In an article being early released this week in Pediatrics, Dr. Ulrike Mutze, MD, Julia Stengel, and colleagues at Heidelberg University and other institutions in Germany describe a prospective observational study of 257 German children who had been diagnosed with a metabolic disease through newborn metabolic screening with tandem mass spectrometry (10.1542/peds.2024-068293). The children were followed for 15 years (from preschool to adolescence) to examine the effectiveness of tandem mass spectrometry in the newborn period to diagnose metabolic disease.
The good news is that the majority (70.1%) of children did not develop any observable permanent disease associated with their underlying metabolic disorder. However, almost half (44.8%) experienced a metabolic decompensation and hospitalization, and over 10% had a decompensation prior to the newborn screening results being available.
Overall, the observed impact of the underlying metabolic disorder on various outcomes (intelligence quotient [IQ], decompensations, and hospitalizations) is consistent with conventional wisdom. Nearly 85% of participants were on some form of therapy, and those who adhered to therapy were less likely to have disease-associated symptoms and associated metabolic decompensations.
Certain subgroups (those with phenylketonuria, biotinidase deficiency, attenuated isovaleric aciduria, or attenuated very long-chain acyl-CoA dehydrogenase deficiency) were less likely to have associated decompensations requiring hospitalization. Similarly, there were certain groups (including those with phenylketonuria and medium chain acyl-CoA dehydrogenase deficiency) who infrequently displayed phenotypic symptoms of their underlying metabolic disease. Overall, the observed metabolic decompensations and associated hospitalizations decreased as the participants aged.
Over 80% of participants had a global IQ at or above the 85th percentile and, as would be expected, those who showed no symptoms of their underlying disorder had higher IQ scores. Most children (91%) attended a mainstream classroom.
The authors correctly outline the known benefits of newborn metabolic screening as it relates to mitigating disorder-related morbidity and mortality. They also highlight the limitations of the study, including the small sample size and the difficulty of extrapolating these findings to other settings where the availability of treatment may be tenuous. Even in places that have been at the forefront of the identification and treatment of these disorders, changes in political priorities and associated funding can have profound impact on children born with such disorders.
This article reminds us of the importance of having continuous and sustained funding for programs like Medicaid that provide needed resources for children born with metabolic disorders—particularly as new (and sometimes prohibitively expensive) therapeutics are available, increasing the pressure to add more disorders to the newborn screen.
