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Background: Ketogenic diet is an effective therapy for patients with medically refractory epilepsy. It is generally well tolerated, with the most common side effects being gastrointestinal. Hepatic toxicity has been described as an uncommon side effect of ketogenic diet, usually with long-term use. However, there are limited data to implicate ketogenic diet in acute liver toxicity. Methods and results: We analyzed all patients who underwent elective inpatient ketogenic diet initiation at our institution from June 2019 to June 2022. Of the 25 patients reviewed, we found 6 patients who showed acute, asymptomatic changes in liver function tests during initiation, in both hepatocellular and cholestatic patterns. Two patients stopped the ketogenic diet acutely and 3 patients continued ketogenic diet with changes in medications and/or addition of choline—all patients had improvement and normalization of liver function tests in the short term. One patient had acute normalization of chronically elevated liver function tests on ketogenic diet initiation. Conclusion: Ketogenic diet can cause acute changes in liver function tests during initiation of ketogenic diet, with both hepatocellular and cholestatic patterns, with and without the concurrent use of hepatotoxic medications. In most patients, ketogenic diet can be continued successfully by making changes to medications or addition of choline. [ABSTRACT FROM AUTHOR]

Genetic alterations leading to overactivation of mammalian target of rapamycin (mTOR) signaling result in brain overgrowth syndromes such as focal cortical dysplasia (FCD) and megalencephaly. Megalencephaly with cutis tri‐color of the Blaschko‐linear type pigmentary mosaicism and intellectual disability is a rare neurodevelopmental disorder attributed to the recurrent mosaic c.5930C > T (p.Thr1977Ile) MTOR variant. This variant was previously reported at low to intermediate levels of mosaicism in the peripheral blood of three unrelated individuals with consistent clinical findings. We report a fourth case of a 3‐year‐old female presenting with megalencephaly, obstructive hydrocephalus due to cerebral aqueductal stenosis, asymmetric polymicrogyria, dysgenesis of the corpus callosum, hypotonia, developmental delay, and cutaneous pigmentary mosaicism. Oligonucleotide and SNP chromosomal microarray (CMA), karyotype, and trio whole exome sequencing (WES) in the peripheral blood, as well as a targeted gene variant panel from fibroblasts derived from hyperpigmented and non‐hyperpigmented skin did not detect any abnormalities in MTOR or other genes associated with brain overgrowth syndromes. Unlike the previously reported cases, the de novo c.5930C > T (p.Thr1977Ile) MTOR variant was detected at 32% mosaicism in our patient only after WES was performed on fibroblast‐derived DNA from the hyperpigmented skin. This case demonstrates the tissue variability in mosaic expression of the recurrent p.Thr1977Ile MTOR variant, emphasizes the need for skin biopsies in the genetic evaluation of patients with skin pigmentary mosaicism, and expands the clinical phenotype associated with this pathogenic MTOR variant. [ABSTRACT FROM AUTHOR]