Alphamanosidosis is a rare, serious and difficult to diagnose disease that affects a small number of people in the world, and whose life often depends on early diagnosis and appropriate treatment. According to Orphanet data , it affects only about 1/500,000 live births.
This disease, of genetic origin, is characterized by immune deficiency, facial and skeletal abnormalities, as well as hearing impairment and intellectual disability.
In this report, we gather two key testimonies to understand the reality of alpha-mannosidosis: Jordi Cruz, director of the Lysosomal MPS Association, and Dr. Álvaro Hermida, from the Unit of Diagnosis and Treatment of Metabolic Diseases in Santiago de Compostela. Both offer us a broad and detailed vision of what this pathology is and what it implies for patients, their families and the healthcare professionals who deal with this disease on a daily basis.
A difficult diagnosis, an uncertain future
“The most difficult aspect of alpha-mannosidosis is not just the disease itself, but the time that passes before symptoms appear—until those symptoms point to a clear diagnosis that allows us to begin taking action,” says Jordi Cruz, who for more than two decades has led the fight for the recognition of rare diseases such as alpha-mannosidosis through theLysosomal MPS Association. For him, the starting point and the key to everything else lies inearly diagnosis.
“Because doctors are unfamiliar with these rare conditions, they may not suspect that a patient has a rare disease. It takes a long time to identify it, and in the meantime, patients and their families suffer,” Cruz laments. Unfortunately, this also leads to patients being misdiagnosed with conditions that have nothing to do with these rare diseases, which delays early access to appropriate treatments. According to Cruz, diagnosis can take years, which creates enormous uncertainty for families.
"Misdiagnosis or in most cases, late diagnosis,
is a sentence for many of these patients."
Dr. Álvaro Hermida, a specialist in lysosomal diseases, clearly explains thatalpha-mannosidosisis difficult to diagnose, especially in its milder forms, since the symptoms often overlap with those of other, more common conditions. “The disease primarily affects the skeletal, cognitive, and immune systems, but the signs may not be evident until the damage is already very advanced and irreversible,” the doctor notes. Based on his clinical experience, immunodeficiency is one of the earliest symptoms, leading to recurrent infections, especially in the respiratory tract. In addition, many patients develop cognitive difficulties that severely impact their academic performance and adult life.
“A misdiagnosis—or, in most cases, a delayed diagnosis—is a death sentence for many of these patients,” explains Cruz, who recalls how his daughter Sofía was diagnosed withSanFilippo syndrome, another rare lysosomal disorder, before he became fully immersed in the fight for the rights of patients with diseases such as alpha-mannosidosis.
In fact, this was the reason why Jordi today, and for 20 years now, has been raising his voice in this cause. He knows firsthand what it is like to face uncertainty about the future and how it takes hold of families, who must face a long, painful and in many cases extremely costly process in search of answers.
Therefore, when the diagnosis comes late, the consequences for patients are devastating. Life expectancy is drastically reduced, and symptoms progress rapidly since alpha-mannosidosis is a multisystem disease, meaning that it affects several vital organs and functions of the body. As the disease progresses, affected individuals experience cognitive impairment that deprives them of essential skills, such as speech and the ability to learn, as well as suffering from bone deformities, such as scoliosis or joint problems.
“The disease is progressive,” explains Dr. Hermida, “and patients end up becoming completely dependent, although they are very aware of their dependence. And that can be devastating for them.” The deterioration affects not only the body but also the mind, and patients often experience serious psychiatric problems. Without treatment, those affected watch as their world falls apart, with respiratory complications, loss of mobility, and a significantly reduced quality of life.
But the situation can be different if appropriate treatment is started early. Although there is no cure for alpha-mannosidosis,enzyme replacement therapyhas proven effective in slowing the progression of the disease and improving patients’ quality of life. “If treatment is started early, life expectancy can be extended to 50 years,” notes Dr. Hermida, “but if diagnosis is delayed, the damage is already irreversible—especially in the brain—and patients’ life expectancy, as well as their quality of life, is greatly reduced.”
"Despite advances, we are still far from having treatments that cure the disease. We need more research, more resources, and more social support."
The work of patient associations
TheLysosomal MPS Association, led by Jordi Cruz, plays an essential role in supporting families and advocating for improved diagnosis and treatments. Founded in 2003 following the diagnosis of his daughter Sofía, the association has grown exponentially, providing support to more than 1,600 people in Spain living with lysosomal diseases. “Twenty years ago, there were just three of us families searching for answers to our many questions; today, there are more than 600 of us,” Cruz says emotionally. But without a doubt, all the results achieved have been made possible by a tremendous amount of hard work.
Support for families isn’t limited to medical information, which, of course, plays a very important role. Cruz highlights the importance of offeringpsychological support—something that is often overlooked in the treatment of rare diseases and that both doctors and families describe as “indispensable.” “What these families need most is for someone to listen to them and provide answers. They can’t walk alone in this darkness,” she adds. Precisely for this reason, the association also promotes the creation of a support network where those affected can share experiences and resources, creating a space of hope amid the uncertainty that comes with a rare disease diagnosis.
Property of Lysosomal MPS
An optimistic view of the future
Despite advances in diagnosis and treatment, there is still much to be done. Both Álvaro and Jordi emphasize that including lysosomal diseases such as alpha-mannosidosis in universal newborn screening is an urgent priority for addressing treatment. “An early diagnosis could save many lives and improve the quality of life for these patients,” they state. The fact is that, at present, a lack of awareness about these diseases and limited access to diagnostic tests delay clinical intervention:
“Despite the progress made, we are still a long way from having treatments that can cure the disease. We need more research, more resources, and more social support,” the doctor concludes.
The story of alpha-mannosidosis is the story of thousands of families who, day after day, live with a disease that conditions their future, not only that of the patient. With late diagnoses, treatments that, as a consequence, arrive late and a health system that is not yet fully prepared to face the challenge, patients live with the uncertainty of tomorrow.
However, thanks to the efforts of people like Jordi Cruz and professionals like Dr. Álvaro Hermida, there is a beacon of hope. The battle continues, but every advance, every shared story, every voice raised in defense of these patients, is another step towards a better future.
“The system must provide immediate, effective solutions. We must strongly support research and funding for the treatment and diagnosis of rare diseases,” concludes Cruz, in the hope that, one day, no patient with alpha-mannosidosis will have to face the anguish of uncertainty, a delayed diagnosis, and an unknown future.