8 September 2023

Newborn Screening (NBS) is a routine and critical part of newborn primary care healthcare in Washington State. It is a very effective way to prevent infantile death due to inborn or acquired errors of metabolism. The testing occurs twice during a very important time in a newborn’s life: Washington State law requires that a first NBS is to be done within the 48 hours of life, and it is standard of care for a second NBS to occur at day 7-10 of life. It is estimated that 84,000 newborn tests are completed annually in Washington State. Through NBS testing, the state is able to quantify about 200 infants per year with an identifiable metabolic disorder and about 1300 infants with a hemoglobin trait. Certain groups that are not captured in these numbers are some out of hospital births, declined tests, or other situations. After a confirmed diagnosis, the NBS team at the state level help to make sure the baby is linked into specialty care through its partners: Seattle Children’s, Mary Bridge, Northwest Sickle Cell Collaborative, or University of Washington, to name a few.

The Technical Advisory Committee (TAC) to the Washington State Department of Health (DOH) Newborn Screening Panel reviews available evidence and recommends inclusion consideration to the Washington State Board of Health based on 3 main guiding principles: (1) recommendations are driven by evidence, (2) recommendations are accessible, and (3) the benefits outweigh the harms. The Board of Health ultimately decides which newborn screening panels to include but considers the TAC’s recommendation when making its decision. Each condition to be reviewed must also fit certain NBS criteria regarding laboratory testing, diagnostic testing, treatments available if a condition is detected, prevention for potential harm, medical rationale, public health rationale, as well as cost-benefit and cost-effectiveness outcomes.

This was my fourth experience serving on the TAC for the Washington State NBS Panel. In previous years that I have been on the panel, we have reviewed Spinal Muscular Atrophy (SMA), Ornithine Transcarbamylase Deficiency (OTCD), and congenital cytomegalovirus (cCMV). The panel currently has 32 conditions tested, with the most recent addition of Spinal Muscular Atrophy (SMA) in 2020. The panel met on 8 September 2023 to discuss the addition of Guanidinoacetate methyltransferase (GAMT) deficiency and Arginase 1 deficiency (ARG1-D) to the Washington State newborn screening panel.

Briefly, GAMT deficiency is a rare autosomal recessive genetic disorder that is one of three inborn errors of creatine metabolism and transport. There are about 130 individuals worldwide with this condition. Without this genetic disorder, when we have protein intake, arginine and glycine are broken down by the arginine:glycine amindinotransferase enzyme into ornithine and guanidinoacetate (GUAC), respectively. GUAC is a neurotoxic metabolite from this biochemical process. GUAC is then typically changed into creatine by guanidinoacetate methyltransferase (GAMT) and further into creatinine for use by brain and muscles. When GAMT is not working well, GUAC rises in blood levels and creatine is low in both blood and urine. Symptoms become recognizable between 3 months to 2 years of age for the child, depending on access to care. Typical symptoms include developmental delays, cognitive impairments, speech/language delays, variable behavioral issues (including hyperactivity and autism), epilepsy, movement disorders, and hypotonia. Molecular genetic testing tests for the GAMT gene and confirms diagnosis. The mainstay of treatment for this condition includes oral creatinine supplementation at high levels to replenish cerebral creatinine stores, as well as dietary modifications, additional supplements if needed, monitoring of labs, and additional supports of PT/OT/speech specialists for those individuals with GAMT deficiency.

ARG1-D is also a rare autosomal recessive condition, with about 260 individuals identified worldwide. This is also a condition of urea cycle disorder, but is distinct from others with elevated arginine levels, compared to hyperammonemia. ARG1-D is asymptomatic during infancy and childhood when the most damage occurs to the central nervous system. Typically symptoms arise between 1-3 years of age, characterized by progressive spastic diplegia, more often in the lower extremities, which affects an individual’s ability to ambulate. This condition is often misdiagnosed as cerebral palsy, even if the birth or clinical history does not fit. Other symptoms that are part of this condition include cognitive delays, loss of milestones, seizures, growth failure, microcephaly, feeding difficulties, intermittent hyperammonemia with illness or stress, and intermittent liver dysfunction. Typically labs for plasma arginine levels are elevated and genetic testing of ARG1 gene is diagnostic. The focus of treatment for this condition is to reduce arginine levels through dietary restriction, supplementation with arginine-free essential amino acid formula, and ammonia diversion therapy through medications. Symptomatic management may also include Neurology, Rehab, PT/OT/Speech specialists as needed.

As I have mentioned in previous updates from the NBS TAC, the most important take away from meetings like this are the implications of public health and the importance of mass screening vs. risk-based screening. To look at this from a lens of risk-based screening is difficult because often times, these conditions occur without prior family history or indications. No test is 100% fool proof. Very few tests are 100% sensitive or specific. However, public health and medical cost implications are clear and certain steps can be taken toward prevention of these diseases and morbidity associated in some, during a very pivotal time in a child’s healthcare journey.

Knowledge is power and, in certain situations, more information may give us just the edge that we need to overcome a challenge and/or to think more clearly about a medical condition. As a parent, I can identify with wanting to know the facts and wanting all the information to make a fully informed decision. As a physician, I can identify with both wanting to do the best thing for a family in office as well as for public health at large. NBS gives an opportunity to help families get answers that may otherwise not be available to them. This advisory committee worked hard to weigh the evidence to ultimately made the recommendation to the Board to consider adding GAMT deficiency and ARG1-D to the NBS panel for Washington State.

The Washington State Board of Health will meet on October 9, 2023. At that meeting, the NBS panel staff will present an overview of committee discussions and final recommendations to the Board. This meeting will be open to the public for those interested in wanting to watch the discussion and deliberation, and see the TAC’s recommendation of adding the GAMT and ARG1-D screening tests. If passed, I look forward to being able to say that I helped make a recommendation to expand the 32 diseases on the NBS in Washington State for future infants and their families. I whole-heartedly love representing the WANP members on this TAC for NBS and look forward to future opportunities to help improve newborn screening care in our state.

~Krystal Plonski, ND, LAc, FABNP | WANP Liaison to TAC for DOH NBS Panel