Search

The MT‐TL2 m.12315G>A pathogenic variant has previously been reported in five individuals with mild clinical phenotypes. Herein we report the case of a 5‐year‐old child with heteroplasmy for this variant who developed neurological regression and stroke‐like episodes similar to those observed in mitochondrial encephalopathy, lactic acidosis, and stroke‐like episodes (MELAS). Biochemical evaluation revealed depletion of arginine on plasma amino acid analysis and low z‐scores for citrulline on untargeted plasma metabolomics analysis. These findings suggested that decreased availability of nitric oxide may have contributed to the stroke‐like episodes. The use of intravenous arginine during stroke‐like episodes and daily enteral L‐citrulline supplementation normalized her biochemical values of arginine and citrulline. Untargeted plasma metabolomics showed the absence of nicotinamide and 1‐methylnicotinamide, and plasma total glutathione levels were low; thus, nicotinamide riboside and N‐acetylcysteine therapies were initiated. This report expands the phenotype associated with the rare mitochondrial variant MT‐TL2 m.12315G>A to include neurological regression and a MELAS‐like phenotype. Individuals with this variant should undergo in‐depth biochemical analysis to include untargeted plasma metabolomics, plasma amino acids, and glutathione levels to help guide a targeted approach to treatment. [ABSTRACT FROM AUTHOR]

Trisomy 16 is the most common autosomal trisomy in humans, which is almost uniformly embryonic lethal. Partial trisomy 16 including a segment of the long arm of chromosome 16 is occasionally compatible with life and has been associated with severe congenital defects, growth retardation, and early lethality. Segmental trisomy of 16q is usually described concomitantly with partial monosomy of another chromosome, often resulting from a parental balanced translocation. Pure partial chromosome 16q trisomy is exceedingly rare. About nine children with 16q12→qter and 16q13→qter duplication have been reported in the literature, almost all described with monosomy of a second chromosome, and highlighting very few long‐term survivors. A single individual with pure partial distal 16q12.1q23.3 duplication has been reported in an infant, underscoring complexities of genetic counseling and management, especially in view of life‐limiting congenital anomalies in rare survivors. Here, we present a 12‐month‐old child with pure 16q12.2q24.3 trisomy, having continued morbidity related to pulmonary hypertension and chronic lung disease. The features of intrauterine growth retardation, facial dysmorphism, hypotonia, congenital heart defect, distal contractures, urogenital abnormalities, and hearing loss support the association with 16q partial trisomy, as in previous studies. This report expands our current understanding related to the survival of infants with large segmental aneusomy of the long arm of chromosome 16. [ABSTRACT FROM AUTHOR]