from a large referral clinic and from the international registry with Gaucher disease who are documented to have the N370S/V394L genotype. Of 476 patients in the Gaucher Clinic, 7 patients (2.0%) had the N370S/V394L genotype; of 2,836 patients in the registry, there were 14 patients (0.8%) with this genotype. There was an overlap of 3 patients, making a total of 18 patients, reflecting the rarity of this genotype among the studied cohorts. Most of these patients had mild disease; only 8 patients required specific enzyme therapy, none was splenectomized. Only 3 patients had skeletal involvement, but other baseline parameters were very diverse. Although genotype-phenotype correlation in this case may be difficult, because the V394L mutation when seen in a compound heterozygote with a null allele results in neuronopathic disease, one cannot conclude that this mutation is protective of neuronopathic disease and hence this is important for counseling of at-risk populations.

Adolescent↗

PubMed2004

N-brain natriuretic peptide: correlation with tricuspid insufficiency in Gaucher disease.

NT-pro-brain natriuretic peptide (NT-proBNP) values are correlated with right ventricle dysfunction in pulmonary hypertension and have been recommended as a prognostic marker for symptomatic primary pulmonary hypertension. The purpose of this pilot study was to determine whether NT-proBNP values correlate with mild to moderate pulmonary hypertension in Gaucher disease. The NT-proBNP assay was performed on sera from patients with type I (non-neuronopathic) Gaucher disease who were known to have tricuspid insufficiency (TI) gradient values on echocardiography that were normal (TI<20 mmHg), borderline (TI=25-29 mmHg), or abnormal (TI>or= 30 mmHg) over time. There was a statistically significant correlation (p=0.05) between mean NT-proBNP values and TI gradient group: mean NT-proBNP for normal TI gradient (n=20 patients)=133.3 (range: 46-445)pg/ml; mean NT-proBNP for borderline TI gradient (n=17 patients)=288.7 (range: 81-1088)pg/ml; and mean NT-proBNP for elevated TI gradient (n=10 patients)=1034.2 (73-6703)pg/ml. Treatment status was not correlated with TI gradient or NT-proBNP values. Thus, in this pilot study of Gaucher disease that included patients with mild to moderate pulmonary hypertension, NT-proBNP was correlated with echocardiographic findings. Further studies will be required to ascertain if NT-proBNP can be used for diagnosis and monitoring of these patients.

Adolescent↗

PubMed2002

Gaucher disease: pediatric concerns.

Gaucher disease, the most prevalent lysosomal storage disorder, is inherited as an autosomal recessive condition. The gold standard for diagnosis is decreased acid beta-glucosidase activity in the lymphocytes or fibroblasts; molecular analysis of mutations allows for some prognostication of disease severity. Prenatal diagnosis and carrier testing for at-risk families are currently available. There is tremendous phenotypic heterogeneity in the non-neuronopathic form (type I), ranging from clinically asymptomatic to massive hepatomegaly, hypersplenism, growth retardation in children and extensive involvement of bone and lungs. Presence on one allele of the most common mutation, N370S, which is the most prevalent among Ashkenazi Jews for whom there is a predilection for Gaucher disease, is protective of neurological involvement. Some mutations, such as 84GG and IVS2+1, are associated with more severe disease manifestations when appearing as compound heterozygotes with N370S, but when occurring in the homozygous state are not compatible with life. Other mutations, such as L444P, are associated with severe non-neurological disease when occurring as compound heterozygotes with N370S, but when occurring in the homozygous state may be predictive of neurological disease of either acute (type II) or subacute (type III) forms. In the past decade, enzyme replacement therapy has become available which has resulted in a reduction in liver and spleen volume and consequently improved anemia and thrombocytopenia in most patients. It has also engendered catch-up growth in many children, induced improvement in lung involvement secondary to Gaucher disease, and to some extent ameliorated episodes of bone pain. By virtue of treatment, many children who may have been severely affected no longer need to undergo splenectomy to treat hypersplenism, and therefore they are not at risk of bone involvement consequent to the loss of the preferred reservoir for lipid-laden 'Gaucher cells'. However, enzyme treatment is ineffective in reversing neurological signs, requires a lifelong commitment to intravenous infusions, thereby reducing quality of life, and is relatively expensive for many national health schemes. Hence, alternative forms of treatment, such as substrate balance, are being explored. Symptomatic management, including orthopedic surgery, pain relief for bone pain and even splenectomy, still has importance for patients with Gaucher disease. In addition, there is the potential for bone marrow transplantation and, in the future, gene therapy to be curative, particularly for patients with the neuronopathic forms.

Child↗

PubMed2001

Spectrum of abdominal sonographic findings in 103 pediatric patients with Gaucher disease.

The purpose of this study was to catalogue spleen and liver features by US in a cohort of 103 pediatric patients with Gaucher disease, and to document response to enzyme replacement therapy by serial US examination. There were 42 boys and 61 girls, 2 were splenectomized. Forty-eight patients received enzyme replacement therapy (ERT). At presentation all patients evinced organomegaly and 4.9% had focal (splenic or hepatic) lesions (hypo- and hyper-echoic or mixed). Fifteen patients began ERT before 11 years of age. There was a mean liver volume reduction from 230 to 137% after 2 years of ERT, with further reduction of 91% up to 6 years later. Mean spleen volume reduction was 38.4% at 2 years of ERT and a further reduction to 40.8% at last evaluation. Fourteen children began ERT between ages 11 and 16 years. Mean liver reduction was from 230 to 124% at 2 years and further reduction to mean of 104% recently. Mean splenic reduction was 37.7% after 2 years of ERT, with a mean of 43.8% recently (mean 4.5 years later). Organ volume changes in untreated and treated children were documented by US which is the modality of choice for repeat measures in this population. Our results highlight the initial dramatic and then continued response to ERT in pediatric patients with Gaucher disease.

Adolescent↗

PubMedDate not supplied

Effect of enzyme replacement therapy on gammopathies in Gaucher disease.

Chronic antigenic stimulation by the abnormal lipid storage has been postulated to be the mechanism underlying anecdotal reports of monoclonal and polyclonal gammopathies as well as an increased incidence of multiple myeloma in patients with Gaucher disease of all ages. With the advent of specific enzyme therapy, it has been possible to ascertain whether signs and symptoms associated with Gaucher disease are true features of the disorder by virtue of their responsiveness to treatment. The purpose of this study was to assess the incidence of polyclonal and monoclonal gammopathies in a large cohort of patients and the effect of enzyme treatment. All adult patients whose records of immunoglobulin levels were available at presentation or at the advent of enzyme replacement therapy (ERT), and who had been followed for 2 years or receiving ERT for at least 2 years, respectively, and for whom there were also immunoglobulin levels at their most recent follow-up, were included in the study. The incidence of polyclonal gammopathies ranged between 14% and 25% among treated and untreated patients. There were statistically significant percentage decreases per year of enzyme therapy in polyclonal but not monoclonal (1% of all patients) gammopathies. Among enzyme-treated patients, there was no statistically significant difference among patients with regard to spleen status or relative to other parameters of disease severity, hepatitis status, age or gender. This study represents the largest database of gammopathies among patients with Gaucher disease from a large referral clinic. Because there was no correlation of abnormal immunoglobulin levels with disease severity, etiology may not be related to lipid accumulation per se but perhaps reflects a secondary, enzyme-sensitive process, whereas monoclonal gammopathies remain unaffected.

Adolescent↗

PubMedDate not supplied

Incidence of malignancies among patients with type I Gaucher disease from a single referral clinic.

BACKGROUND: It has been implied that the incidence of malignant disorders is increased in patients with non-neuronopathic (type I) Gaucher disease. The purpose of the study was to ascertain numbers of cancers in type I Gaucher disease since this is of considerable concern to patients and physicians. METHODS: Records of 505 patients with type I Gaucher disease seen at a large referral clinic since 1990 were culled in December 2004 to ascertain diagnosis of a cancer identified during follow-up. Age-matched data from the Israeli National Cancer Registry (INCR) database were used for comparison. FINDINGS: Patients diagnosed with cancer before 1990 were not included. Of the remaining 500 patients, 227 (45.4%) were male, mean age=38.7 years; and 273 (54.6%) were female, mean age=37.0 years (SD=21.0 years for both). Twenty patients (4.0%) had developed a cancer through December 31, 2003: 6 were male and 14 were female. The most common were three cases each of lymphoma and myelodysplastic syndrome and two cases of multiple myeloma. There was no statistically significant excess of cancer rate among patients relative to age-matched rates reported in national Jewish Israeli and Ashkenazi Jewish Israeli registry records. CONCLUSIONS: There appears to be no excess risk for hematological or other cancers among patients with type I Gaucher disease relative to the overall Jewish population matched for age. This study confirms recent international studies of patients with Gaucher disease for no excess risk for all cancers but multiple myeloma where these latter studies implicate a significantly higher incidence.

Adolescent↗

PubMedDate not supplied

The 1604A (R496H) mutation in Gaucher disease: genotype/phenotype correlation.

Gaucher disease is the most common sphingolipid storage disease but genotype only broadly predicts phenotype. The 1604G-->A (1604A;R496H) mutation has been described as having a low incidence among Ashkenazi Jews. The purpose of this study was to ascertain phenotypic expression and prevalence of this mutation among patients with Gaucher disease and among healthy Ashkenazi Jews. Patients in two Gaucher clinics (in the United States and Israel) and from an international Gaucher registry were assessed for frequency and phenotype expression; 200 healthy Ashkenazi Jews were screened as well. Molecular analysis was performed by standard methods. In the Gaucher clinic with mostly Jewish patients, the gene frequency was 1.68% compared with 0.38% in the international registry with mostly non-Jewish patients. Among Ashkenazi Jewish controls, no alleles with 1604A were identified. There was a marked overrepresentation of severe alleles in patients carrying the 1604A mutation, suggesting that many patients who are compound heterozygotes for 1604A are not diagnosed as having Gaucher disease because their disease is presumably so mild as to evade detection. In view of its rarity and mild expression, the inclusion of the 1604A mutation in the standard kit for screening for Gaucher disease is unnecessary.

Adolescent↗