Further delineation of the phenotypic and metabolomic profile of ALDH1L2-related neurodevelopmental disorder.

ALDH1L2, a mitochondrial enzyme in folate metabolism, converts 10-formyl-THF (10-formyltetrahydrofolate) to THF (tetrahydrofolate) and CO2. At the cellular level, deficiency of this NADP+-dependent reaction results in marked reduction in NADPH/NADP+ ratio and reduced mitochondrial ATP. Thus far, a single patient with biallelic ALDH1L2 variants and the phenotype of a neurodevelopmental disorder has been reported. Here, we describe another patient with a neurodevelopmental disorder associated with a novel homozygous missense variant in ALDH1L2, Pro133His. The variant caused marked reduction in the ALDH1L2 enzyme activity in skin fibroblasts derived from the patient as probed by 10-FDDF, a stable synthetic analog of 10-formyl-THF. Additional associated abnormalities in these fibroblasts include reduced NADPH/NADP+ ratio and pool of mitochondrial ATP, upregulated autophagy and dramatically altered metabolomic profile. Overall, our study further supports a link between ALDH1L2 deficiency and abnormal neurodevelopment in humans.

Treatment of plane warts with long pulse ND - YAG laser 532 nm.

BACKGROUND: Warts are one of the contagious viral diseases that may cause disturbing cosmetic problems. Plane warts represents a common self-limiting viral infection of the skin caused by the Human Papilloma Virus, however, those that do not disappear by themselves can be very difficult to treat with no uniformly effective treatment modality. OBJECTIVE: To assess the efficacy of long pulsed 532 nm ND:YAG  laser in the treatment of plane warts. PATIENTS AND METHODS: In this therapeutic clinical trial study, 34 patients with plane warts were enrolled. Each patient was eligible for up to three treatment sessions administrated at 2 weeks intervals with long pulsed ND:YAG  laser at a spot size 3 mm; wavelength 532 nm; pulsed duration 20 ms; and fluence 30 J/cm2 . The patients were assessed before each treatment session and at 3 months after the last treatment session. The response to treatment was graded using four points scale: Scale 1 = poor: <25%, Scale 2 = fair: 25%-50%, Scale 3 = good: 51%-75%, Scale 4 = excellent: >75%. RESULTS: Twenty-two patients only with a total of 478 lesions, completed the study; their ages ranged from (6-45) years with a mean ± SD 19.95 ± 13.142 years. Thirteen patients (59.09%) were female and nine (40.90%) were male. The results from this study showing that long pulsed ND:YAG laser 532 nm led to an excellent response in 19 patients (86.36%) in which 15 of 19 patients showed a complete response (78.94%); one patient showed a good response (4.545%), one showed a fair response (4.545%) and one showed a poor response (4.545%) at the end of three-months follow up. The difference was statistically significant; the P value at the three months follow-up was 0.002. The cumulative clearance rate after the first, second, and third treatment sessions was 58.4%, 77.7%, and 89.9% respectively. Recurrence was seen in only one patient (4.545%). Side effects were generally mild and didn't prevent normal activity. CONCLUSION: Long pulsed ND:YAG laser 532 nm appears to be an effective method for treatment of plane warts.