P2.244: Phenylketonuria in a Preterm Infant Complicated by Necrotizing Enterocolitis

Introduction: Phenylketonuria (PKU) is a rare autosomal recessive metabolic disorder caused by a deficiency of phenylalanine hydroxylase, leading to elevated phenylalanine levels and neurodevelopmental impairment if untreated. Management in preterm infants is particularly challenging due to metabolic immaturity and nutritional constraints. Here, we present a unique case of a 27-week preterm infant diagnosed with PKU who subsequently developed necrotizing enterocolitis (NEC), leading to significant clinical deterioration.

Case Description: A male infant was born at 27 weeks and 2 days gestation (birth weight: 920g, 37th percentile) via cesarean section due to HELLP syndrome with fetal malpresentation. Resuscitation included positive pressure ventilation for two minutes, and the infant was stabilized on CPAP. Initial metabolic screening revealed hyperphenylalaninemia, which was later confirmed by molecular testing as mild PKU. Given prematurity and feeding intolerance, nutrition was initially managed with parenteral nutrition (PN), with cautious introduction of a phenylalanine-restricted enteral diet.

At postnatal day 42, the infant developed abdominal distension and hemodynamic instability, with radiographic findings concerning for pneumatosis. He underwent emergent laparotomy, which revealed extensive bowel necrosis necessitating resection of 37.5 cm of the small intestine and ascending colon. Pathology confirmed transmural necrosis with inflammatory exudates. The post-operative course was complicated by feeding intolerance, recurrent bacteremia, worsening metabolic instability, and progressive malnutrition despite careful adjustments in PN and enteral feeding strategies. Dermatologic complications, including desquamating skin lesions, were later attributed to zinc deficiency.

Discussion: Challenges in PKU Management and Outcomes
The coexistence of PKU and NEC introduced significant challenges in metabolic and nutritional management. Prematurity alone complicates amino acid metabolism, and the additional burden of intestinal resection further impaired phenylalanine regulation, leading to erratic plasma levels. Standard PKU management with phenylalanine-free amino acid solutions was limited by ongoing gastrointestinal dysfunction, necessitating prolonged PN, which carried additional risks of cholestasis and micronutrient deficiencies. The need for aggressive nutritional rehabilitation while preventing phenylalanine toxicity or deficiency required continuous metabolic monitoring and individualized dietary modifications.

Further, the patient experienced prolonged systemic inflammation secondary to NEC, recurrent sepsis, and chronic TPN dependency, all of which likely contributed to altered protein metabolism and growth failure. Despite extensive interventions, the transition to full enteral feeds remained difficult, raising concerns about long-term intestinal adaptation. This case underscores the need for a multidisciplinary approach to optimize nutrition in complex preterm infants with metabolic and gastrointestinal disorders.

Conclusion: This case highlights the complexities of managing PKU in preterm infants, particularly when complicated by NEC and subsequent intestinal failure. It underscores the need for tailored nutritional strategies that account for both metabolic and gastrointestinal complications. Further research is needed to guide optimal nutritional interventions in this vulnerable population.