The Importance of Early Diagnosis of Genetic Illness in Neonates 

Most individuals are familiar with critically ill newborn cases. The kids that make the adrenalin surge and keep us up at night. Perhaps their pregnancies were normal. Or, perhaps there were one or two signs of trouble, but not enough to cross over the threshold for needing prenatal testing. Sometimes, their labor and birth are completely normal, but that could also be when things started to go awry. As soon as the baby is born, everyone unconsciously holds their breath until its cry is heard. The newborn cry from the trauma of birth into this bizarre new world signals to those present that she or he is breathing.

However, after evaluation it becomes apparent that the baby’s Apgar scores are low. Instead of a healthy score of 10 and 10, the combined total is less than ideal, and the baby’s first few minutes are not going as planned. The parents sense things are not normal.

Although this has not been vocalized, the medical team of midwives and doctors are able to communicate the urgency of the situation with their actions. The neonatologist is paged. The pediatrician performs examinations and administers medication. Instead of resting on mom’s chest, the baby is about to be taken to the NICU. Vital signs are weak, breathing is labored, the baby is sick and not feeding. Blood is taken and the routine tests are abnormal. Then, the next round of tests have abnormal results too with various levels outside the expected range. Muscle tone is low. Is the baby a little dysmorphic, too?

Shortly after, the baby is referred for an inpatient genetics consult. A clinical geneticist and genetic counselor meet with the parents. It was not that long ago that clinical genetics was more of an afterthought. Previously, clinical genetics was seen as more appropriate for the outpatient clinic after meeting with other specialists. Now, as medicine evolves, genetics is at the forefront of the clinicians’ minds. The importance of having a diagnosis early on can alter the management and treatment of a patient. A timely genetic diagnosis has the potential to save lives.

The clinical geneticist and genetic counselor consult with the parents and recommend a Critical Trio Whole Exome Sequencing (WES) test. After receiving consent from the parents, the physician also ordercomplementary tests for WES: Chromosomal Microarray Analysis (CMA) and Global Metabolomic Assisted Pathway Screen (Global MAPSTM ), a metabolomic screening test.  

The geneticist and genetic counselor explain that these tests are critical to knowing the underlying issues that are shown in the baby. After 14 days, the results for CMA were normal. However, the Critical Trio WES test identified a pathogenic variant in one allele and a variant of unknown significance (VUS) in the other allele of an inborn error of metabolism gene. The infant had inherited one variant from the mother and the other variant from the father.  

 A week later, the specialists receive the results of the Global MAPSTM test – it’s abnormal. For the gene in which two variants were identified by WES, Global MAPSTM  shows abnormalities in the protein coded region of that gene. Using this data, the laboratory was able to reclassify the VUS as likely pathogenic.  

What do these results mean for this newborn? The specialists were able to tailor medical management and treatment of the baby with a daily vitamin supplementLuckily, the baby has a great prognosis. Reproductive options are available for the newborn’s parents and carrier testing is available for the extended family. 
For rare disease diagnosis in critically ill newborns, BG offers:  

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