Amir Baikatov

Background/Objectives: Interpretation of amino-acid and acylcarnitine results in newborn screening depends on population-appropriate reference intervals (RIs), and no locally derived paediatric RIs have been published for the general Kazakhstan population. We aimed to establish the first age- and sex-specific RIs for a tandem mass spectrometry (MS/MS) panel measured from dried blood spots (DBSs) by flow injection analysis tandem mass spectrometry (FIA-MS/MS) in a Kazakhstani paediatric population using an indirect (data-mining) approach. Methods: All amino-acid and acylcarnitine results (1 January 2022 to the data freeze on 20 July 2026) were extracted from the consolidated laboratory information system of a 21-branch network; after cleaning, deduplication and selection of conditionally healthy subjects, RIs (2.5th, 50th, 97.5th percentiles with 90% bootstrap confidence intervals) were computed per CLSI EP28-A3c across CALIPER age strata, with the neonatal period split into 0–7/8–14/15–28-day strata, and cross-validated by the canonical refineR package run without flag-based selection, the CLIR/Mayo database and a comparable Turkish study. Results: From 687,726 results in 4198 patients, the conditionally healthy cohort comprised 3589 subjects; the large majority of analyte–age strata permitted full CLSI EP28 computation. Canonical refineR and flag-based estimates agreed within ±30% in 91% of key-marker limits (median relative difference 9.6%), indicating that flag-based selection did not materially bias the upper limits. Reference intervals are reported for all amino acids and all 36 acylcarnitines of the panel. The valine 97.5th-percentile upper limit exceeded its 250 µmol/L decision limit at 0–28 days (275.3 µmol/L). Conclusions: We provide locally derived and internally cross-checked paediatric MS/MS RIs, pending prospective verification, and flag two actionable findings: inter-site harmonisation of several key markers and the overlap of the upper-normal valine limit with its clinical decision limit.

To evaluate whether low-frequency transcranial magnetic stimulation (TMS) is associated with improvement in speech-language function in children with autism spectrum disorder (ASD) and Specific Language Impairment (SLI), a treatment response difference by stimulation frequency and cortical target was assessed. This retrospective observational study analyzed clinical data from 131 children treated at Neurolab Neurorehabilitation Center (Almaty, Kazakhstan), between April 3, 2023, and July 30, 2024. The cohort included 58 children with ASD and 73 children with SLI. Speech-language function was rated before and after treatment using a structured 10-point clinical scale. TMS was delivered to the bilateral dorsolateral prefrontal cortex (DLPFC), with additional stimulation of Broca's and/or Wernicke's areas in selected participants. Frequencies of 0.3 Hz, 0.5 Hz, and 1.0 Hz were analyzed. Each course consisted of 10 daily sessions. Across the total cohort, mean speech-language rating improved from 3.46 to 3.96 points, with a mean improvement of 0.50 points. Improvement was greater in children with ASD than in children with SLI (0.83 vs. 0.25 points). The strongest response was observed in the ASD subgroup treated at 1.0 Hz, where mean improvement reached 2.13 points. In an adjusted linear regression model, the ASD x 1.0 Hz interaction remained significant (coefficient=1.55, p=0.004), while number of treatment courses was positively associated with improvement and motor delays were negatively associated with improvement. Low-frequency TMS was associated with improvement in clinician-rated speech-language function, but the effect was not uniform across stimulation protocols. The findings support the potential of TMS as a protocol-sensitive neuromodulation approach and indicate the need for prospective studies comparing stimulation parameters directly. Key words: transcranial magnetic stimulation, autism spectrum disorder, specific language impairment, low-frequency stimulation, speech development, neuromodulation.