Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is an ultra-rare kidney disease, with a prevalence of less than one case per million inhabitants. It is a genetic disorder that primarily affects children and young people, characterized by excessive loss of magnesium and calcium in the urine. This imbalance causes nephrocalcinosis, progressive deterioration of kidney function, and in some cases, severe ocular involvement. Currently, there are no specific treatments for this disease, making research essential to understand its mechanisms and develop new therapeutic strategies.

A key alliance to drive pioneering research

In this context, the collaboration between the Vall d’Hebron Research Institute (VHIR) and the Association for Information and Research on Familial Hypomagnesemia (Hipofam) marks ten years since the association’s first financial contribution, a turning point that allowed the launch of a research line that was virtually nonexistent until then. The project was initiated under the leadership of Dr. Anna Meseguer, head of the Renal Pathophysiology Group at VHIR, and Dr. Gema Ariceta, head of the Pediatric Nephrology Service at Vall d’Hebron University Hospital, with the goal of better understanding the disease and improving patient management.

This close alliance between healthcare professionals, researchers, and families has allowed the creation of a solid, long-term project focused on addressing a disease with no specific therapeutic options. “Collaboration with Hipofam has been key to driving research that arises directly from patients’ needs and has a real impact on clinical practice,” emphasizes Dr. Gema Ariceta.

One of the first outcomes of this collaboration was revealing the high phenotypic variability among FHHNC patients. Although in Spain there is a founder mutation, p.G20D in the CLDN19 gene, which means many patients share a common genetic origin, the clinical evolution can differ greatly from one patient to another. “This variability led us to ask a key question: why can patients with the same mutation have such different outcomes?” explains Dr. Anna Meseguer. Based on this question, research projects have focused on identifying the genetic and molecular factors responsible for these differences.

Ten years of scientific progress with translational impact

When this research line began, knowledge about FHHNC was very limited. “When we started, there was practically no structured research on this disease. The continuous support from Hipofam allowed us to launch a project that, ten years later, is producing significant results,” notes Dr. Meseguer. The initial studies focused on analyzing patient biological samples, overcoming important technical challenges thanks to the direct involvement of families and the association.

Over these ten years, collaboration with Hipofam has significantly advanced understanding of the disease. Potential biomarkers, genetic variants that modulate kidney deterioration, and possible therapeutic targets have been identified. “This integrated approach has allowed us to connect molecular data with the clinical progression of patients and advance toward clearly translational research,” notes Dr. Gerard Cantero-Recasens, the group’s principal investigator. Simultaneously, preclinical models, including patient-derived cellular models and animal models, have been developed to study the disease and evaluate new treatments in a controlled environment. This progress has been largely possible thanks to the sustained support of the association, which enabled the hiring of predoctoral research staff over the years. In this context, the contributions of doctoral students such as Dr. Mónica Vall-Palomar, involved in the early stages of the research, and Julieta Torchia, current predoctoral researcher, have been noteworthy. The research line initiated by Dr. Meseguer continues today under the leadership of Dr. Cristina Martínez, principal investigator of the Renal Pathophysiology Group at VHIR, who has taken over scientific coordination. “We have gone from having almost no knowledge about the disease mechanisms to having biomarkers, preclinical models, and potential drugs under study. Researchers and patients have together built a successful collaboration model, with tangible results and a clear future outlook,” emphasizes Dr. Martínez.

Beyond the initial financial support, the close relationship with Hipofam has been crucial to consolidating research and facilitating access to competitive calls that explicitly require collaboration between patient associations and research groups. This alliance model has become an example of how active patient involvement can accelerate scientific knowledge and contribute to improving diagnosis and future therapeutic approaches for rare diseases.

The fundamental role of patient associations in research

For patient associations focused on rare diseases, where knowledge is often limited, and little research is ongoing, the greatest aspiration is to contribute to improving this situation by promoting research. “It is not easy to find a group of researchers interested in studying a rare disease who are also willing to engage with patients. For us, finding the Renal Pathophysiology laboratory team at VHIR was a huge fortune, as it has allowed us to contribute to changing the reality of this disease and dream of finding treatments that substantially improve these children’s quality of life,” says Antonio Cabrera, president of Hipofam. “After ten years, we feel like part of the VHIR team and reinforce even more our commitment to this project and to people with FHHNC. As long as the team continues to have ideas to advance and continue research, Hipofam will be there supporting them and contributing our small part to help. I can only thank them for all the enthusiasm shown, all the work done, all the explanations given, and all the good and difficult moments the team has had over these ten years. Thank you, Gema, Anna, Mónica, Julieta, Gerard, and Cristina, on behalf of all patients with familial hypomagnesemia with hypercalciuria and nephrocalcinosis.”