Models of care to better meet patient needs:

Lysosomal Storage disorders Clinician Perspective

Carolyn Ellaway MBBS PhD FRACP CGHGSA

Sydney Children’s Hospital Network

Disciplines of Paediatrics and Genetic Medicine University of Sydney

Lysosomal Storage Disorders

Prevalence 1: 5,000 - 8000

Mucopolysaccharidoses Prevalence 1: 25,000

MPS I Incidence 1:100,000

Lysosomal Storage disorders

Individually Rare – Collectively Numerous

Lysosomal Storage Disorders

Prevalence 1: 5,000 - 8000

Clinical Manifestations of MPS Disorders

Phenotype Macrocephaly Progressively coarse facial features Macroglossia Corneal clouding Hepatosplenomegaly Inguinal, umbilical hernias

Ear, Nose and Throat (ENT) Chronic rhinorrhoea Recurrent otitis media Enlarged tonsils and adenoids Obstructive sleep apnoea Hearing loss

Cardiac Cardiomyopathy Valve disease Respiratory Recurrent lower respiratory tract infections Reactive airways disease Neurodevelopmental Developmental delay Cognitive impairment Behavioural problems Seizures Hydrocephalus

Orthopaedic / Musculoskeletal Dysostosis multiplex Lumbar kyphosis

Mucopolysaccharidosis Type I Deficiency of α-L-iduronidase Multisystem Involvement Chronic Progressive Course Spectrum of Clinical Severity

SEVERE ATTENUATED

Treatment of lysosomal storage disorders

Supportive Care Management of Specific Complications Haematopoietic Stem Cell Transplantation MPS I, II, VI Enzyme Replacement Therapies:

MPS I, II, VI Pompe disease Fabry disease Gaucher disease

Other: Substrate reduction Chaperone therapies Gene therapy

Hollak & Wijburg Treatment of Lysosomal storage disorders: successes and challenges JIMD 2014 37:587 - 598

Optimal management involves a multidisciplinary team approach

ENT & General surgeon

Cardiologist

Geneticist/ Metabolic Specialist

Respiratory Sleep

Physician

Primary Care

Physician

Orthopaedic Surgeon

Neurologist Neurosurgeon

Patient

Enzyme Replacement

Therapy

Physical & Occupational

Therapy

Genetic Counseling

Other novel therapies

Nutritional & Diet

Therapy

Speech Therapy

Psychosocial Therapy

Kishnani et al. Genet Med. 2006;8:267-288.

Lysosomal storage disorders: Gaps in patient care

Delayed diagnosis Access to specific therapies Dedicated multidisciplinary management clinics Limited and variable access to community

services General paediatrician GP Allied health professional Equipment & other resources

Example of a model of care to better meet patient needs

Rett syndrome Multidisciplinary Management clinic

Children’s Hospital at Westmead, Sydney

Established in February 2000 Aim to provide a comprehensive management

service and support for patients with Rett syndrome and their families

What is Rett syndrome ? Severe neurodevelopmental disorder, occurring mainly in females MECP2 gene on the X chromosome Following normal early development, there is developmental regression with loss of communication and hand function and profound intellectual impairment. Other features include: Hand stereotypies Breathing dysfunction Scoliosis Epilepsy Poor growth Feeding difficulties Gait and/or truncal ataxia Prevalence 1:10,000 females

Rett Syndrome Multidisciplinary Management Clinic Team

Geneticist/Paediatrician Genetic Counsellor Clinic Coordinator Dietician Physiotherapist

Occupational Therapist Speech Therapist Dentist Music Therapist

Rett syndrome: Management Issues

General health Seizure management Prolonged QTc Sleep Dental assessment Scoliosis Mobility Contractures

Nutrition Feeding abilities Communicative abilities Hand function Equipment needs Genetic counselling Family support

Rett Multidisciplinary Management Clinic: Structure Management clinic:

Pre-clinic intake Pre-clinic meeting

Each patient and her family

sees:

Dentist "Medical" Team

Staff Post-Clinic meeting

Post-clinic Investigations, referrals,

follow up, liason report preparation

Collation and distribution of

report

"Therapy" Team

Attendance ~ every 1-2 years

Diagnostic clinic: Geneticist

Genetic Counsellor

Rett Multidisciplinary Management Clinic: Outcomes Since 2000:

Increased awareness and understanding of Rett syndrome Earlier diagnosis and referral

Early diagnosis and intervention improves morbidity and the long term outlook.

Education & increased confidence in primary care practitioners and local allied health professionals caring for girls and now adults with Rett syndrome

Rett Mx Team always available to be contacted by local teams for advice

Increased confidence and empowerment of parents/carers to advocate for their daughters

Patients seen until 18 years at CHW and then transitioned to Adult Disability clinic at Westmead Hospital

Liaison and collaboration between clinic and lab based research teams Well placed to commence clinical trials High degree of satisfaction reported by families attending the clinic

How can we improve patient care ? Multidisciplinary Management Clinics

Target patient population Dedicated team Clinic coordination Funding Resources

Be the change you wish to see in the world M.Ghandi

“Why isn't there a multidisciplinary management clinic for patients with LSD just like the Rett syndrome Multidisciplinary Management clinic?”

Mother of a girl with Rett syndrome and a son with MPS III (2013)