Novel variants in a patient with late-onset hyperprolinemia type II: diagnostic key for status epilepticus and lactic acidosis.

BACKGROUND: Hyperprolinemia type 2 (HPII) is a rare autosomal recessive disorder of the proline metabolism, that affects the ALDH4A1 gene. So far only four different pathogenic mutations are known. The manifestation is mostly in neonatal age, in early infancy or early childhood. CASE PRESENTATION: The 64-years female patient had a long history of abdominal pain, and episode of an acute neuritis. Ten years later she was admitted into the neurological intensive-care-unit with acute abdominal pain, multiple generalized epileptic seizures, a vertical gaze palsy accompanied by extensive lactic acidosis in serum 26.0 mmol/l (reference: 0.55-2.2 mmol/l) and CSF 12.01 mmol/l (reference: 1.12-2.47 mmol/l). Due to repeated epileptic seizures and secondary complications a long-term sedation with a ventilation therapy over 20 days was administered. A diagnostic work-up revealed up to 400-times increased prolin-level in urine CSF and blood. Furthermore, a low vitamin-B6 serum value was found, consistent with a HPII causing secondary pyridoxine deficiency and seizures. The ALDH4A1 gene sequencing confirmed two previously unknown compound heterozygous variants (ALDH4A1 gene (NM_003748.3) Intron 1: c.62 + 1G > A - heterozygous and ALDH4A1 gene (NM_003748.3) Exon 5 c.349G > C, p.(Asp117His) - heterozygous). Under high-dose vitamin-B6 therapy no further seizures occurred. CONCLUSION: We describe two novel ALDH4A1-variants in an adult patient with hyperprolinemia type II causing secondary pyridoxine deficiency and seizures. Severe and potentially life-threatening course of this treatable disease emphasizes the importance of diagnostic vigilance and thorough laboratory work-up including gene analysis even in cases with atypical late manifestation.

A novel method of eliciting pain-related potentials by transcutaneous electrical stimulation.

BACKGROUND: Electrophysiological techniques such as laser and contact heat evoked pain-related potentials are very useful for studying trigeminal and somatic pain transmission in humans. These methods are, however, partly invasive, expensive, and therefore not available for broad clinical use. We recently proposed a novel technique of noninvasive transcutaneous electrical stimulation. OBJECTIVE: To elicit pain-related evoked potentials (PREP) by using a concentric planar electrode and demonstrate their nociceptive specificity. METHODS: We registered PREP following stimulation of the forehead and hand in 14 healthy volunteers. Latencies, peak-to-peak amplitudes, and conduction velocities of nociceptive fibers have been estimated. Effects of temporal and spatial summation and of cutaneous anesthesia were evaluated. RESULTS: Stimulation with the concentric planar electrode produced pinprick-like painful sensation. Cutaneous anesthesia led to abolishment of PREP responses. Estimated mean conduction velocity was 11.61 +/- 5.12 m/s, which corresponded well with conduction via A-delta fibers. Spatial as well as temporal summation resulted in a parallel increase of perceived pain intensity and PREP amplitudes. CONCLUSION: The technique is noninvasive, affordable, and easy to perform and allows quantitative assessment of human nociceptive pathways.