Case Report: Early recognition of neonatal alpha-1 antitrypsin deficiency: a case of subtle presentation and prompt diagnosis

Herein, we present the case of a 4-day-old male infant, born small for gestational age (38 weeks, 2,150 g) to a group B streptococcus-positive mother, admitted with hypothermia, hypoglycemia, and weak cry. Initial evaluation was directed toward neonatal sepsis; however, persistent conjugated hyperbilirubinemia (direct bilirubin peak 2.6 mg/dL; reference <1.0 mg/dL), markedly elevated gamma glutamyl transferase (632 U/L; reference: <70 U/L), and a serum alpha-1 antitrypsin (A1AT) level <20 mg/dL (reference: 100-200 mg/dL) after negative infectious workup prompted metabolic evaluation. The diagnosis of alpha-1 antitrypsin deficiency (PiZZ genotype) was confirmed by the 8th day of life, which is among the earliest reported postnatal diagnoses. An abdominal ultrasound revealed no biliary ductal dilatation but a mildly contracted gallbladder. The condition of the infant improved with supportive management and the patient was discharged with close follow-up with pediatric gastroenterology. This case highlights the importance of considering metabolic and genetic disorders in neonates with persistent conjugated hyperbilirubinemia, particularly after exclusion of infectious causes, and emphasizes that alpha-1 antitrypsin deficiency is not included on routine newborn screening panels.