Child Neurology: Paroxysmal stiffening, upward gaze, and hypotonia

Abstract

Sepiapterin reductase deficiency (SRD) is a dopa-sensitive neurotransmitter disorder, caused by mutation of the SPR gene located on chromosome 2p14-p12.1 To date, 31 patients with 14 mutations have been diagnosed (BIODEF database, update November 2010, www.biopku.org). While classic tetrahydrobiopterin deficiencies present with hyperphenylalaninemia and deficiency of monoamine neurotransmitters, SRD is typically associated with normal phenylalanine levels in blood and pterins in urine2 and not detectable by neonatal screening for phenylketonuria. This implies how important it is to diagnose this condition clinically, in order to provide timely and proper treatment. A summary of the pathophysiology and biochemical pathway is provided by Bonafe et al.2 With the following case report and review of 21 published cases,2,–,10 we elucidate the clinical features of SRD as well as the diagnostic strategy and therapeutic approach. We present a 5-month-old girl, the first and only child born to consanguineous Turkish parents. The parents described the girl's abnormal movements at 3 months of age as sudden stiffening of the whole body, extension of the extremities, upward gaze, and chewing movements lasting for several minutes often after meals, which we also could observe during her hospital stay. Pregnancy and delivery were uneventful. Birthweight, length, and head circumference were within normal ranges. During EEG, a few episodes with chewing movements could be recorded, but no epileptic discharges were evident. The brain MRI was unremarkable. We suspected gastroesophageal reflux and started therapy with omeprazole. The parents reported that the episodes diminished. At 8 months of age, the patient was readmitted because the crises recurred with an increased frequency and duration of up to 25 minutes. During the episodes, the patient revealed circling movements of the hands and rhythmic tremor of the tongue in addition to the previously mentioned symptoms. Remarkably, the …