NANS-CDG is a congenital disorder of glycosylation (CDG) caused by biallelic variants in NANS, encoding an essential enzyme in de novo sialic acid synthesis. It presents with intellectual developmental disorder (IDD), skeletal dysplasia, neurologic impairment, and gastrointestinal dysfunction. Some patients suffer progressive intellectual neurologic deterioration (PIND), emphasizing the need for a therapy. In a previous study, sialic acid supplementation in knockout nansa zebrafish partially rescued skeletal abnormalities. Here, we performed the first in-human pre- and postnatal sialic-acid study in NANS-CDG. In this open-label observational study, 5 patients with NANS-CDG (range 0-28 years) were treated with oral sialic acid for 15 months. The primary outcome was safety. Secondary outcomes were psychomotor/cognitive testing, height and weight, seizure control, bone health, gastrointestinal symptoms, and biochemical and hematological parameters. Sialic acid was well tolerated. In postnatally treated patients, there was no significant improvement. For the prenatally treated patient, psychomotor and neurologic development was better than two other genotypically identical patients (one treated postnatally, one untreated). The effect of sialic acid treatment may depend on the timing, with prenatal treatment potentially benefiting neurodevelopmental outcomes. Evidence is limited, however, and longer-term follow-up in a larger number of prenatally treated patients is required.

UNASSIGNED: To verify the effects of multi-domain computerized cognitive training on intellectual function and adaptive functioning in children with intellectual developmental disorder (IDD).
UNASSIGNED: Children with IDD were randomized to a multi-domain computerized cognitive training (CCT) group (n = 30) and control group (n = 30). Both groups received a 5-week training program. Intellectual function was assessed by Chinese-Wechsler Young Children scale (C-WYCSI) and adaptive functioning was assessed by the Chinese Vineland Adaptive Behavior Rating Scale (VABS-C), which were used at baseline, post-training, and 3-month follow-up.
UNASSIGNED: There were significant differences for intellectual function and adaptive functioning between the two groups. The CCT group showed significant improvements in total full-scale intelligence quotient (FSIQ) score the Wechsler Intelligence Scale (F[60] = 31.97, p < 0.01) and its subdomain VIQ score (F[60] = 33.83, p < 0.01). For adaptive functioning, CCT had a better adaptive developmental quotient (ADQ) score (F[60] = 28.05, p < 0.01), and subdomain communication (F[60] = 10.86, p < 0.01) and socialization scores (F[60] = 4.35, p < 0.015). Moreover, there was a positive correlation between FSIQ changes and ADQ changes in the CCT group (rs = 0.74, p < 0.01). A greater increase in VIQ score was associated with a greater increase in adaptive functioning (bootstrapping CI: [0.16, 3.30]) in the CCT group.
UNASSIGNED: Multi-domain CCT improves the intellectual function and adaptive functioning of children with IDD.

Two community-based cohorts of children with autism spectrum disorder, examined using similar assessment protocols, were pooled (n = 301) and subdivided according to history of regression. Those with regression (n = 62), 20.5% of the combined cohort, were contrasted with those without regression (n = 241) at first assessment (age range 19-60 months) and at 2-year follow-up on a range of measures. The regression group was significantly more functionally impaired, with regard to intellectual function (p < .001), language development (p < .001), and to severity of autism (p < .01) at both T1 and T2. Only 14 (23.3%) had a clearly identified underlying etiology [24 (18.6%) in the non-regressive group]. There were no significant differences between those who had regressed \'from normal\' and those who had regressed \'from low\' functioning.