Uma Ramaswami

Consultant

Research area

Lysosomal Storage Disorders, Paediatric Familial Hypercholesterolaemia, other Inherited Metabolic Disorders.

Research summary

The Lysosomal storage disorders (LSDs) are a group of rare inherited disorders. They are usually due to genetic lesions giving rise to mutant enzymes which disturb diverse metabolic pathways. The clinical disorders typically result from organ and cellular dysfunction due to substrate accumulation.

Our work has explored the underlying pathogenesis of LSDs, described the clinical phenotype of the disorders, and established the role of treatments including enzyme replacement therapy.

Over the past decade, we have in partnership, studied the natural history of Fabry Disease in children and identified key early clinical markers of disease severity, and have also undertaken pivotal clinical trials of enzyme therapy in children with LSDs.

Patient involvement

Having been the lead clinician for the paediatric LSD service in Cambridge, followed by a two year secondment to the largest paediatric lysosomal unit in Manchester, I moved to the Royal Free Hospital in 2013. I have joined a dynamic team who lead the way in clinical service, research and development in this field. I currently support the Transition and young adult service at RFH providing a one stop multidisciplinary service for late adolescence and young adults with LSDs; and participating in the ongoing clinical research programme for Fabry Disease in particular and other LSDs.

Since 2012, I have also been the Clinical Lead for the National Paediatric Familial Hypercholesterolaemia Register and work closely alongside Professor Steve Humphries, Professor of Cardiovascular Genetics at UCL. The primary goal of this register is to capture data on the management of paediatric FH in the UK, and in particular the use and safety of statins in children.

With recent UK Cardiovascular Diseases and Cascade Screening initiatives, this is an area of increasing importance and the Royal Free already has a well-established adult lipid clinic. I currently review children with FH in the paediatric clinic with the ultimate goal of providing a comprehensive multidisciplinary service.

Publications

Mehta A, Kuter DJ, Salek SS, Belmatoug N, Bembi B, Bright J, Vom Dahl S, Deodato F, Di Rocco M, Goker-Alpan O, Hughes DA, Lukina EA, Machaczka M, Mengel E, Nagral A, Nakamura K, Narita A, Oliveri B, Pastores G, Pérez-López J, Ramaswami U, Schwartz IV, Szer J, Weinreb NJ, Zimran A. Presenting signs and patient co-variables in Gaucher disease: outcome of the Gaucher Early Diagnosis Consensus (GED-C) Delphi initiative. Intern Med J. 2018.
Nordin S, Kozor R, Baig S, Abdel-Gadir A, Medina-Menacho K, Rosmini S, Captur G, Tchan M, Geberhiwot T, Murphy E, Lachmann R, Ramaswami U, Edwards NC, Hughes D, Steeds RP, Moon JC. Cardiac Phenotype of Prehypertrophic Fabry Disease. Circ Cardiovasc Imaging. 2018. 11(6):e007168
Nordin S, Kozor R, Medina-Menacho K, Abdel-Gadir A, Baig S, Sado DM, Lobascio I, Murphy E, Lachmann RH, Mehta A, Edwards NC, Ramaswami U, Steeds RP, Hughes D, Moon JC. Proposed Stages of Myocardial Phenotype Development in Fabry Disease. JACC Cardiovasc Imaging. 2018. pii: S1936-878X(18)30307-3
Beaton B, Ramaswami U, Hughes DA, Proctor I, Mehta A. Abundant pseudo-Gaucher cells result in delay in diagnosis of plasma cell myeloma. Br J Haematol. 2018 Aug;182(4):465
Geberhiwot T, Moro A, Dardis A, Ramaswami U, Sirrs S, Marfa MP, Vanier MT, Walterfang M, Bolton S, Dawson C, Héron B, Stampfer M, Imrie J, Hendriksz C, Gissen P, Crushell E, Coll MJ, Nadjar Y, Klünemann H, Mengel E, Hrebicek M, Jones SA, Ory D, Bembi B, Patterson M; International Niemann-Pick Disease Registry (INPDR). Consensus clinical management guidelines for Niemann-Pick disease type C. Orphanet J Rare Dis. 2018. 13(1):50
Lavalle L, Thomas AS, Beaton B, Ebrahim H, Reed M, Ramaswami U, Elliott P, Mehta AB, Hughes DA. Phenotype and biochemical heterogeneity in late onset Fabry disease defined by N215S mutation. PLoS One. 2018. 13(4):e0193550
Humphries SE, Cooper J, Dale P, Ramaswami U; FH Paediatric Register Steering Group. The UK Paediatric Familial Hypercholesterolaemia Register: Statin-related safety and 1-year growth data. J Clin Lipidol. 2018. 12(1):25-32
Beck M, Hughes D, Kampmann C, Pintos-Morell G, Ramaswami U, West ML, Giugliani R. Long-term outcomes with agalsidase alfa enzyme replacement therapy: Analysis using deconstructed composite events. Mol Genet Metab Rep. 2017. 14:31-35
Bird S, Hadjimichael E, Mehta A, Ramaswami U, Hughes D. Fabry disease and incidence of cancer. Orphanet J Rare Dis. 2017. 12(1):150
Kalkum G, Pitz S, Karabul N, Beck M, Pintos-Morell G, Parini R, Rohrbach M, Bizjajeva S, Ramaswami U. Paediatric Fabry disease: prognostic significance of ocular changes for disease severity. BMC Ophthalmol. 2016. 16(1):202.