Advancing Newborn Screening for Rare Metabolic Disorders: Innovative Diagnostics for CACT Deficiency

Jose Luis Chiara.

Agencia Estatal Consejo Superior de Investigaciones Científicas, M.P., Spain.

CACT deficiency is a rare metabolic disorder that causes severe, life-threatening symptoms in newborns. Without rapid intervention, the prognosis is very poor. Current screening methods identify abnormal metabolic patterns but cannot confirm the condition quickly enough, delaying treatment and increasing the risk of serious complications or death. This project aims to develop a new diagnostic test that can confirm CACT deficiency quickly and accurately.

The assay is based on a selective substrate probe for CACT and measures transporter activity directly in patient-derived live cells. The test produces a quantitative readout within one day, is technically simple, cost-effective and compatible with existing newborn-screening workflows, making it suitable for widespread use. The team aims to validate the assay in clinical settings and assess its integration into newborn screening programmes.

By avoiding delays, the test could improve diagnosis and treatment of CACT deficiency. This would help prevent irreversible damage, improve outcomes and reduce intensive-care costs. The test may also have applications in oncology, as low CACT expression has been associated with poor survival in multiple cancers.

• Maria Dolores Chiara Romero, Fundación para la Investigación e Innovación Biosanitaria en el Principado de Asturias, Spain.

• Virginia Martinez Martinez, Universidad del Pais Vasco (UPV/EHU), Spain.

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