Shining a Light on Rare Diseases: An Interview with Dr Joaquim Sá, Unilabs Genetics

According to WHO, rare diseases affect around 400 million people worldwide. Predominantly genetic, the more than 6000 identified rare diseases present a challenge when it comes to diagnosis and treatment. 

On Rare Disease Day, we have spoken with one of our geneticists, Dr Joaquim Sá, to delve into the diagnosis of these conditions and future advancements.

How does Unilabs contribute to rare disease diagnosis and understanding through genetic analysis?

At Unilabs, we offer genetic testing services, including whole exome sequencing, targeted gene panels, FISH, cytogenetics, and other molecular genetic tests, which help identify genetic variations associated with rare diseases.

Our team of clinical genetics laboratory specialists and medical genetics physicians interprets results and guides healthcare providers and patients in understanding the implications of genetic findings.

We also actively engage in research collaborations with academic institutions, pharmaceutical companies, and other research entities. These partnerships contribute to advancing knowledge about rare diseases and developing new diagnostic tools and treatments.

For instance, we are committed to contributing to genetic databases by sharing anonymised genetic data with researchers and participating in initiatives such as the Genome PT Project. This sharing of data facilitates research into rare diseases and contributes to a better understanding of their underlying genetic causes.

Furthermore, we participate in educational programmes and outreach activities to raise awareness about rare diseases and the importance of genetic testing. This effort aims to increase early diagnosis and provide appropriate medical interventions for individuals with rare genetic conditions.

What are some of the most common rare diseases that Unilabs encounters in its genetic testing services, and what are the rarest?

At Unilabs, we encounter a diverse array of rare diseases in our genetic testing services. Some of the more common include Cystic Fibrosis, a genetic disorder affecting the respiratory, digestive, and reproductive systems; Huntington's Disease, a neurodegenerative disorder leading to progressive motor and cognitive decline; Duchenne Muscular Dystrophy, characterised by progressive muscle degeneration and weakness; Spinal Muscular Atrophy, a group of genetic disorders affecting the motor neurons of the spinal cord, leading to muscle weakness; Hereditary Hemochromatosis, causing excessive iron absorption and iron overload in the body; Familial Hypercholesterolemia, resulting in high levels of cholesterol in the blood and leading to cardiovascular issues; Neurofibromatosis, a group of genetic disorders causing tumours to form on nerve tissue; Marfan Syndrome, a connective tissue disorder affecting the heart, eyes, and skeleton; Polycystic Kidney Disease, characterised by the formation of cysts in the kidneys; and Fragile X Syndrome, causing intellectual disabilities and behavioral challenges.

As for the rarest diseases, pinpointing specific conditions is challenging due to their extremely low prevalence. Some ultra-rare diseases may only affect a handful of individuals globally. Examples of such rare diseases diagnosed at Unilabs include Fibrodysplasia Ossificans Progressiva, where soft tissues progressively turn into bone, and cases where individuals present with two or three rare diseases, an occurrence thought to be one in twenty diagnoses. However, such diagnoses have been elusive in clinical practice, outside of research laboratories. Yet, in the last year, Unilabs diagnosed one person with two rare diseases, each with a prevalence of less than one in 20,000, making the probability a priori less than one in 400,000.

Can you share any success stories or impactful cases where genetic testing has made a difference in diagnosing or managing a rare disease?

Genetic testing has proven transformative in numerous cases, bringing hope and tailored treatments to individuals facing rare diseases.

At Unilabs, our commitment to precision in medical genetics has led to remarkable outcomes. One poignant example involves a child diagnosed with Leber's congenital amaurosis due to a variant in the RPE65 gene. Initially facing the prospect of vision loss in her teens, precise genetic diagnosis made her eligible for groundbreaking gene therapy – subretinal gene augmentation. Today, years after commencing treatment, she thrives, a testament to the life-changing impact of genetic intervention.

In cases of stunted growth, accurate diagnosis has empowered children to receive growth hormone therapy. Despite its considerable cost, the molecular diagnosis of Silver-Russell syndrome in several children has facilitated free treatment through National Health Service.

In other instances, diagnosis has opened doors to international experimental drug therapies, as evidenced by the case of two brothers diagnosed with Cockayne syndrome. Their inclusion in novel treatment trials underscores the pivotal role of genetic testing in exploring innovative therapeutic avenues.

Unilabs' expertise extends to prenatal diagnosis, offering both solace and actionable insights to expecting parents. While some diagnoses unveil serious and incurable conditions, others provide reassurance and guidance. For instance, the identification of achondroplasia empowers couples with comprehensive genetic counseling and specialised medical support prenatally, fostering informed decision-making and tailored care.

In the realm of fetal ultrasound anomalies, our WES-trio testing has been instrumental. When results return normal and anomalies are deemed non-major, families receive invaluable peace of mind, knowing there's no significantly increased risk for their future newborn. Contributing to such reassurance is a privilege we hold dear at Unilabs.

With advancements in genetic technologies, what do you see as the future of rare disease diagnosis and treatment?

With advancements in genetic technologies, the future of rare disease diagnosis and treatment appears promising, marked by several key trends and developments.

Improved genetic testing, including transcriptome and whole genome sequencing, is becoming more accessible in clinical practice. This accessibility promises a 5% increase in the diagnostic yield of neurodegenerative diseases or polymalformation syndromes.

Faster and more accurate diagnosis is facilitated by the integration of Artificial Intelligence and machine learning into genetic analysis. These applications enable swift and precise interpretation of genetic data, aiding in the diagnosis of rare diseases.

Expanded preconception and prenatal screening now allow for the screening of couples for thousands of diseases before conception, as well as testing for diseases from the first trimester of pregnancy. 

Precision medicine approaches, such as targeted therapies and gene-editing technologies like CRISPR-Cas9, hold the potential to address specific genetic abnormalities underlying rare diseases, offering revolutionary treatment options.

Increased collaboration and data sharing between researchers, healthcare providers, and patient advocacy groups are driving a more comprehensive understanding of rare diseases. These efforts accelerate the development of diagnostics and treatments, supported by numerous European networks in the field.

Telemedicine stands to improve access to specialists in rare diseases, streamlining consultations between patients and doctors more efficiently than current practices.

Growing awareness and advocacy for rare diseases have resulted in increased research funding and initiatives dedicated to understanding and treating these conditions. Today, most new drugs approved for sale each year are related to rare diseases.

Despite these advancements, challenges such as ethical considerations, data privacy, and equitable access to emerging technologies must be addressed. Continued collaboration between researchers, healthcare professionals, and policymakers will be crucial to realising the full potential of genetic technologies in the diagnosis and treatment of rare diseases.