Alexander Broomfield
Great Ormond Street Hospital
Network
Latest external collaboration on country level. Dive into details by clicking on the dots.
Publication
Featured researches published by Alexander Broomfield.
Brain | 2014
A. Reghan Foley; Manoj P. Menezes; Amelie Pandraud; Michael Gonzalez; Ahmad Al-Odaib; Alexander J. Abrams; Kumiko Sugano; Atsushi Yonezawa; Adnan Y. Manzur; Joshua Burns; Imelda Hughes; B. Gary McCullagh; Heinz Jungbluth; Ming Lim; Jean-Pierre Lin; André Mégarbané; J. Andoni Urtizberea; Ayaz H. Shah; Jayne Antony; Richard Webster; Alexander Broomfield; Joanne Ng; Ann Agnes Mathew; James J. O’Byrne; Eva Forman; M. Scoto; Manish Prasad; Katherine O’Brien; S. E. Olpin; Marcus Oppenheim
Childhood onset motor neuron diseases or neuronopathies are a clinically heterogeneous group of disorders. A particularly severe subgroup first described in 1894, and subsequently called Brown-Vialetto-Van Laere syndrome, is characterized by progressive pontobulbar palsy, sensorineural hearing loss and respiratory insufficiency. There has been no treatment for this progressive neurodegenerative disorder, which leads to respiratory failure and usually death during childhood. We recently reported the identification of SLC52A2, encoding riboflavin transporter RFVT2, as a new causative gene for Brown-Vialetto-Van Laere syndrome. We used both exome and Sanger sequencing to identify SLC52A2 mutations in patients presenting with cranial neuropathies and sensorimotor neuropathy with or without respiratory insufficiency. We undertook clinical, neurophysiological and biochemical characterization of patients with mutations in SLC52A2, functionally analysed the most prevalent mutations and initiated a regimen of high-dose oral riboflavin. We identified 18 patients from 13 families with compound heterozygous or homozygous mutations in SLC52A2. Affected individuals share a core phenotype of rapidly progressive axonal sensorimotor neuropathy (manifesting with sensory ataxia, severe weakness of the upper limbs and axial muscles with distinctly preserved strength of the lower limbs), hearing loss, optic atrophy and respiratory insufficiency. We demonstrate that SLC52A2 mutations cause reduced riboflavin uptake and reduced riboflavin transporter protein expression, and we report the response to high-dose oral riboflavin therapy in patients with SLC52A2 mutations, including significant and sustained clinical and biochemical improvements in two patients and preliminary clinical response data in 13 patients with associated biochemical improvements in 10 patients. The clinical and biochemical responses of this SLC52A2-specific cohort suggest that riboflavin supplementation can ameliorate the progression of this neurodegenerative condition, particularly when initiated soon after the onset of symptoms.
Archives of Disease in Childhood | 2012
Alexander Broomfield; Stephanie Grunewald
Hyperammonaemia is a potentially extremely important indicator of impairment in intermediate metabolism. However, lack of experience in sample handling and confusion about what level is significant, can lead to its devaluation as a test. The aim of this article is to help the non-metabolic specialist to decide when it is appropriate to investigate for hyperammonaemia, to discuss potential investigatory pitfalls and to help in interpretation of results.
JIMD reports , 12 pp. 99-102. (2014) | 2013
J. Baruteau; Alexander Broomfield; V. Crook; Niamh Finnegan; K. Harvey; Derek Burke; M. Burch; G. Shepherd; Ashok Vellodi
Pompe disease (PD) is a severe life-threatening disease in which enzyme replacement therapy (ERT) with alglucosidase alfa is the only treatment available. Recently it has been shown that antibody formation may have a significant adverse effect on response to ERT. We report a cross-reactive immunologic material (CRIM)-positive PD infant who developed severe infusion-associated reactions (IARs) after 15 uneventful months of ERT. We successfully got the child to tolerate the ERT by a desensitisation protocol. We diluted the total amount of standard alglucosidase alfa infusion (20 mg/kg/dose) to 1/100 (0.2 mg/kg/dose). The original infusion rates were maintained. We doubled this dose every week. No premedication was given. In 8 weeks, we reached the standard dose without any IAR. No further reactions have been observed during 6 months of follow-up. Importantly, clinical deterioration that was observed during the period of reduced enzyme delivery has almost completely reversed. We conclude that this protocol was effective in our patient, while being safe and easy to follow, and may be suitable in selected cases.
Archive | 2017
Alexander Broomfield; J. Fletcher; Pauline Hensman; R. Wright; Helen Prunty; J. Pavaine; Simon A. Jones
Glycogen accumulation in the central nervous system of patients with classical infantile onset Pompe disease (IOPD) has been a consistent finding on the few post-mortems performed. While delays in myelination and a possible reduction in processing speed have previously been noted, it has only been recently that the potential for clinically significant progressive white matter disease has been noted. The limited reports thus far published infer that in some IOPD patients, this manifests as intellectual decline in the second decade of life. We present a CRIM negative patient, immunomodulated with rituximab and methotrexate at birth, who despite an initial good clinical response to ERT, at the age of just under 4 years, presented with evolving spasticity in the lower limbs. The investigation of which revealed progressive central nervous system involvement. Given both the earlier onset of the symptoms and consanguineous familial pedigree, extensive biochemical and genetic investigation was undertaken to ensure no alternative pathology was elucidated. In light of these findings, we review the radiology and post-mortems of previous cases and discuss the potential mechanisms that may underlie this presentation.
Journal of Inherited Metabolic Disease | 2017
Su Han Lum; Karolina M. Stepien; Arunabha Ghosh; Alexander Broomfield; Heather J. Church; Jean Mercer; Simon A. Jones; Robert Wynn
Premature death in untreated children with Hurler syndrome (HS) in the first decade of life is largely due to life-threatening cardiopulmonary complications. We examined the long-term survival and cardiopulmonary outcome in 54 children undergoing haematopoietic stem cell transplantation (HSCT) at the Royal Manchester Children’s Hospital from 1985 to 2008. The median age at first HSCT was 15.1 months. Eighteen had graft failure and nine died after first HSCT. Of 18 patients with graft failure, 17 underwent second HSCT and the remaining one was lost to follow-up (LOF). Twelve were alive-and-engrafted after second HSCT. The overall survival at one year and 20-years was the same at 73.7%. Six children were followed up at the referral centers and excluded from cardiopulmonary endpoint review. Of the 33 evaluable children for the cardiopulmonary endpoints, nine (27.3%) had normal cardiac assessment. Of the four children on angiotensin-converting-enzyme inhibitors, two had mild cardiomyopathy and two had aortic valvular replacement. Twenty (60%) had mild/moderate mitral and/or aortic insufficiencies. Two had overnight hypoxia needing nocturnal non-invasive support. Enzyme level and donor chimerism are important predictors of long-term cardiac outcome.
Journal of Inherited Metabolic Disease | 2015
Martin Magner; Veronika Dvorakova; Marketa Tesarova; Stella Mazurova; Hana Hansikova; Martin Zahorec; Katarina Brennerova; V. Bzduch; Ronen Spiegel; Yoseph Horovitz; Hanna Mandel; Fatma Tuba Eminoğlu; Johannes A. Mayr; Johannes Koch; Diego Martinelli; Enrico Bertini; Vassiliki Konstantopoulou; Joél Smet; Shamima Rahman; Alexander Broomfield; Vesna Stojanovic; Carlo Dionisi-Vici; Rudy Van Coster; Eva Morava; Wolfgang Sperl; Jiri Zeman; Tomas Honzik
Martin Magner & Veronika Dvorakova & Marketa Tesarova & Stella Mazurova & Hana Hansikova & Martin Zahorec & Katarina Brennerova & Vladimir Bzduch & Ronen Spiegel & Yoseph Horovitz & Hanna Mandel & Fatma Tuba Eminoğlu & Johannes Adalbert Mayr & Johannes Koch & Diego Martinelli & Enrico Bertini & Vassiliki Konstantopoulou & Joél Smet & Shamima Rahman & Alexander Broomfield & Vesna Stojanović & Carlo Dionisi-Vici & Rudy van Coster & Eva Morava & Wolfgang Sperl & Jiri Zeman & Tomas Honzik
Journal of Inherited Metabolic Disease | 2015
Alexander Broomfield; Mary G. Sweeney; Cathy Woodward; Carl Fratter; Andrew M. Morris; J. V. Leonard; Lara Abulhoul; Stephanie Grunewald; Peter Clayton; Michael G. Hanna; Joanna Poulton; Shamima Rahman
Journal of Inherited Metabolic Disease | 2015
Martin Magner; Veronika Dvorakova; Marketa Tesarova; Stella Mazurova; Hana Hansikova; Martin Zahorec; Katarina Brennerova; V. Bzduch; Ronen Spiegel; Yoseph Horovitz; Hanna Mandel; Fatma Tuba Eminoğlu; Johannes A. Mayr; Johannes Koch; Diego Martinelli; Enrico Bertini; Vassiliki Konstantopoulou; Joél Smet; Shamima Rahman; Alexander Broomfield; Vesna Stojanovic; Carlo Dionisi-Vici; Rudy Van Coster; Eva Morava-Kozicz; Wolfgang Sperl; Jiri Zeman; Tomas Honzik
Journal of Inherited Metabolic Disease | 2015
Martina Huemer; Céline Bürer; Pavel Ješina; Viktor Kožich; Markus A. Landolt; Terttu Suormala; Brian Fowler; P. Augoustides Savvopoulou; E. Blair; Katarina Brennerova; Alexander Broomfield; L. De Meirleir; Gülden Gökçay; J. Hennermann; P. Jardine; J. Koch; Stefan Lorenzl; Amelie S. Lotz-Havla; J. Noss; Rossella Parini; Heidi Peters; Barbara Plecko; F. J. Ramos; Andrea Schlune; K. Tsiakas; M. Zerjav Tansek; Matthias R. Baumgartner
Journal of Inherited Metabolic Disease | 2010
Alexander Broomfield; Anupam Chakrapani; J. E. Wraith
Collaboration
Dive into the Alexander Broomfield's collaboration.
Central Manchester University Hospitals NHS Foundation Trust
View shared research outputs