A female infant was born at 38+ 5/7 weeks gestational age to a 38-year-old mother who had gestational anemia, which was supplemented with oral iron, and gestational diabetes, which was controlled with diet. The mother has a healthy 6-year-old girl but also had a spontaneous abortion and an artificial abortion due to embryo death. The mother's brother had a history of epilepsy and had passed away.
The infant's birth weight, head circumference, and length were 2,830 g (10-25th percentile), 33 cm (25-50th percentile), and 48 cm (10-25th percentile), respectively, with a normal Apgar score. However, she had mild blepharoptosis and there was a 3 cm cleft palate from the palate to the uvula. On day of life (DOL) 2, the infant vomited milk twice accompanied by weakness in sucking. A few hours later, she went into convulsions that involved rowing movements of the limbs. Her blood glucose was 0.7 mmol/L and blood gas analysis revealed anion gap metabolic acidosis (24.69 mmol/L). After providing glucose (8 mg/kg/min) and phenobarbital (10 mg/kg) injection treatment, the convulsions did not occur again, but she became somnolent, developed an unexplained abnormal liver function, and an aggravating increase in serum lactate (16.4 mmol/L). The infant was immediately transferred to our tertiary neonatal intensive care unit (NICU) center on DOL 3 for further newborn care.
The infant's serum lactate was normal on DOL 4 after giving intravenous fluids and nasogastric feeding. Blood glucose was normal on DOL 6 without intravenous fluids. The problems during hospitalization were poor neonatal sucking, reduced movements, and unexplained elevated liver enzymes (gamma-glutamyltransferase (GGT) 1,373 mmol/L, total bile acids (TBA) 58.2 mumol/L, aspartate aminotransferase (AST) 132 U/L,prothrombin time (PT) 46.1s, albumin 26.57 g/L) with normal stool color and abdominal ultrasound. In addition, magnetic resonance imaging (MRI) showed high signals on T2 and FLAIR, where the lenticular nucleus was swollen on both sides. There were multiple hyperintensity patches on the dorsal side of the brainstem and posterior limb of the internal capsule near the anterior and posterior horns of the right lateral ventricle (Figure 1). Evoked otoacoustic emission test was not passed on both ears.
Blood tandem mass spectrometry (MS/MS) showed an increase in tyrosine 227.85 muM (25-225 muM). Urine gas chromatography-mass spectrometry (GC/MS) showed an increase in oxalate 57.78 (0-33), 3-methylglutaconic aciduria 4.35 (0-1), and 3-(4-hydroxyphenyl) lactic acid 1122.49 (0-20). Next-generation sequencing and Sanger sequencing detected two compound heterozygotes of SERAC1 (c.1502-1G>C(likely pathogenic) from the maternal side, c.227-228dupAT(pathogenic) from the paternal side) and a de novo variant of SATB2 (c.1166G>A) (likely pathogenic) (Figure 2). The quality control of WES data analysis and procedure of variant annotation refers to pipeline version 2 of Children's Hospital of Fudan University. We classified the pathogenicity of the identified variants according to the ACMG guideline, the details showed in (Supplementary Table 1).