Derralynn Hughes

Publications (19)82.93 Total impact

• Article: Retinal thinning in Gaucher disease patients and carriers: Results of a pilot study.

  Alisdair McNeill, Gloria Roberti, Gerassimos Lascaratos, Derralynn Hughes, Atul Mehta, David F Garway-Heath, Anthony H V Schapira
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  ABSTRACT: Both Gaucher disease patients and heterozygous glucocerebrosidase mutation carriers are at increased risk of Parkinson's disease. Retinal thinning has been reported in early Parkinson's disease. Here we used optical coherence tomography to demonstrate thinning of the retinal ganglion cell layer in Gaucher disease patients and carriers who manifest clinical markers of potential early neurodegeneration. Optical coherence tomography may help identify Gaucher disease patients and carriers at increased risk of developing Parkinson's disease.
  Molecular Genetics and Metabolism 04/2013; · 3.19 Impact Factor
• Article: The glucocerobrosidase E326K variant predisposes to Parkinson's disease, but does not cause Gaucher's disease.

  Raquel Duran, Niccolo E Mencacci, Aikaterini V Angeli, Maryam Shoai, Emma Deas, Henry Houlden, Atul Mehta, Derralynn Hughes, Timothy M Cox, Patrick Deegan, Anthony H Schapira, Andrew J Lees, Patricia Limousin, Paul R Jarman, Kailash P Bhatia, Nicholas W Wood, John Hardy, Tom Foltynie
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  ABSTRACT: BACKGROUND: Heterozygous loss-of-function mutations in the acid beta-glucocerebrosidase (GBA1) gene, responsible for the recessive lysosomal storage disorder, Gaucher's disease (GD), are the strongest known risk factor for Parkinson's disease (PD). Our aim was to assess the contribution of GBA1 mutations in a series of early-onset PD. METHODS: One hundred and eighty-five PD patients (with an onset age of ≤50) and 283 age-matched controls were screened for GBA1 mutations by Sanger sequencing. RESULTS: We show that the frequency of GBA1 mutations is much higher in this patient series than in typical late-onset patient cohorts. Furthermore, our results reveal that the most prevalent PD-associated GBA1 mutation is E326K, a variant that does not, when homozygous, cause GD. CONCLUSIONS: Our results confirm recent reports that the mutation, E326K, predisposes to PD and suggest that, in addition to reduced GBA1 activity, other molecular mechanisms may contribute to the development of the disease. © 2012 Movement Disorder Society.
  Movement Disorders 12/2012; · 4.51 Impact Factor
• Article: Phenotypical characterization of α-galactosidase A gene mutations identified in a large Fabry disease screening program in stroke in the young.

  Isabel De Brabander, Laetitia Yperzeele, Chantal Ceuterick-De Groote, Raf Brouns, Robert Baker, Shibeshih Belachew, Jean Delbecq, Gilles De Keulenaer, Sophie Dethy, François Eyskens, [......], Derralynn Hughes, Sandrine Jeangette, Dirk Nuytten, Patricia Redondo, Bernard Sadzot, Christian Sindic, Rishi Sheorajpanday, Vincent Thijs, Christine Van Broeckhoven, Peter P De Deyn
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  ABSTRACT: OBJECTIVE: In the Belgian Fabry Study (BeFaS), the prevalence of Fabry disease was assessed in 1000 young patients presenting with stroke, unexplained white matter lesions or vertebrobasilar dolichoectasia. The results of the BeFaS suggested that Fabry disease may play a role in up to 1% of young patients presenting with cerebrovascular disease. However, the clinical relevance was unclear in all cases. We report on detailed phenotyping in subjects identified with α-galactosidase A (α-Gal A) enzyme deficiency or GLA mutations identified in the BeFaS (n=10), and on the results of family screening in this population. METHODS: Family screening was performed to identify additional mutation carriers. Biochemical and/or clinical evaluation of all subjects (BeFaS index patients and relatives carrying a GLA mutation) was performed. RESULTS: Genetic family screening revealed 18 additional GLA mutation carriers. Bloodspot α-Gal A enzyme activity was normal in all GLA mutation carriers, even in 2 males with the p.A143T mutation. Plasma Gb3 and lyso-Gb3 levels were normal in all subjects. Elevated Gb3 in urine was detected in 2 subjects. Some classic clinical signs of Fabry disease, like angiokeratoma or cornea verticillata, could not be detected in our population. Cardiac symptoms of Fabry disease were found in 6 out of 10 p.A143T carriers. No signs of cerebrovascular disease were found in the relatives with a GLA mutation. CONCLUSIONS: We could not identify mutations causing the classical clinical phenotype of Fabry disease in our cerebrovascular disease population. Enzyme activity analysis in bloodspots and plasma may fail to identify late-onset variants of Fabry disease. We recommend genetic testing when an atypical, late-onset variant of Fabry disease is suspected in a male cerebrovascular disease patient. However, this may lead to the identification of non-disease causing or controversial genetic variants.
  Clinical neurology and neurosurgery 12/2012; · 1.30 Impact Factor
• Article: Role of Serum N-Terminal Pro-Brain Natriuretic Peptide Measurement in Diagnosis of Cardiac Involvement in Patients With Anderson-Fabry Disease.

  Caroline J Coats, Valentina Parisi, Monica Ramos, Kalaiarasi Janagarajan, Constantinos O'Mahony, Anne Dawnay, Robin H Lachmann, Elaine Murphy, Atul Mehta, Derralynn Hughes, Perry M Elliott
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  ABSTRACT: Enzyme replacement therapy has the potential to delay or reverse adverse cardiac remodeling in Anderson-Fabry disease (AFD); however, the current indications for enzyme replacement therapy rely on detecting relatively advanced features of the disease. We aimed to determine the relation between the serum N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration and cardiac abnormalities in patients with AFD. We hypothesized that it might help to detect early disease. NT-proBNP was measured under at rest conditions in 117 patients with AFD (age 48 ± 15 years, 46.2% men). All patients underwent clinical evaluation with electrocardiography and echocardiography. The median NT-proBNP concentration was 24 pmol/L (range <5 to 6,059). Of the 117 patients, 67 (57%) had elevated, age-corrected, NT-proBNP levels. In the 56 patients (48%) with normal echocardiographic findings, the NT-proBNP levels were greater than the age-predicted cutoffs in 10 of 25 patients with abnormal electrocardiographic findings and 3 of 31 patients with normal electrocardiographic findings (p <0.05). On multiple regression analysis, age, creatinine, left atrial volume index, E/Ea, and the presence of abnormal electrocardiographic findings were independently associated with log NT-proBNP (R(2) = 0.67, p <0.05). In conclusion, NT-proBNP concentrations were elevated in patients with AFD and early cardiac involvement, suggesting its measurement could assist in decisions regarding the timing of enzyme replacement therapy.
  The American journal of cardiology 10/2012; · 3.58 Impact Factor
• Article: Novel pathogenic mutations in the glucocerebrosidase locus.

  Raquel Duran, Alisdair McNeill, Atul Mehta, Derralyn Hughes, Timothy Cox, Patrick Deegan, Anthony H V Schapira, John Hardy
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  ABSTRACT: To determine the frequency of mutations responsible for Gaucher's disease, we systematically sequenced the GBA1 gene as part of a molecular characterization of 73 adult patients in the United Kingdom. Five hitherto unknown pathogenic variants were identified, one of which is a splice site change; the others are novel missense mutations. Given that GBA1 gene mutations are an important risk factor for the development of Parkinson's disease, we contend that a complete analysis and molecular characterization of both the known and novel GBA1 variants will be needed before the biochemical processes underlying this genetic association can be fully understood.
  Molecular Genetics and Metabolism 05/2012; 106(4):495-7. · 3.19 Impact Factor
• Article: The cognitive profile of type 1 Gaucher disease patients.

  Marieke Biegstraaten, Keith A Wesnes, Cécile Luzy, Milan Petakov, Mirando Mrsic, Claus Niederau, Pilar Giraldo, Derralynn Hughes, Atul Mehta, Karl-Eugen Mengel, Carla E M Hollak, László Maródi, Ivo N van Schaik
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  ABSTRACT: The absence of neurological symptoms and signs is traditionally considered mandatory for a diagnosis of type 1 Gaucher disease (GD1), but in recent years many reports have emerged on neurological manifestations in GD1 patients. Nevertheless, it has been unclear whether cognitive deficits are part of the disease as well. Cognitive function was assessed in a large cohort of GD1 patients with the use of the CDR system, a set of computerised cognitive tests. Testing was performed at baseline and every 6 months thereafter during a two-year study period. Our patient cohort (84 patients, median age 40 years, median time from diagnosis 15 years) showed mild deficits relative to healthy age-matched subjects on the composite scores: power of attention (Z-score (mean ± SD) -0.9 ± 1.37) and speed of memory (Z-score (mean ± SD) -1.39 ± 1.49). No decline in cognitive function was seen during the two-year period. Age correlated with the composite scores variability of attention and quality of working memory. Moreover, severely affected patients (Zimran severity score (SSI) ≥ 15) scored more poorly compared to mildly affected patients (SSI ≤ 5) on the composite measure power of attention, reflecting the ability to concentrate. GD1 patients exhibit mild deficits in power of attention and speed of memory, reflecting a decreased ability to focus attention and process information, together with a slowing in the speed of retrieval of items from memory. The clinical relevance of these findings is uncertain.
  Journal of Inherited Metabolic Disease 02/2012; 35(6):1093-9. · 3.58 Impact Factor
• Article: Incidence and predictors of anti-bradycardia pacing in patients with Anderson-Fabry disease.

  Constantinos O'Mahony, Caroline Coats, Monserrat Cardona, Alfredo Garcia, Margherita Calcagnino, Elaine Murphy, Robin Lachmann, Atul Mehta, Derralynn Hughes, Perry M Elliott
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  ABSTRACT: Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder associated with bradyarrhythmias. We sought to examine the nature of conduction system abnormalities and the indications and determinants of anti-bradycardia pacing in patients with AFD. We studied 204 patients with AFD (49% male, mean age 42 years) in an observational, longitudinal, retrospective cohort study. At baseline, 5 (2.5%) patients had pacemakers for the treatment of bradycardias [4/5 (80%) for atrioventricular disease; 1/5 (20%) for sinus node disease]. PR interval <120 ms was observed in 15 (7%); PR interval >200 ms in 6 (3%); QRS interval >120 ms 18 (9%); left QRS axis deviation in 16 (8%); and right-axis deviation in 2 (1%). Age was an independent determinant of prolonged PR interval, QRS duration and left QRS axis deviation. During follow-up (189 patients; 899 patient-years), 12 (6%) had a device implanted to treat spontaneously occurring bradyarrhythmias [5/12 (42%) for atrioventricular disease; 7/12 (58%) sinus node disease] with 8% 5-year cumulative incidence. Two independent predictors of future anti-bradycardia pacing were identified in a multivariable Cox model: QRS duration [hazard ratio (HR) 1.05, 95% confidence intervals (CI) 1.02-1.09, P= 0.001; receiver operating characteristic (ROC) curve c-statistic 0.726] and PR interval duration (HR 1.03, 95% CI 1.004-1.060, P = 0.023; ROC curve c-statistic 0.548). QRS duration ≥110 ms at baseline had a sensitivity of 64%, specificity of 84%, 49% positive predictive value, and 91% negative predictive value for identifying patients likely to require anti-bradycardia pacing. In patients with AFD increasing age is associated with PR and QRS interval prolongation and left QRS axis deviation. Pacing for atrioventricular and sinus node disease is common and patients with QRS≥110 ms should be closely monitored for bradyarrhythmias.
  Europace 08/2011; 13(12):1781-8. · 1.98 Impact Factor
• Article: Exercise-induced left ventricular outflow tract obstruction in symptomatic patients with Anderson-Fabry disease.

  Margherita Calcagnino, Constantinos O'Mahony, Caroline Coats, Montserrat Cardona, Alfredo Garcia, Kalajarasi Janagarajan, Atul Mehta, Derralynn Hughes, Elaine Murphy, Robin Lachmann, Perry M Elliott
  Journal of the American College of Cardiology 06/2011; 58(1):88-9. · 14.16 Impact Factor
• Article: Osseous manifestations of adult Gaucher disease in the era of enzyme replacement therapy.

  Patrick B Deegan, Elena Pavlova, Jane Tindall, Penelope E Stein, Philip Bearcroft, Atul Mehta, Derralynn Hughes, J Edmund Wraith, Timothy M Cox
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  ABSTRACT: Enzyme replacement therapy (ERT) for Gaucher disease with mannose-terminated glucocerebrosidase has proved its therapeutic position with salutary effects on hematologic abnormalities, visceral infiltration, and quality of life. The frequency of new bone complications is reduced but not eliminated. Established osteonecrosis is beyond salvage. A systematic description of the burden of bone manifestations, persisting despite ERT, should inform future remedial strategies. Thus, we conducted this study to quantify the burden of residual skeletal disease and to explore putative relationships between clinical, radiologic, and biochemical factors and bone sequelae associated with disability.Consecutive adult patients attending 3 referral centers in the United Kingdom were invited to participate. A representative group of 100 patients agreed to a structured interview, clinical examination, radiologic review, and completion of questionnaires. Osteonecrosis was evident in 43%, Erlenmeyer flask deformity in 59%, fragility fracture in 28%, osteomyelitis in 6%, and lytic lesions in 4%. Mobility was impaired in 32% of patients, while 15% experienced significant pain. The EuroQol 5D (EQ5D) quality of life summary measure was reduced and was associated with osteonecrosis and fragility fracture. Eight patients experienced new osteonecrosis after the start of ERT, though the presentation and evolution were often atypical. Nine patients had been treated from childhood and had an excellent outcome. Osteonecrosis was associated with age of presentation and with splenectomy-indeed, we observed a strong temporal association between splenectomy and incidence of osteonecrosis.The biomarkers PARC/CCL18 and chitotriosidase were associated with prevalent osteonecrosis, and, in particular, with osteonecrosis occurring despite treatment. This study documents significant residual skeletal pathology and disability in patients in the mature phase of their treatment in a developed region. The temporal association between splenectomy and osteonecrosis implies causation. The relationship between clinical and biochemical markers and existing bone complications sets the scene for future prospective studies that will focus on management strategies informed by credible assessment of risk.
  Medicine 01/2011; 90(1):52-60. · 4.35 Impact Factor
• Source

  Available from: Carla E Hollak

  Article: Expert opinion on temporary treatment recommendations for Fabry disease during the shortage of enzyme replacement therapy (ERT).

  Gabor E Linthorst, Dominique P Germain, Carla E M Hollak, Derralynn Hughes, Arndt Rolfs, Christoph Wanner, Atul Mehta
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  ABSTRACT: The shortage of enzyme for treatment of Fabry disease has caused anxiety among patients, physicians and governments. Following a request from the European Medicines Agency, consensus was reached on the temporary prioritization of patients for treatment based on disease severity and potential reversibility. Advice on follow-up of patients was agreed upon. This consensus is proposed to support the temporary guidelines issued throughout the period of ERT shortage, which will most likely last until April 2011.
  Molecular Genetics and Metabolism 01/2011; 102(1):99-102. · 3.19 Impact Factor
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  Available from: Francois Eyskens

  Article: Belgian Fabry study: prevalence of Fabry disease in a cohort of 1000 young patients with cerebrovascular disease.

  Raf Brouns, Vincent Thijs, François Eyskens, Marleen Van den Broeck, Shibeshih Belachew, Christine Van Broeckhoven, Patricia Redondo, Dimitri Hemelsoet, Arnaud Fumal, Sandrine Jeangette, Werner Verslegers, Robert Baker, Derralynn Hughes, Peter Paul De Deyn
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  ABSTRACT: Data on the prevalence of Fabry disease in patients with central nervous system pathology are limited and controversial. In this study, we assessed the prevalence of Fabry disease in young patients presenting with cerebrovascular disease in Belgium. In this national, prospective, multicenter study, we screened for Fabry disease in 1000 patients presenting with ischemic stroke, transient ischemic attack, or intracranial hemorrhage; unexplained white matter lesions; or vertebrobasilar dolichoectasia. In male patients, we measured alpha-galactosidase A (alpha-GAL A) activity in dried blood spots. Female patients were screened for mutations by exonic DNA sequencing of the alpha-GAL A gene. alpha-GAL A activity was deficient in 19 men (3.5%), although all had normal alpha-GAL A gene sequences. Enzymatic deficiency was confirmed on repeat assessment in 2 male patients (0.4%). We identified missense mutations in 8 unrelated female patients (1.8%): Asp313Tyr (n=5), Ala143Thr (n=2), and Ser126Gly (n=1). The pathogenicity of the 2 former missense mutations is controversial. Ser126Gly is a novel mutation that can be linked to late-onset Fabry disease. alpha-GAL A deficiency may play a role in up to 1% of young patients presenting with cerebrovascular disease. These findings suggest that atypical variants of Fabry disease with late-onset cerebrovascular disease exist, although the clinical relevance is unclear in all cases.
  Stroke 04/2010; 41(5):863-8. · 5.73 Impact Factor
• Article: Guidelines for the restart of imiglucerase in patients with Gaucher disease: recommendations from the European Working Group on Gaucher disease.

  Carla E M Hollak, Johannes M F G Aerts, Nadia Belmatoug, Bruno Bembi, Olaf Bodamer, Domenica Cappellini, Tanya Collin-Histed, Timothy M Cox, Patrick Deegan, Pilar Giraldo, Derralynn Hughes, Elena Lukina, Jeremy Manuel, Helen Michelakakis, Maja Di Rocco, Ashok Vellodi, Ari Zimran
  Blood Cells Molecules and Diseases 12/2009; 44(2):86-7. · 2.35 Impact Factor
• Article: Miglustat (Zavesca) in type 1 Gaucher disease: 5-year results of a post-authorisation safety surveillance programme.

  Carla E M Hollak, Derralynn Hughes, Ivo N van Schaik, Barbara Schwierin, Bruno Bembi
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  ABSTRACT: Miglustat (Zavesca) is an orally-available substrate reduction therapy (SRT) for treatment of mild-to-moderate type 1 Gaucher disease (GD1) in adult patients unsuitable for enzyme replacement therapy (ERT). Miglustat has not been evaluated in children with GD1, and is not used during pregnancy and breast-feeding. A non-interventional, prospective, web-based safety surveillance programme was initiated at the time of the European launch of miglustat in 2003, and is ongoing. We report the first 5 years of collected data, focusing on neurological manifestations. Data were collected on 122 GD1 patients between March 2003 and April 2008, representing 244 patient-years cumulative miglustat post-authorisation experience. The electronically-captured data collected from participating physicians includes patient demographics, prior and current therapies, baseline disease manifestations and concurrent conditions, disease severity, duration of miglustat exposure, and safety-relevant information. Mean (SD) age at baseline was 46.1 (16.5) years. At baseline, bone disease and neurological manifestations were reported in 55.6 and 28.6% of patients, respectively; the latter included peripheral neuropathy (7.2%) and a wide variety of neurological symptoms and signs. In addition, 23.2% had other health conditions relevant to neurological status. During the reporting period, new neurological manifestations were reported in 23 (18.9%) patients, principally tremor. Thirty-five (28.7%) patients discontinued treatment, predominantly for gastrointestinal (GI) disturbances (11.5%), two-thirds of which occurred during the first 6 months. The safety profile of miglustat in GD1 patients included in the safety surveillance programme is overall consistent with that reported in the registration and other clinical trials, and no new safety finding was identified.
  Pharmacoepidemiology and Drug Safety 06/2009; 18(9):770-7. · 2.53 Impact Factor
• Article: The management of Gaucher disease as a chronic disorder.

  Derralynn Hughes
  Clinical Therapeutics 01/2009; 31S3:S182. · 2.32 Impact Factor
• Article: The binary endocardial appearance is a poor discriminator of Anderson-Fabry disease from familial hypertrophic cardiomyopathy.

  Stavros Kounas, Camelia Demetrescu, Antonios A Pantazis, Andre Keren, Philip J Lee, Derralynn Hughes, Atul Mehta, Perry Mark Elliott
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  ABSTRACT: We compared the frequency of a binary endocardial appearance in patients with hypertrophic cardiomyopathy (HCM) and Anderson-Fabry disease (AFD). A recent study suggested that a binary endocardial appearance is a highly sensitive and specific discriminator of AFD from other causes of hypertrophic cardiomyopathy (HCM). Fourteen patients with AFD (55.4 +/- 9.9 years, 9 men) and 14 patients with HCM (57.2 +/- 10.9 years, 9 men) were randomly selected from a dedicated patient database. Two-dimensional echo images were blindly reviewed by 2 experienced echocardiographers. Maximum left ventricular (LV) wall thickness, LV end-systolic dimension, fractional shortening, and left atrial size were similar in the 2 patient groups. The LV end-diastolic dimension was smaller in patients with HCM (p = 0.04). A binary sign was present in 8 of 28 patients (29%). The sensitivity and specificity of the binary sign as a discriminator of AFD from HCM were 35% and 79%, respectively. A binary sign was present in only 1 patient with LV wall thickness <15 mm. The binary endocardial appearance lacks sufficient sensitivity and specificity to be used as an echocardiographic screening tool.
  Journal of the American College of Cardiology 05/2008; 51(21):2058-61. · 14.16 Impact Factor
• Article: The role of heparin in alleviating complement-mediated acute intravascular haemolysis.

  Deepak Mannari, Christine Liu, Derralynn Hughes, Atul Mehta
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  ABSTRACT: Heparin is commonly used as an anticoagulant but its many other pharmacologic properties are less well known. It has an important effect on complement regulation and has been shown in vitro to inhibit complement-mediated lysis of red cells. Although the beneficial effects of heparin for treatment of haemolytic anaemia were described many decades ago, its use in this scenario is not standard practice. Here we report a case where the use of heparin had a beneficial effect on a life-threatening episode of intravascular haemolysis. We also show unfractionated heparin to be more beneficial than low molecular weight heparin. We suggest that heparin has an important role to play in the management of complement-mediated haemolytic episodes.
  Acta Haematologica 02/2008; 119(3):166-8. · 1.35 Impact Factor
• Source

  Available from: PubMed Central

  Article: Recommendations for the management of the haematological and onco-haematological aspects of Gaucher disease.

  Derralynn Hughes, Maria Domenica Cappellini, Marc Berger, Jan Van Droogenbroeck, Maaike de Fost, Dragana Janic, Theodore Marinakis, Hanna Rosenbaum, Jesús Villarubia, Elena Zhukovskaya, Carla Hollak
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  ABSTRACT: Current knowledge of the haematological and onco-haematological complications of type 1 Gaucher disease has been reviewed with the aim of identifying best clinical practice for treatment and disease management. It was concluded that: (i) Awareness of typical patterns of cytopenia can help clinicians distinguish haematological co-morbidities. (ii) Red blood cell studies and complete iron metabolism evaluation at baseline are recommended. (iii) Haemoglobin levels defining anaemia should be raised and used in Gaucher disease treatment and monitoring. (iv) Surgeons should be aware of potential bleeding complications during surgery in Gaucher patients. The higher incidence of multiple myeloma in Gaucher disease suggests that Gaucher patients should have their immunoglobulin profile determined at diagnosis and monitored every 2 years (patients <50 years) or every year (patients >50 years). If monoclonal gammopathy of undetermined significance (MGUS) is found, general MGUS guidelines should be followed. Future studies should focus on the utility of early treatment to prevent immunoglobulin abnormalities and multiple myeloma.
  British Journal of Haematology 09/2007; 138(6):676-86. · 4.94 Impact Factor
• Article: Middelheim Fabry Study (MiFaS): a retrospective Belgian study on the prevalence of Fabry disease in young patients with cryptogenic stroke.

  Raf Brouns, Rishi Sheorajpanday, Ellen Braxel, François Eyskens, Robert Baker, Derralynn Hughes, Atul Mehta, Therese Timmerman, Marie-Françoise Vincent, Peter Paul De Deyn
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  ABSTRACT: To assess the prevalence of Fabry disease in young patients with cryptogenic stroke. We retrospectively assessed the prevalence of Fabry disease in patients aged 16-60 years that were admitted to ZNA Middelheim Hospital from January 1, 2000 to December 31, 2004 for cryptogenic stroke. We screened for Fabry disease by measurement of alpha-galactosidase A and beta-glucuronidase activity on blood spot. In all patients with abnormal enzymatic activity and in all female patients with low normal values, genetic sequencing of the alpha-GAL-gene was performed. In a population of 103 young patients with cryptogenic stroke that met the in- and exclusion criteria, we were unable to identify any patient with Fabry disease. Based on the results of alpha-galactosidase A and beta-glucuronidase activity, genetic sequencing and the low prevalence of clinical signs and symptoms of Fabry disease in this population, we believe that the true prevalence of Fabry disease in patients with cryptogenic stroke may be less than currently accepted in literature.
  Clinical Neurology and Neurosurgery 08/2007; 109(6):479-84. · 1.58 Impact Factor
• Article: Recommendations for the management of the haematological and onco‐haematological aspects of Gaucher disease1

  Derralynn Hughes, Maria Domenica Cappellini, Marc Berger, Jan Van Droogenbroeck, Maaike De Fost, Dragana Janic, Theodore Marinakis, Hanna Rosenbaum, Jesús Villarubia, Elena Zhukovskaya, Carla Hollak
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  ABSTRACT: Current knowledge of the haematological and onco-haematological complications of type 1 Gaucher disease has been reviewed with the aim of identifying best clinical practice for treatment and disease management. It was concluded that: (i) Awareness of typical patterns of cytopenia can help clinicians distinguish haematological co-morbidities. (ii) Red blood cell studies and complete iron metabolism evaluation at baseline are recommended. (iii) Haemoglobin levels defining anaemia should be raised and used in Gaucher disease treatment and monitoring. (iv) Surgeons should be aware of potential bleeding complications during surgery in Gaucher patients.The higher incidence of multiple myeloma in Gaucher disease suggests that Gaucher patients should have their immunoglobulin profile determined at diagnosis and monitored every 2 years (patients <50 years) or every year (patients >50 years). If monoclonal gammopathy of undetermined significance (MGUS) is found, general MGUS guidelines should be followed. Future studies should focus on the utility of early treatment to prevent immunoglobulin abnormalities and multiple myeloma.
  British Journal of Haematology 07/2007; 138(6):676 - 686. · 4.94 Impact Factor