L-Serine Biosynthesis Defect: A Treatable Condition Masquerading as TORCH Infection

To the Editor: 3-Phosphoglycerate dehydrogenase deficiency (PHGDHD) is a defect in the L-serine biosynthesis pathway and presents with developmental delay, seizures, cataract, and microcephaly [1]. Here we report a child with a novel splice variant in PHGDH gene with infantile onset serine deficiency. A 23-mo-old boy presented with developmental delay, refractory polymorphic seizures, and spasticity. Antenatal scans had shown intrauterine growth retardation with microcephaly. The child was born full term with birth weight of 2.2 kg and was operated for bilateral cataract at 5th mo of life. Developmentally, he had not attained neck control and social smile. On examination, microcephaly (head size: 37 cm, < -3 SD), weight (7.5 kg, < 3rd centile), length (72 cm, < 3rd centile), large low set ears, syndactyly of the 3rd and 4th toes of both feet, nystagmus, optic atrophy, spasticity, dystonia, and extensor plantar response were noted. Complete hemogram, liver and renal function, serum ammonia and lactate, and tandem mass spectrometry were normal. TORCH serology was negative. EEG showed multifocal epileptiform discharges. MRI brain showed ventriculomegaly, cerebral atrophy, and thinning of corpus callosum. CSF amino-acid analysis showed low serine: 11 µmol/L (normal- 26–63 µmol/L). Exome sequencing showed a novel homozygous splice site variant c.411+5G>C, p.(?) in intron-4 of PHGDH gene classified as variant of unknown significance as per ACMG classification [2]. After treatment with L-serine (300 mg/kg/d) in four divided dosages, seizure frequency decreased and improvement in the development in the form of head control, and eye contact were noted. …