In the past decade, the number of medical conditions for which newborns are universally screened has greatly expanded, due in part to recommendations from the Maternal and Child Health Bureau. The Bureau’s expert panel called for screening of a core set of 29 conditions and also suggested 25 additional conditions be reported to families, although accepted treatments are not yet available. It is the second part of this recommendation which touched off an old debate: If there is no accepted treatment for a condition, should there be mandatory screening? Proponents of expanded screening argue there are benefits to families and societies of knowing conditions exist, even if treatments are not yet available. This paper looks back at the experience with mandatory newborn screening (NBS) for histidinemia and finds a cautionary tale for today.

Key Findings:

• Histidinemia is a disorder of amino acid metabolism similar to phenylketonuria and in the 1960s was thought to be linked to intellectual disability. By the early 1980s, the consensus was that histidinemia was a normal variant, with treatment and screening unnecessary. NBS was never “unequivocally” recommended.
• Millions of children were screened for histidinemia as part of state NBS programs from the 1970s through the 1990s. Some were treated with restricted diets, subjecting both themselves and their families to the stress of dietary control, regular blood draws and uncertainty about the future.

The authors argue decisions regarding NBS are influenced by the times in which they are made. In the case of histidinemia, the U.S. was focused on the prevention, as well as social and personal costs, of intellectual disabilities due to numerous political factors. The authors also assert that U.S. medicine, then and now, is based on the belief that the key to improving health is the “application of technologic advances that prevent or treat illnesses” and this “may lead us, almost reflexively, to overestimate the value of expanding NBS programs.” But experience with histidinemia also demonstrates there may be valid public health reasons to include certain conditions in NBS solely for the purpose of research and without recommending treatment. Having a record of the natural history and variants of a condition is valuable to understanding it and, for rare conditions, this may only be obtained through screening large populations.

Thus, the case of histidinemia provides evidence of why mandatory screening is potentially valuable and why treatments should not be too hastily implemented. The authors note, however, there will be a need for innovative models of informed consent to carry out such research through NBS.