LAUSR

A 6-month-old male presented to the emergency department during the COVID-19 pandemic with 3-day history of fever, nasal congestion, cough, and decreased oral intake. He was not able to sit with support or roll over, and his growth parameters were severely reduced (<1st percentile). He tested negative for COVID-19, and had an unrevealing newborn screen. Severe failure to thrive (FTT) had been evident since his well-child visit at age 2 months. The family was instructed to increase his caloric intake. At the 6 months visit, he was found to have only gained 1 kg since birth and was febrile, prompting emergency department referral. Initial workup was notable for increased aspartate aminotransferase [567 U/L, reference interval (RI): 20– 64 U/L] and alanine aminotransferase (210 U/L, RI: 5– 45 U/L), decreased normal total protein (5.6 g/dL, RI: 5.4–7.0 g/dL) and albumin (3.5 g/dL, RI: 3.1–4.2 g/dL), and low thyroid-stimulating hormone (0.22 mIU/ml, RI: 0.70–4.20 mIU/mL) and free thyroxine (0.5 ng/dl, RI: 1.0–1.8 ng/dL). His chest radiograph showed cardiomegaly, and echocardiogram identified a large globally distributed pericardial effusion associated with normal ventricular function. Genetic and metabolism services were consulted for FTT and developmental delay. Hypotonia, poor head control, intermittent esotropia, inverted nipples, bilateral undescended testes, and suprapubic and lateral gluteal fat pads were noted, suggesting a congenital disorder of glycosylation (CDG). Carbohydratedeficient transferrin analysis revealed a type-I pattern, with profoundly increased hypoglycosylated transferrin glycoforms (Fig. 1, A). Total plasma N-glycan analysis revealed remarkable undermannosylation, with increased mannose-deprived tetrasaccharide and Man0–5GlcNAc2, and reduced Man8–9GlcNAc2 (Fig. 1, B). The biochemical and clinical findings were consistent with phosphomannomutase 2 congenital disorder of glycosylation (PMM2-CDG), confirmed by compound heterozygous pathogenic variants in PMM2: c.368G>A (p.Arg123Gln) and c.691G>A (p.Val231Met). Unfortunately, the patient’s clinical status deteriorated, and he died due to bleeding complications during attempts to surgically address his pericardial effusion.