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Heterozygous loss of function variants in the IRF2BPL are a newly described cause of neurodevelopmental disabilities and epilepsy. As of 2019, fewer than 20 patients have been described in the published literature. This article reports an additional case of a patient with a pathogenic IRF2BPL variant and offers a comprehensive review of the published cases of individuals with IRF2BPL variants, in order to help expand the phenotype. The patient has a history of infantile spasms evolving into drug-resistant epilepsy with underlying epileptic encephalopathy consistent with Lennox-Gastaut syndrome. While at the extreme end of the spectrum, his phenotype is consistent with those previously described. Our literature review highlights the wide range of phenotypes exhibited by those with diseases related to IRF2BPL gene variants. This article also briefly discusses other comorbidities seen in the patient and those previously reported. While the molecular underpinnings of the role of IRF2BPL gene in the central nervous system are newly established, the specifics of its effects elsewhere have yet to be delineated. Furthermore, its pathogenesis in other organ systems is not yet understood and could be of importance from a management perspective.

Diagnosing complex V deficiencies caused by new variants in mitochondrial DNA is challenging due to the rarity, phenotypic diversity, and limited functional assessments. We describe a child with the m.9032T > C variant in MT-ATP6 encoding p.(Leu169Pro), with primary presentation of microcephaly, ataxia, hearing loss, and lactic acidosis. Functional studies reveal abnormal fragment F1 of complex V on blue native gel electrophoresis. Respirometry showed excessively tight coupling through complex V depressing oxygen consumption upon ADP stimulation and an excessive increase following uncoupling, in the presence of upregulation of mitochondrial biogenesis. These data add evidence about pathogenicity and functional impact of this variant.

Objectives:To report 2 additional cases of pyruvate dehydrogenase complex deficiency with reversible deep gray matter lesions following initiation of ketogenic diet and to perform a literature review of serial imaging in patients with pyruvate dehydrogenase complex.Methods:Clinical data on 3 previously unpublished cases of patients with pyruvate dehydrogenase complex deficiency and with serial magnetic resonance imagings (MRIs) before and after institution of ketogenic diet were reported. A systematic literature review was performed to search for published cases of patients with confirmed pyruvate dehydrogenase complex deficiency who underwent serial MRIs.Results:The 3 subjects in this series demonstrated clinical improvement on ketogenic diet. Two subjects showed reversal of some brain lesions on repeat MRI following initiation of ketogenic diet. Of the 21 published cases with serial MRIs, 13 patients underwent some form of treatment, and of this smaller subset 4 patients had repeat MRIs that showed definitive improvement. In both our described cases and those published in the literature, improvement occurred in lesions in the basal ganglia.Conclusions:In patients with pyruvate dehydrogenase complex deficiency, basal ganglia lesions on MRI are reversible with treatment in some cases and could serve as a biomarker for measuring response to treatment.