Recommendations for diagnosis, evaluation, and monitoring of patients with Gaucher disease.
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Absorptiometry, Photon↗
Biomedical subjects
I Hadas-Halpern
Publications and source records attributed to I Hadas-Halpern.
Is there a correlation between degree of splenomegaly, symptoms and hypersplenism? A study of 218 patients with Gaucher disease.
Despite the prevalence of splenomegaly as a sign in many disorders, there have been no studies that correlate the degree of organomegaly with the symptoms generally ascribed to splenic enlargement. The degree of splenomegaly was compared with five overt symptoms of mechanical displacement, i.e. chronic abdominal pain, abdominal discomfort, early satiety, pain while lying on the side, or attacks of acute (colicky) left upper quadrant pains. We have also employed splenomegaly as seen in Gaucher disease as a paradigm to determine whether there is a correlation between the degree of splenomegaly and the parameters of hypersplenism. Although there was a statistically significant correlation between degree of splenomegaly and blood counts, this proved to be clinically negligible. Surprisingly, there was also no correlation between degree of splenomegaly and any of symptoms investigated.
Abdominal Pain↗
Spontaneous intramural hematoma of the esophagus.
Spontaneous intramural hematoma of the esophagus (SIHE) is a rare condition, usually presenting with severe acute chest pain. Vomiting, dysphagia, odynophagia, and hematemesis may appear later. We herein report a case of this disease in a patient treated with low doses of aspirin, and review the literature for possible etiologies for this condition. In addition, we compare the utility of the various diagnostic modalities in this uncommon condition.
Aged↗
Sonographic diagnosis of ureteral tumors.
We present our experience with transabdominal ultrasonographic diagnosis of ureteral tumors. During the years 1989 to 1998, 16 patients were diagnosed as having ureteral tumors. These patients were referred for sonographic examination for evaluation of hematuria (seven patients) or flank pain (four patients) or for follow-up screening in patients who were asymptomatic but at high risk for transitional cell carcinoma because of known past bladder tumor (five patients). Ten of these patients underwent intravenous urography examination, three patients had retrograde pyelography, and 11 patients underwent CT scanning. Ultrasonography revealed the ureteral tumors in all 16 patients, which appeared as hypoechoic intraluminal soft tissue. Three tumors were localized in the upper ureter, four in the middle ureter, and nine in the distal ureter. The degree of ureterohydronephrosis was minimal (two cases), mild (five cases), moderate (eight cases), or severe (one case). Eleven tumors caused local widening of the ureteral diameter. On intravenous urography, four patients had a nonfunctioning kidney, three patients had unexplained ureterohydronephrosis, and three patients showed ureteral filling defects, of which only two had irregular contours. On retrograde pyelography, two patients had filling defects (one of which with smooth margins), and one had a truncated ureter. On CT the tumor was clearly demonstrated in only seven patients. We found that ultrasonography can be a useful diagnostic tool in the workup of ureteral tumors.
Abdominal Pain↗
Echocardiographic assessment of pulmonary hypertension in Gaucher's disease.
BACKGROUND: Enzyme therapy has been shown to decrease the signs and symptoms of Gaucher's disease. A few patients, however, develop pulmonary hypertension on such treatment. We investigated the frequency of pulmonary hypertension in Gaucher's disease. METHODS: We studied 134 adults with type 1 Gaucher's disease, including 73 patients on enzyme replacement, with echocardiography. We measured tricuspid incompetence (TI) with continuous-wave doppler. Pulmonary hypertension was indicated by a TI gradient of more than 30 mm Hg. FINDINGS: Nine (7%) patients had pulmonary hypertension: all were treated and six had undergone splenectomy. Chest radiographs confirmed the presence of pulmonary hypertension in these patients as well as in most patients with TI gradients of 25-29 mm Hg. INTERPRETATION: The confounding effects of disease severity and splenectomy in many treated patients precluded definitive conclusion of cause and effect. Nonetheless, we found an unexpectedly high rate of pulmonary hypertension and recommended routine echocardiographic monitoring of all treated and untreated patients with type 1 Gaucher's disease. We also suggest consideration of treatment withdrawal if the TI gradient progresses to more than 30 mm Hg.
Adult↗
Asymptomatic Gaucher disease implications for large-scale screening.
Gaucher disease, the most prevalent genetic disorder among Ashkenazi Jews, is characterized by significant phenotypic heterogeneity. Because seven mutations account for more than 96% of the disease alleles in this population, large-scale screening is feasible, and genotyping is commercially available. To date, only 400 Gaucher patients have been diagnosed in Israel, although 2,500 patients are predicted by gene frequency; hence, there is the probability that those uncovered by population screening will prove to be very mild or asymptomatic since these patients have generally escaped medical attention until now. We studied objective and subjective aspects in 68 asymptomatic/very mild patients, followed for a mean of 2.6 years, to assess the implications of identifying many more such patients if large-scale screening were to be implemented. We found there were no medically significant changes in disease severity during follow-up. The patients' subjective reports of their general health status were similar to those of normal subjects, and there were no significant changes in quality of life during follow-up. Our findings suggest that asymptomatic/mild Gaucher patients do not require frequent monitoring; there is no justification for "prophylactic" enzyme therapy in this group, and, hence, no rationale for large-scale screening in the Ashkenazi population. Furthermore, one needs to be concerned with the adverse effects of labeling large numbers of asymptomatic individuals as affected because of the potential for stigmatization and discrimination.
Adolescent↗
Low-dose low-frequency imiglucerase as a starting regimen of enzyme replacement therapy for patients with type I Gaucher disease.
The issue of the interplay of optimal dosage and frequency regimens for enzyme replacement therapy in type I Gaucher disease has been a source of controversy during the 7 years since the introduction of the placenta-derived enzymatic preparation in 1991. We present the results of treatment with the human recombinant form of the enzyme in 28 type I Gaucher patients, who have been treated for 6 to 24 months. As long as cost is an important factor in the management of patients with Gaucher disease, low-dose low-frequency imiglucerase promises satisfactory clinical improvement without compromising quality of life.
Adolescent↗
Abdominal ultrasound findings mimicking hematological malignancies in a study of 218 Gaucher patients.
Gaucher disease, the most prevalent sphingolipidosis, generally presents with splenomegaly, anemia, and thrombocytopenia. Hence, hematologists are often the specialists involved in diagnosis and management of these patients. We present ultrasonographic characteristics in a cohort of 218 consecutive Gaucher patients evaluated in our clinic during the past 5 years. Our data emphasize the high prevalence of lesions mimicking hematological malignancies in Gaucher disease. One fifth of 184 non-splenectomized patients had intra-splenic lesions, 6% of all patients had similar lesions in the liver, and 32% of 34 splenectomized patients (but none of the other patients) had marked retroperitoneal or peri-portal lymphadenopathy. The presence of splenic lesions correlated with age and splenic size, but not with extent of bone involvement or genotype. Interestingly, they were not affected by reduction in splenomegaly following enzyme replacement therapy. The importance of these findings is to include Gaucher disease in the differential diagnosis of splenic or hepatic lesions, especially in Ashkenazi Jews. Conversely, they are relevant for follow-up of all Gaucher patients, including asymptomatic individuals, because of the reported increased incidence of hematological malignancies in Gaucher disease.
Adolescent↗
Accuracy of ultrasonography in assessing spleen and liver size in patients with Gaucher disease: comparison to computed tomographic measurements.
A comparison was made between volume measurements of spleen and liver by ultrasonography and by computed tomography, the two most common modes of assessment of organ size in patients with Gaucher disease, who require frequent follow-up measurements. The two measurements showed a high degree of correlation within a broad range for both spleen and liver volumes. An algorithm for conversion of one measurement to the other was derived for both spleen and liver.
Adolescent↗
Effect of low-dose enzyme replacement therapy on bones in Gaucher disease patients with severe skeletal involvement.
Gaucher disease, the most common glycolipid storage disorder, is characterized by hepatosplenomegaly and skeletal involvement. Enzyme replacement therapy in both the high- and low-dose regimens has been shown to be effective in reducing the organomegaly and improving the hematological parameters of symptomatic patients with type I disease. Herein we report subjective and objective responses of bone-related complications after 2 to 4 years of low-dose enzyme replacement therapy in 14 adult type I patients with severe skeletal involvement pre-treatment. We discuss our results relative to those reported in patients on the high-dose regimen, as well as with reference to a single patient who developed new avascular necrosis despite objective improvement in radiological studies.
Adolescent↗
Pulmonary function abnormalities in type I Gaucher disease.
The purpose of this study was to determine the prevalence of pulmonary function and radiographic abnormalities among patients with type I Gaucher's disease, and to analyse the relationship between the pulmonary involvement and genotype and clinical severity score. All patients attending the Gaucher clinic at the Shaare Zedek Medical Center, Jerusalem, Israel, during the years 1992-1993 were prospectively evaluated. Each patient had pulmonary function tests, chest radiography, clinical assessment in terms of degree of organ involvement, and genotype analysis. Of the 95 patients included in the study (mean +/- SD age 29 +/- 15 yrs), 68% had some pulmonary function abnormalities, most commonly a reduced FRC and transfer coefficient for carbon monoxide (Kco), found in 45% and in 42% of the patients respectively. Total lung capacity (TLC) was reduced in 22% of the patients and forced expiratory flows in approximately one third of the patients. Signs of airtrapping (elevated residual volume (RV) or RV/TLC) were seen in 18% of the patients. Males had a higher incidence of reduced expiratory flow than females, (forced expiratory volume in one second (FEV1) was reduced in 36% of males vs 5% of females). Chest radiographic abnormalities were found in 17% of the patients, although only 4% had severe changes. Patients with abnormal pulmonary function had a significantly higher severity score index than those with normal pulmonary function tests. There was no association between abnormal pulmonary function and genotype or age. In conclusion, abnormal pulmonary function is common among type I Gaucher patients. Pulmonary function tests show airways obstruction, with reduced expiratory flows, reduction in lung volumes and alveolar-capillary diffusion abnormality. The rate of progression and the clinical significance need to be determined.
Adolescent↗
Gaucher's disease variant characterised by progressive calcification of heart valves and unique genotype.
Gaucher's disease is the most prevalent sphingolipid storage disease, characterised by substantial genetic and phenotypic variability. Cardiac manifestations are rare. We report 12 Arab Gaucher's disease patients, 2-20 years of age, who presented with oculomotor apraxia but only slight classic signs of the disease. All but the youngest had calcifications of the aortic or mitral valves or both. All these patients were homozygous for the rare point mutation D409H (1342C). Valvular calcifications increased with age and showed progression during 2 years of follow-up. Two of the oldest patients underwent aortic valve replacement, and one sibling had died suddenly at age 16, before this study, Corneal opacities were another common feature. The potentially fatal course of this Gaucher's disease variant, and the availability of a reliable PCR-based method for heterozygote detection, mean that population screening and genetic counselling in the geographic area at risk are important. Affected individuals should be closely monitored by echocardiography to gauge the need for valve replacement. The potential of enzyme replacement to prevent these cardiac complications cannot be ascertained at present, because of the high cost of therapy.
Adolescent↗
Replacement therapy with imiglucerase for type 1 Gaucher's disease.
Gaucher's disease, the most common sphingolipidosis, is caused by deficiency of the lysosomal enzyme glucocerebrosidase. Therapy with alglucerase (the placental enzyme) is safe and effective at various dosing regimens. We report the use of low-dose imiglucerase (the recombinant enzyme) at two dosing schedules: 15 u/kg once fortnightly or 2.5 u/kg thrice weekly. Mean reductions in spleen and liver volumes achieved (in all ten patients) by imiglucerase at 12 months were 36.4% and 14.5%, respectively; mean increase in haemoglobin and platelet counts were 13.4% and 25.7%. There were no serious side-effects. No significant differences were observed between the two schedules. Low-dose low-frequency imiglucerase may be an alternative cost-effective approach with satisfactory clinical response and uncompromised quality of life.
Adolescent↗
Sclerosing haemangioma of lung mimicking carcinoma diagnosed by fine needle aspiration (FNA) cytology.
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Adenocarcinoma, Clear Cell↗
Richter's hernia strangulated in a spigelian hernia: ultrasonic diagnosis.
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Aged↗
Low-dose enzyme replacement therapy for Gaucher's disease: effects of age, sex, genotype, and clinical features on response to treatment.
Although alglucerase therapy has become the treatment of choice for symptomatic patients with Gaucher's disease, the low-dose/high-frequency regimen introduced as a means to reduce the high cost of treatment has raised major controversy. We evaluated the efficacy and safety of low-dose alglucerase in 29 patients with Gaucher's disease who completed 6 to 28 months of therapy. All received intravenous alglucerase at a monthly dose of 30 units/kg, given usually in equal doses 3 times a week. All patients responded well to treatment. The hematological improvement and the reduction in organomegaly were satisfactory. No correlation was found between age, sex, genotype, previous splenectomy, or severity score index and the response to treatment. Patients with a greater degree of hepatomegaly tended to have a more pronounced decrease in liver size, although this reduction did not reach statistical significance. We confirmed that a low-dose/high-frequency regimen of alglucerase was as effective as a high-dose/low-frequency protocol in the treatment of Gaucher's disease, even in the severely ill. Whenever cost is an issue, we recommend using this low-dose regimen.
Adolescent↗
The changing clinical spectrum of liver abscess: the Jerusalem experience.
A retrospective study was conducted of all 31 patients with liver abscess admitted to Shaare Zedek Medical Center between 1979, the year computed tomographic scan and ultrasound were introduced, and 1992. Fever and abdominal pain were the most common symptoms. Duration of symptoms was short: 81% of patients had symptoms for < or = 5 days and none had symptoms for more than 3 weeks. Amoebic abscess was found in one patient only, the remainder were pyogenic. Biliary tract pathology remains the most common cause of liver abscess (39%). The diagnosis was made by ultrasound in 22/31 (71%) and by computed tomographic scan in 9/31 (29%) of patients. Treatment consisted of intravenous antibiotics and percutaneous drainage under ultrasound guidance in 24/31 patients (77%). Four patients died (13%), three of whom had underlying malignancies. Clinical features were compared with those from a similar series of 36 cases with liver abscess reported from Jerusalem predating ultrasound and computed tomographic scan (1967-1977). Several major changes have occurred. First, the relative incidence of amoebic abscess has dramatically decreased. Second, ultrasound and computed tomographic scan have facilitated earlier diagnosis and percutaneous drainage, contributing to improved survival and lower morbidity.
Adolescent↗
[Fine needle aspiration of thoracic lesions].
Recent radiologic techniques can detect masses as small as 1 cm in diameter. In combination with fine needle aspiration (FNA), quick and reliable diagnosis of thoracic lesions is now possible and the methods are now accepted worldwide. Several studies have shown that FNA is more sensitive than conventional cytology (including sputum smears and bronchoscopic brushes and washes). Although complications and risks are associated with FNA, they are minimal compared to those of thoracotomy. Between 1976-1990, FNA was performed on 107 patients with pulmonary lesions. In 97 of them, the aspirates were positive for malignancy in 76%, in 7% there was a suspicion of malignancy, and 15% were negative. Diagnostic accuracy was similar for lesions 1 cm or 3 cm in diameter.
Biopsy, Needle↗