The Devastating Impact of a Late Diagnosis in Rare Diseases

Over the past two decades, I have had the privilege of witnessing in Mexico a few cases where patients with rare diseases received an early diagnosis. It is a wonderful moment, as it opens the door to timely treatment and better health outcomes.

This generally occurs when there are multiple members within the family or community affected by the same condition, or when there is a physician with both knowledge and a true vocation for service, as well as a family member who fights for their loved one.

Unfortunately, in most cases this is not what happens. Instead, we witness the family’s ordeal, the progressive deterioration caused by the disease, and the inexorable loss of vital functions and quality of life.

When the first symptoms of a rare disease appear — sometimes subtle, others more severe — a journey filled with uncertainty begins for the patient and their family.

This journey, internationally known as the "diagnostic odyssey," can last for years, and it is not uncommon for the diagnosis to arrive late, when the damage to the patient’s health is already significant and the silent, relentless progression of the disease has impaired multiple vital functions; and most painfully, when the opportunities for timely intervention and the expectation of meaningful health outcomes have drastically diminished.

This question — “Why didn’t we know earlier?” — expresses not only frustration but also a profound pain shared by thousands of families around the world.

The First Symptoms

Early symptoms of rare diseases are often nonspecific: muscle weakness, recurrent infections, mild dyspnea, osteoarticular problems, fatigue, visual or auditory disturbances, or difficulties in walking, among many others. Due to their multisystemic nature, these signs may be mistaken for more common conditions and attributed to more frequent causes. Thus, physicians may initially overlook the possibility of a rare disease, and the patient may be seen by multiple specialists before receiving a definitive answer.

In Europe, the average time between the first symptoms and the correct diagnosis is 4.7 years (1). In Spain, delays average 6.18 years (2). In Latin America, where healthcare systems face additional challenges, the delay may be even greater; regional studies show averages of five to seven years (3). In Mexico, recent estimates from the Mexican Rare Diseases Registry report a delay of approximately seven to eight years, with some patients seen by as many as six to eight specialists before the final diagnosis (4).

This delay is not merely a number: it represents years of uncertainty, confusion, incomplete treatments, hospitalizations, repeated tests, and rising expenses. In testimonies included in international qualitative analyses, many families describe cycles of consultations where they received incorrect or partial diagnoses, unnecessarily prolonging emotional and physical suffering (5).

Consequences 

By the time a diagnosis is finally reached, the disease is often already advanced. In slowly progressive conditions, each month without diagnosis may represent accumulated organ damage: pulmonary impairment, cardiopathies, renal injury, neurodegeneration, or progressive loss of mobility.

The evidence is clear. In pediatric patients, diagnostic delay increases the risk of neurological complications, developmental delays, academic difficulties, and future disabilities (6). In adults, it may limit the effectiveness of specific therapies or prevent early multidisciplinary care that could have changed the disease’s course.

For families, the emotional burden is particularly severe. Uncertainty generates anxiety, feelings of guilt, exhaustion, stress, and loss of confidence in the healthcare system. International studies in clinical psychology show that caregivers of patients with rare diseases have high rates of anxiety and stress associated with the absence of diagnosis and the ongoing search for answers (7).

Why Does Diagnosis Take So Long? 

Diagnostic delay in rare diseases is not caused by a single factor; it is multifactorial. Among the most common causes are:

• Nonspecific symptoms resembling more common conditions.

• Multisystemic nature leading to fragmented clinical pathways across specialties.

• Limited training in rare diseases within medical school curricula (8).

• Scarcity of specialized centers and long waiting times due to limited healthcare infrastructure.

• Higher prevalence in rural areas where access to specialized care is significantly slower.

• Limited access to genetic and high-complexity testing, especially in publicly funded systems (9), commonly restricted to large hospital centers and often financed by the pharmaceutical industry.

• Lack of fast-track referral protocols between primary care and genetic or rare disease specialists.

Medical literature highlights the high number of consultations prior to diagnosis. A multicenter study showed that patients visited an average of seven different specialties before reaching the final diagnosis (3). This can occur because, in early stages, symptoms are interpreted as common conditions, delaying clinical suspicion of a rare disease.

This combination of factors explains why patients may undergo unnecessary surgeries, partial treatments, or interventions focused solely on symptoms rather than the root cause (10).

Real Stories Illustrating the Human Impact

Various qualitative and narrative studies have documented profound testimonies on the experience of late diagnosis:

• Case 1. A teenager with motor symptoms and mild cardiopathy was treated for over five years as having idiopathic cardiomyopathy. Only after genetic sequencing was a mitochondrial myopathy diagnosed. By then, respiratory insufficiency and advanced neuromuscular deterioration were already present (10).

• Case 2. A child with recurrent infections, hepatosplenomegaly, and growth delay was seen by multiple specialists — gastroenterology, immunology, nephrology — over seven years before being diagnosed with a rare immunodeficiency. By the time it was confirmed, damage to vital organs was irreversible (6).

• Case 3. An adult woman treated for osteoarthritis, osteoporosis, and progressive dyspnea was finally diagnosed at age 38 with a rare lysosomal disease. Similar testimonies indicate that early diagnosis enables interventions with greater functional impact (11).

These stories — common in specialized literature — remind us that in rare diseases, time is a clinical determinant.

Quality of Life and Healthcare Systems

The impact of late diagnosis is profound:

• Increased accumulated disability

• Loss of autonomy

• Need for permanent care

• Higher risk of severe events, including hospitalizations or premature death

• Reduced opportunities for social, educational, or labor inclusion

• Growing need for palliative or intensive multidisciplinary care

From an economic and public health perspective, diagnostic delay significantly increases system costs: more studies, frequent hospitalizations, repeated or unnecessary interventions, multiple consultations, and delayed treatments (12). Family costs and work absenteeism also rise.

How Can We Prevent This From Continuing?

International evidence suggests clear measures:

• Stronger medical training in rare diseases and early identification

• National protocols for early clinical suspicion

• Consolidation of highly specialized referral centers

• Timely access to genetic and molecular tests nationwide

• Integration of digital tools and artificial intelligence algorithms to support early detection (13)

• Close collaboration between the healthcare system, industry, patient organizations, and the scientific community

Mexico has begun advancing with initiatives such as the Mexican Rare Diseases Registry, but structural challenges remain to reduce diagnostic times and improve the patient experience (4).

Conclusion

Late diagnosis in rare diseases is not simply an administrative delay: it is a health determinant. A disease may progress silently for years, causing irreversible damage and profound emotional, social, and economic burdens. As healthcare professionals, business sector leaders, or actors in science and technology, we must transform the question “Why didn’t we know earlier?” into an invitation to improve early detection, strengthen clinical suspicion, and build faster and more humane diagnostic pathways.

Time — currently the main enemy of the patient with a rare disease — must become their greatest ally to ensure the ultimate goal of any health system: greater and better quality of life, and a dignified future.

References

Faye F., et al. (2024). Time to diagnosis and determinants of diagnostic delays for people living with rare diseases. European Journal of Human Genetics. Benito-Lozano J., et al. (2022). Diagnostic delay in rare diseases: Spanish rare diseases registry. Orphanet Journal of Rare Diseases. Wainstock D., et al. (2023). Advancing rare disease policy in Latin America. Orphanet Journal of Rare Diseases. Aspiros C. E., et al. (2024). First-year results from the Mexican Rare Diseases Registry. Journal of Rare Diseases. Cribbs K., et al. (2025). Real-World Rare Disease Patient Journeys: A Qualitative Assessment. Journal of Evaluation in Clinical Practice. Pavisich K., et al. (2024). Diagnostic odyssey in pediatric rare diseases. Journal of Rare Diseases. Dumbuya J. S., et al. (2025). Impact of rare diseases on caregiver quality of life. Frontiers in Genetics. Phillips C. (2024). Time to diagnosis and medical uncertainty in rare diseases. Orphanet Journal of Rare Diseases. Carino T., et al. (2021). The diagnostic journey for rare disease patients: scaling sustainable solutions. Avalere/Global Commission. Cribbs K. A., et al. (2025). Case-based examination of diagnostic delays in rare disease. Journal of Evaluation in Clinical Practice. Imran M. (2025). Delayed diagnosis and long-term complications of a rare lysosomal disorder. Journal of Rare Diseases. Batista L. R., et al. (2024). Repercussions of diagnostic delay of rare diseases. Research, Society and Development. Chaudhary A., et al. (2025). Strategies for early detection in rare diseases: a comprehensive literature review. Annals of Rare Disease Research. Siegel I. J., et al. (2025). Diagnostic delays in rare genetic disorders: systematic review. European Journal of Medical Genetics.