Researchers in study validate test to identify newborns with homocystinuria, a rare inherited disease

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Researchers in a study have evaluated a test that provides early detection for infants with homocystinuria (HCU) -- a rare inherited disease that, if not treated early, causes serious complications.

Research demonstrating the efficacy of the test was published Wednesday in Clinical Chemistry.

HCU impedes an infant’s ability to metabolize the amino acid methionine, a component of many proteins, including those found in breast milk. This leads to a pathological increase in the methionine levels, in addition to raising the levels of another amino acid called homocysteine, causing severe complications if left untreated. These complications range from eye and skeletal issues to vascular abnormalities and intellectual disabilities. Early HCU detection and treatment can prevent these complications.

Since 2006, the U.S. Department of Health and Human Services has included HCU on the list of disorders for which newborns should be screened. However, current tests only measure methionine levels, which are often still low when newborn screening occurs. As a result, these tests may miss an estimated 50% of HCU cases, which are then at high risk of being left untreated.

In order to remedy this situation, the researchers developed a newborn screening test for HCU that measures homocysteine levels. In infants with HCU, homocysteine levels usually rise before methionine levels. They almost always rise during the first few days of life -- the time when newborn screenings are usually performed -- making homocysteine a better early marker of this disease.

To evaluate the test’s performance, the team used it to screen dried blood spot extracts and residual clinical specimens from infants who had already received diagnoses. One hundred of these samples came from infants presumed healthy. Fifty samples came from HCU-negative infants receiving total parenteral nutrition -- intravenous feeding of specialized liquid food -- which is given to premature babies in neonatal intensive care units. Two samples were from HCU-positive infants.

The test distinguished between healthy and HCU-positive samples based on homocysteine levels. It also accurately classified the samples from newborns receiving total parenteral nutrition as HCU-negative, the researchers said.

They considered this noteworthy because methionine tests for HCU are known to produce problematic false positives in babies receiving intravenous nutrition.

“Here we present the only flow injection analysis–tandem mass spectrometry first-tier newborn screening method that directly quantifies total homocysteine from dried blood spots,” explained co-author Konstantinos Petritis, laboratory chief at the Centers for Disease Control and Prevention, in a statement. “The ability to screen total homocysteine during first-tier newborn screening is a significant step toward reducing HCU false-negative rates, which will enable early identification and intervention to reduce HCU-associated morbidity and mortality.”

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