Bridging the Gap: How Proteomics Solves Diagnostic Mysteries in Rare Pediatric Diseases

When a child's vision slips away from a rare inherited disorder, we face a clinical moment that pushes every immunologist and geneticist to the edge of what we currently know how to treat. As CNBC reports, an experimental gene therapy exists that could halt that progression — yet getting it into the patient's hands is the hard part. For our community, the story is less about a single disease and more about a pattern we keep meeting in clinic: a child with progressive symptoms, a long diagnostic odyssey, and a treatment that is technically possible but practically out of reach.

Where diagnostics still fail our patients

We know how much ground genome sequencing has covered, especially through programs like Genomics England's 100,000 Genomes Project. But a meaningful slice of children and families still walk away without a definitive molecular answer. According to Medical Xpress, researchers from Queen Mary University of London, the Berlin Institute of Health at Charité, and Genomics England have now shown that measuring nearly 1,500 proteins in blood, layered onto existing genomic data, can resolve some of those lingering uncertainties.

What makes this relevant for us is the focus on variants of uncertain significance, or VUS — the genetic changes we find but cannot yet call pathogenic. Dr. Julia Carrasco-Zanini, first author from Queen Mary's Precision Healthcare University Research Institute, noted that genome sequencing has transformed diagnosis but still leaves many patients without an answer, and that unusually low or high protein levels can serve as a functional readout of whether a variant is truly disrupting gene function. In other words, proteomics can tell us whether the biology matches the genetics. The team found this combined approach especially helpful in patients with hereditary hemorrhagic telangiectasia, a rare vascular disorder, but the principle travels: functional protein evidence may sharpen interpretation of VUS in primary immunodeficiencies as well.

A gene therapy for the eyes — and the questions it raises

Alongside the diagnostic story, BioWorld reports progress with Opus's BEST1-targeted gene therapy in rare inherited eye diseases. For pediatric immunologists and our colleagues in genetics, BEST1-related retinal dystrophies are a reminder that several of the rare conditions we co-manage — those affecting vision, vasculature, and connective tissue — are now sitting at the threshold of single-gene curative approaches.

That is the hopeful part. The harder part, which the CNBC piece underscores, is access. Even when a biologic mechanism is sound and a trial reads out well, reimbursement, manufacturing capacity, infusion-center readiness, and post-treatment immune monitoring can determine whether a family ever sees benefit. We should be asking, alongside regulatory and payer questions: who will follow these patients long term for immune reactions, vector-related events, or durability of effect?

What we should be doing now in clinic

For clinicians advising a family today, three practical points are worth carrying forward. First, when a child with a suspected rare disease carries a VUS, ask whether functional data — including emerging proteomic readouts — can be incorporated before closing the diagnostic file. Second, for any family where a one-time gene therapy is on the table, build the access conversation early: eligibility criteria, geographic logistics, insurance pre-authorization, and the immune-surveillance plan that follows infusion. Third, keep the multidisciplinary channel open between immunology, genetics, and ophthalmology; rare disease care rarely lives in one specialty.

We are watching a field where the science is moving faster than the systems meant to deliver it. For our patients, that gap — between what we can explain and what we can offer — is where our attention most needs to stay.