A Child with Developmental Regression and Electroencephalographic Abnormalities.

Abstract

A 5-year-and-9-month-old boy was referred for investigation of underlying neurometabolic disease. Developmental milestones were normal until 2 years of age when his social and language skills started to regress following a mild infection. He became withdrawn, and stopped speaking and making eye contact. Family history revealed consanguineous parents and a healthy brother. Physical examination was normal except for speech delay, poor social interaction, and poor eye contact, but did not meet the criteria of autism spectrum disorder due to lack of restrictive, repetitive patterns. He did not have clinically evident seizures, but the electroencephalogram showed bilateral frontal and temporal paroxysmal activity that did not resolve with antiepileptic treatment. Brain magnetic resonance imaging was normal. The metabolic workup revealed normal plasma acylcarnitines, moderately increased blood lactate (4.3 mmol/L; reference interval: <2.1), striking increases of proline in plasma (2926 µmol/L; reference interval: 40 to 332) and urine (99 160 nmol/mg creatinine; reference interval: 0 to 250), and urinary 2-ketoglutarate (29 640 mmol/mol creatinine; reference interval: <80) and excretion of pyrrole-2-carboxylglycine (4160 mmol/mol creatinine; not detectable in healthy individuals).