A Case of Glutaric Aciduria Type II Initially Detected through Newborn Screening in the Philippines

Background: Glutaric aciduria type II (GA II) is an autosomal recessive disorder involving a deficiency in the electron transfer flavoprotein (ETF) and ETF ubiquinone oxidoreductase (ETFQO) which carry electrons to the respiratory chain from multiple FAD-linked dehydrogenases. It is one of the disorders included in the Philippine newborn screening (NBS) panel.

Case Study: The patient is the youngest in a sibship of two, born to a non-consanguineous union of Filipino descent. The older sibling is a confirmed case of GA II initially detected through the Philippine NBS panel. The patient presented with hypoglycemic and apneic episodes on their third day of life (DOL) and was admitted to the neonatal intensive care unit. Given the sibling’s history, he was started on a high dextrose intravenous fluid, Carnitine (200 mg/kg/day), Riboflavin (100 mg/kg/day), and Co-enzyme Q (67 mg/kg/day). The NBS results on the patient’s 4th DOL were consistent with GA II. The plasma acylcarnitine profile showed elevated C4, C5, C5DC, C6, C8, C10, C14, C14:1, and C16. The DNA test revealed a homozygous mutation in the ETFDH gene (p.Gly610Arg). The patient’s condition improved and he was discharged on his 11th DOL.

Discussion: ETFDH variants are commonly associated with late-onset GA II with symptoms presenting from infancy to adulthood. However, this patient presented with symptoms on his 3rd day of life which were associated with elevated acylcarnitines. This case highlights the need to formulate a birthing plan for neonates with siblings confirmed to have a metabolic disorder.

Conclusion: NBS is instrumental in detecting cases of GA II but it is important to also correlate the family history with clinical, biochemical, and DNA test results.