Rare Diseases

Background

• Rare disease = affecting less than 1 in 2000 people

• > 7000 known

• 2 million Australians affected

  • 1 in 12 people

• 300 million globally

• 80% present in childhood

• 30% living with a rare disease die before 5 years of age

• 80% have a genetic origin

• Non genetic causes including rare cancers, infections, autoimmune disease or environment related conditions

• 50% of those with a rare disease are undiagnosed

• Those who are diagnosed on average

  • Have seen >6 doctors

  • Waited > 3 years for a diagnosis

  • 30% had a misdiagnosis

New born screening

• Heel prick test on day 2 or 3

• Tests for the following -

Endocrine disorders

• Congenital adrenal hyperplasia (21-hydroxylase deficiency)

• Primary congenital hypothyroidism

Metabolic disorders

Amino acid disorders

• Argininosuccinic aciduria

• Citrullinemia type I

• Homocystinuria

• Maple syrup urine disease

• (Classic) Phenylketonuria (PKU) - including hyperphenylalinemias (PAH and pterin enzyme deficiencies)

• Tyrosinemia types II and III 

Fatty acid oxidation disorders

• Carnitine acylcarnitine translocase deficiency

• Carnitine palmitoyltransferase I deficiency

• Carnitine palmitoyltransferase II deficiency 

• Carnitine uptake defect 

• Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency 

• Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency

• Trifunctional protein deficiency 

• Very long-chain acyl-CoA dehydrogenase deficiency

Organic acid disorders

• 3-hydroxy-3-methylglutaric aciduria

• β-ketothiolase deficiency

• Glutaric Acidemia Type II multiple acyl-CoA-dehydrogenase deficiency)

• Glutaric Acidemia Type I

• Holocarboxylase synthase deficiency 

• Isovaleric Acidemia 

• Methylmalonic Acidemia (Cobalamin A&B disorders) 

• Methylmalonic Acidemia Cobalamin defects C,D v2 

• Methylmalonic Acidemia (Methylmalonyl-CoA Mutase)

• Propionic Acidemia 

Other disorders 

• Cystic fibrosis

Common Challenges

• Struggle for timely and accurate diagnosis

• Limited care and support options

  • Burden of explanation on patients and carers when talking to doctors

  • Scepticism from health professionals about consider rare diseases due to rarity

  • Challenges accessing expert sin their disease in Australia

  • Paucity of centres of clinical excellence

  • Difficulties coordinating holistic health and social care

• Lack of research into rare diseases

  • Lack of high quality rare disease registries and natural history studies

  • Australia’s small population means we don’t have many clinical trials

• Financial impacts

  • 10% of all inpatient hospital cost due to people with rare disease

  • Families have many under recognised hidden costs

  • Loss of time

Priority populations

• ATSI

• Cultural and linguistically diverse

• Socioeconomic disadvantage

• Rural and remote

• Undiagnosed rare diseases

Ideal World

People living with a rare disease would have

• Timely diagnosis

• Proactive mental health support

• Person and family centred care in a specialist centre or network with effective communication with their GP

• Access to support groups

Mental Health and wellbeing

• 95% of those living with a rare disease had felt anxious or worried

• 90% had felt low

• 88% had felt emotional exhausted

• 42% had depression scores indicating moderate to severe

• 23% had anxiety scores indicating more to severe

• Anxiety and depression frequently co-occurred

• Isloating and loneliness was common

• High burden of care with few proven treatment options

• Prolonged stress associated with high levels of uncertainty

• Many rare diseases have no obvious physical features

• Mother of children with rare diseases visit their GP much less frequently that those with health children

• Very few families have been offered psychological support when their children has a rare disease diagnosis

Mental health tips

• Proactively ask about mental health if rare disease

• Discuss strategies for maintaining mental wellbeing focusing on a strengths based approach

• Link people with support, information and care, including to rare disease organisations

• Reduce stigma by starting the conversation and discussing how common mental health and wellbeing challenges are

• Help to address day-to-day challenges may be the greatest part in caring for your patients mental health

Key Mental Health and Wellbeing Resources

• Head to Health - a digital health resource hub 

• Carer Gateway- free programs and resources for carers

• Kindred (NSW)- For families raising children with disability

• Kalparrin (WA)- Supporting families with children of additional needs 

• My Time- Supported playgroups for families with children with disability or other additional needs

• Siblings Australia- supporting siblings of children with chronic illnesses and disabilities

• Yarn Safe- Culturally safe advice for Aboriginal and Torres Strait Islander young people

• Embrace Multicultural Mental Health- resource platform for healthcare providers and CALD communities 

Respect and effective comunication

• Check

• Listen and listen again

  • Eye contact, put your opinions aside, don’t interject, tune into body language, look for nuances - thoughts and feelings

• Communicate

• Be honest

• Update

• Signpost

• Coordinate

• Collaborate

• Recap

• Support

Delivering a rare diagnosis

• Be honest

• Be open

• Check in

• Keep your patient informed

Trauma Based Care

The "4 R's" for a trauma-informed proactive approach:

• Realize how trauma affects the individuals and communities you serve in your practice

• Recognize the symptoms of trauma in your patients

• Respond to patients in a trauma-informed way

• Resist re-traumatisation of patients

Diagnostic Odyssey

• Takes > 3 years to receive a diagnosis

• Many have their lived experience denied or not listened to

• Many patients end up seeing multiple specialists without anyone ever joining the dots

• Medical ping pong

This diagnostic odyssey is even harder when you add in

• ATSI + CALD communities

• Rural and remote conditions

Diagnosis

• Family GENES

• Group of congenital abnormalities

• Extreme or exceptional presentation of common conditions

• Neurodevelopmental delay or degeneration

• Extreme or exceptional pathology

• Surprising laboratory values

• Family = Multiple affected siblings or individuals

Once suspected

• Thorough history of all symptoms, potentially from birth, including timelines

• Three generation family history

• Thorough exam

• Compile a list of all the investigations findings so far

Biases

• Diagnostic momentum bias - Once labelled with a condition, what started out as a possibility gathers momentum until it becomes seen as definite and all other possibilities are excluded

• Framing Effect Bias - Be aware of how colleagues and patients frame potential outcomes and contingencies of the clinical problem

• Premature Closure - Accept a diagnosis before it has been fully verified

Artificial Intelligence

• Of the growing list of AI assisted diagnostic tools for rare diseases, two we highly recommend that are specific to rare diseases are FindZEBRA and PubCaseFinder.

Genomics

• Single gene test

• Chromosomal microarray

• Genomic tests

Outcomes of genetic tests

• Diagnosis

• Variance on unknown significance

• No diagnosis

• Incidental finding

Referral after diagnosis

• Centre for Genetics Education directs clinicians to the most common genetic conditions diagnosed after Medicare-funded genomic testing for developmental delay and/or multiple congenital anomalies

• GeneREVIEWS is an international point-of-care resource for busy clinicians. It provides clinically relevant and medically actionable information covering diagnosis, management, and genetic counselling for patients and their families

• Genetic and Rare Diseases Information Center (GARD) is a US based website that gathers information about rare and genetic diseases from reliable research databases to make it easier for patients, families, and caregivers to find information. Each disease page also lists resources and organisations to support the needs of children and adults living with a rare disease

• Rare Awareness Rare Education (RARE) Portal is an Australian rare disease information database containing current, reliable and straightforward information and resources for all rare disease stakeholders

• Rare Voices Australia (RVA) is the national peak body for Australians living with a rare disease. See their A-Z Support Directory

• UNIQUE is a UK based website providing information for families with a rare chromosomal condition

Resources

• Rare Diseases 101 - Medics 4 Rare Diseases M4RD

• National Strategies Action for Rare Disease - Health.gov.au (2020)

• RARE Portal - Rare Awareness Rare Education Portal

• Genomics in GP - RACGP