Hundreds of thousands of children are born each year with a metabolic disorder and others surface during the earliest days of life and into young childhood. When detected early, many life threatening metabolic deficiencies in infants and children may be corrected by diet or with existing and emerging therapies. Initiating precise management at a young age reduces a child’s lifelong complications.

The Metabolic Health Center is founded on the notion that metabolic profiling has the potential to detect health problems earlier than ever before possible and with a greater level of precision thanks to modern technologies. We believe metabolic phenotyping will provide mechanistic insight into human development and disease and suggest treatment strategies.

Our vision of precision health through metabolomics in neonates and children is “Cure through Prevention

Since metabolism is a significant contributor to most human diseases, it manifests in both acquired and inherited (genetic) diseases. Overall, neonatal conditions account for 9% of worldwide disease burden. Around the globe, millions of babies are born either too soon or too small. In the developing world, this is often the result of chronic under-nutrition or malnutrition, whereas in industrialized countries, the problem presents as prematurity. Abnormal metabolism is associated with and a possible significant contributor to acquired diseases of newborns who are born premature, (e.g. neurodevelopmental impairment of the brain, retinopathy or prematurity, respiratory distress or lung disease, necrotizing enterocolitis, sepsis.) Examples of genetic diseases that affect metabolism evident at birth include Phenylketonuria (PKU) and Maple syrup urine disease (MSUD), Niemann-Pick disease, and more than a thousand other types of disorders. If these diverse conditions are not recognized early, children often suffer with progressive liver/brain damage, coma, and other life-threatening complications. Metabolic diseases that usually appear during childhood include diabetes and dyslipidemia, (or abnormal lipid accumulation leading to additional diseases of the heart and blood vessels among others).

The California newborn screening program covers approximately 40 different metabolic diseases through multiple individual and time-consuming assays. By restricting the search space to a limited number of metabolites that are already known to cause disease, many more personal metabolic abnormalities are missed and go untreated, resulting in as much as 40% of children with special needs remaining undiagnosed. Additionally, by focusing solely on genetic metabolic disorders in newborn screenings, we are missing an opportunity to study common pathways of acquired metabolic diseases, like prematurity or diabetes.

Profiling children and newborns will allow us to:

  1. Identify specific metabolome patterns associated with human disease (e.g. prematurity, diabetes) on a level that has never been done before
  2. Establish profiles that match to existing human disease (diagnostic), or risk of acquiring disease (surveillance, prognostic)
  3. Link to genome/exome sequences to better understand genetic basis of disease
  4. Identify metabolic pathways of disease; develop clinically-validated assays and assess therapeutic targeting or prevention

Over the past several years, there have been significant advances in mass spectrometry that enable expeditious determination of a person’s global metabolic profile and detection of a wide range of metabolic diseases as a result. These technologies, many of which were developed at Stanford as well as employing technology from Thermo Fisher, can be used to rapidly pinpoint problems for the child, often before symptoms arise. We will be able to more broadly identify the cause of many diseases and in some cases suggest treatments. Mass  spectrometry will serve as a valuable resource for both scientific and clinical application.

We have established the Metabolic Health Center as part of Maternal and Child Health with the goal of improving the metabolic health of every child born or admitted at Stanford. We will begin by analyzing 1000 neonates and children.  The center will ultimately profile every child that is born at Lucile Packard Children’s Hospital Stanford as well as older children that enter the hospital and other Stanford Children’s Health clinics. Our aim is to keep children healthy, rather than treat them after they get disease.