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Irith Hadas-Halpern

Publications and source records attributed to Irith Hadas-Halpern.

15 recordsLinked to original sources
PubMed2006

Iliopsoas haematoma in Gaucher disease.

Extrapelvis or retroperitoneal haemorrhage has long been appreciated as having many causes and considerable variability in subsequent morbidity; however, to date only two cases have been reported in patients with Gaucher disease, the most common lysosomal storage disorder. It had been our assumption that these cases were unique and a consequence of severe disease in patients who had not been treated with enzyme (or other disease-specific) therapy. Herein we present three more cases (as well as our first patient), which allow one to make some generalizations. Ultrasound was used in one centre and computed tomography in the second centre to make the definitive diagnosis. The trigger for the bleeding in all cases was muscle strain after activity. All patients were young with massive hepatosplenomegaly, anaemia, thrombocytopenia, and bone pain with skeletal involvement; the last was the most obvious commonality among these patients. Differential diagnosis is complicated by exquisite groin pain that is common to both Gaucher disease and extrapelvis haemorrhage, but not necessarily.

Adolescent↗
PubMed2005

A comprehensive assessment of renal function in patients with Gaucher disease.

BACKGROUND: Gaucher disease (GD) is caused by deficiency of acid beta-glucocerebrosidase and is the most common lysosomal storage disease. Patients may have massive hepatosplenomegaly, severe bone disease, and, occasionally, pulmonary or neurological involvement. Although other storage diseases, such as Fabry disease, frequently affect the kidneys, reports of renal abnormalities in patients with GD are limited to case reports. Our aim was to perform a comprehensive evaluation of renal function in patients with GD. METHODS: Evaluation was performed at routine clinic visits and included blood pressure recording and renal ultrasound. Serum chemistries, urinalysis, urine electrolytes, total protein, and tubular proteinuria were assessed, and estimated glomerular filtration rate (GFR) was calculated. RESULTS: One hundred sixty-one patients underwent evaluation, including 26 children. GFR was significantly greater in patients with GD than in age- and sex-matched healthy controls (P = 0.01 in men, P < 0.001 in women, P = 0.003 in children). Subgroups of patients with markers of more severe disease had a greater GFR than other patients. No patient had decreased renal function. Significant proteinuria was found only in patients with such comorbidities as diabetes mellitus or multiple myeloma. No evidence of renal tubular abnormalities was found, and kidney sonographic appearance and size were normal. CONCLUSION: Despite the multiorgan nature of the disease, a systematic evaluation did not find renal abnormalities in patients with GD. Glomerular hyperfiltration was observed in a proportion of patients, particularly those with markers of more severe disease. This phenomenon does not seem to be associated with a subsequent decline in renal function.

Adolescent↗
PubMed2005

Menetrier's disease presenting as an acute protein-losing gastroenteropathy in a 27-year-old man with Gaucher disease.

OBJECTIVES: To describe a unique case of a young man with Gaucher disease who was diagnosed with Menetrier's disease. BACKGROUND: After an acute episode of severe gastritis, the patient developed hypoalbuminemia and protein-losing gastroenteropathy, and became unwell. STUDY: Endoscopy revealed an abnormal stomach, with rigid, thickened folds covered with viscous greyish exudates. Superficial biopsies revealed foveolar hyperplasia, acute and severe gastritis with massive inflammatory infiltrate of neutrophils in the lamina propria with pit abscess formation. Tissue cultures for Helicobacter pylori were negative. RESULTS: Snare deep particle biopsy revealed the typical features of Menetrier's disease. Enzyme replacement therapy for Gaucher disease was started. CONCLUSION: This case poses a dilemma because the patient improved spontaneously, and as such is dissimilar to other adults who develop Menetrier's disease because of an infection; it is hoped that he may also not be at risk of the potential malignancies that are correlated with adult Menetrier's disease. The value of enzyme treatment is considered.

Acute Disease↗
PubMed2004

Orthopedic considerations in Gaucher disease since the advent of enzyme replacement therapy.

Gaucher disease, the most prevalent lysosomal storage disorder, is characterized by hepatosplenomegaly, hypersplenism, and rarely, neurological involvement. The most variable symptoms relate to skeletal disease, and both onset and progression are difficult to predict on the basis of genotype. This review describes findings from a large referral clinic (> 500 patients) and from the literature in the decade since the advent of specific enzyme replacement therapy. Such therapy is effective in reducing visceral and hematological involvement, but its greatest advantage as regards the skeleton is prevention of irreversible damage. Avascular necrosis of the joints-particularly the hips but also the knees and shoulders-and pathological fractures of the long bones including the ribs, as well as episodic "crises' of bone pain in children and young adults, are common manifestations. Various imaging modalities should be performed at baseline for life-long monitoring, and then as required because of specific complaints. Surgical interventions such as joint arthroplasties are important adjuvant treatments in this population; presurgical hematological profiling plus antibiotic cover and postoperative pain control are equally critical. Opportunities for orthopedic consultations with senior surgeons are not abused by our patients. These reflect disease-related morbidity, with greater numbers of requests being made by patients requiring enzyme therapy, who by definition have more severe disease characteristics.

Adolescent↗
PubMed2004

Increased prevalence of cholelithiasis in Gaucher disease: association with splenectomy but not with gilbert syndrome.

GOALS: The purpose of this study is to ascertain the incidence of gallstones among adult patients with type 1 Gaucher disease and whether the presence of the UDPGT1 polymorphism (Gilbert syndrome), increases the incidence of gallstones. BACKGROUND: Cholelithiasis was been observed among patients with type I Gaucher disease with variable frequency. Too, studies have addressed the possibility of an association between Gilbert syndrome and formation of bilirubinate gallstones in hereditary spherocytosis wherein, like Gaucher disease, there is hemolysis of blood cell membranes. METHODS: Medical records of all adult patients with type 1 disease in a referral clinic were reviewed for evidence of gallstones or cholecystectomy. Blood samples were collected for molecular analysis for Gilbert syndrome. RESULTS: Of 323 adult patients, 82 patients (25.4%), 54 women (65.9%) and 28 men (34.1%), had evidence of gallbladder disease (P < 0.001 relative to normal white controls). There was a statistically significant increase (P < 0.001) for all groups above the ages of 20 years other than for men aged 40 to 49 years. There was a statistically significant association between splenectomy and both cholelithiasis (P = 0.022) and Gilbert syndrome (P = 0.002). CONCLUSIONS: This study highlights an increase incidence of cholelithiasis but not Gilbert syndrome among patients with Gaucher disease. Storage of glycolipid per se or an immune reaction to storage, may explain these findings.

Adult↗
PubMed2003

Percutaneous cholecystostomy in the management of acute cholecystitis.

BACKGROUND: The mainstay of therapy for acute cholecystitis is cholecystectomy, which has a mortality of 14-30% in high risk patients. An alternative approach in patients suffering from acute cholecystitis with contraindications to emergency surgery is percutaneous cholecystostomy. OBJECTIVE: To evaluate the efficacy and safety of percutaneous cholecystostomy as the initial treatment of acute cholecystitis in high risk patients. METHODS: Eighty consecutive patients (42 men, 38 women) underwent ultrasound-guided percutaneous cholecystostomy over a 5 year period. Sixty-five patients suffered from acute calculous cholecystitis, 4 patients had acalculous cholecystitis, and 11 patients had sepsis of unknown origin. RESULTS: Sixty-eight patients improved after the percutaneous gallbladder drainage, 10 patients died from co-morbid disease and 2 patients died from biliary peritonitis. During a 1 year follow-up, 32 of the patients underwent interval cholecystectomy, 4 additional patients died from a co-morbid disease, 18 patients did not suffer from any gallbladder symptoms, and 14 were lost to follow-up. CONCLUSIONS: Percutaneous cholecystostomy is an effective contribution to the treatment of acute cholecystitis in high risk patients.

Acute Disease↗
PubMed2002

Repeat abdominal ultrasound evaluation of 100 patients with type I Gaucher disease treated with enzyme replacement therapy for up to 7 years.

With the advent of enzyme replacement therapy for Gaucher disease, there was a need to assess response to treatment repeatedly over relatively short periods of time; hence abdominal ultrasound was used in our referral clinic because it was convenient, safe and inexpensive. In 100 treated patients monitored for 2-7 years, nearly all had reduction in hepatosplenomegaly. The per cent reduction was more dramatic in patients who started treatment when older than 16 years. This effect may be explained by a correlation between per cent reduction and degree of baseline organomegaly. Because children often initiate therapy sufficiently early to preclude developing massive organomegaly, the observed per cent reduction is commensurately less. For all patients treated for more than five years, plateau-ing in response was seen after the first three years of treatment. This study permits us to reconsider less frequent evaluations of organ volumes. Our findings also underscore the efficacy of enzyme replacement, but raise the question of the need for dose reduction as nearly normal organ volumes are achieved.

Abdomen↗
PubMed2002

Type I Gaucher disease in children with and without enzyme therapy.

This retrospective study describes the course of 56 children with non-neuronopathic Gaucher disease who presented at <16 years and were followed at 6- to 12-month intervals for 3-9 years. Massive splenomegaly and height retardation marked those who required treatment. Enzyme replacement significantly increased hemoglobin levels; platelet counts were divergent at presentation and follow-up, regardless of therapy. Among treated patients there was a significant reduction in liver and spleen index volumes, and a significant increase in height z-scores. None of the children required splenectomy or developed lung involvement. Many patients diagnosed due to large-scale screening were very mildly affected and remain untreated.

Body Height↗
PubMed2002

Tc-99m sestamibi bone marrow scintigraphy in Gaucher disease.

PURPOSE: No imaging technique has been found to be adequate to assess the severity and extent of bone involvement in patients with Gaucher disease. Marrow involvement, as determined by Tc-99m sulfur colloid, correlated well with the clinical and radiologic changes of the skeleton, but a normal pattern was found in the early stages of the disease. Subsequently, Tc-99m sestamibi (MIBI) has been suggested for direct visualization of glycolipid deposits in the bone marrow. This study was initiated as a pilot using MIBI to detect various forms of bone disease in patients with Gaucher disease of varying severity. MATERIALS AND METHODS: Eleven patients (9 men; median age, 39.9; age range, 21 to 61 years) were evaluated. The clinical severity of disease was scored at presentation, and four patients with moderate to severe disease were treated with enzyme replacement therapy. Each patient underwent a radiographic skeletal survey, bone densitometry, and MIBI scintigraphy. The scan included static images of the lower limbs, with a whole-body scan acquired between the early and late acquisition. Tracer uptake in the bone marrow was graded and correlated with clinical and objective variables. RESULTS: All but one patient had increased MIBI uptake in the bone marrow. No correlation was noted between MIBI uptake and severity score, radiographic changes, densitometry z score, or treatment status. CONCLUSIONS: MIBI scanning is a sensitive technique for detecting bone marrow deposits in Gaucher disease, but it is inadequate for early identification of patients at high risk for skeletal complications or for the follow-up of patients treated with enzyme replacement.

Adult↗
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↗
PubMed2002

Multiple hypoechoic hepatic lesions in a patient with Gaucher disease.

The most common symptoms of Gaucher disease include hepatosplenomegaly and anemia and thrombocytopenia due to hypersplenism. We describe the case of a patient with Gaucher disease who had cachexia, massive hepatomegaly, and multiple focal hepatic lesions. The clinical and radiologic findings suggested malignancy. A biopsy specimen was taken from a hepatic lesion and revealed infiltration by Gaucher cells. We discuss our findings in light of the putative increased incidence of hematologic malignancies in patients with Gaucher disease.

Adult↗
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↗