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Myopathy, lactic acidosis, and sideroblastic anemia 2 (MLASA2) is an autosomal recessive mitochondrial disorder caused by pathogenic variants in YARS2. YARS2 variants confer heterogeneous phenotypes ranging from the full MLASA syndrome to a clinically unaffected state. Symptom onset is most common in the first decade of life but can occur in adulthood and has been reported following intercurrent illness. Early death can result from respiratory muscle weakness and cardiomyopathy. We report a case of MLASA2 with compound heterozygous YARS2 pathogenic variants; a known pathogenic nonsense variant [NM_001040436.3:c.98C>A (p.Ser33Ter)] and a likely pathogenic missense variant not previously associated with disease [NM_001040436.3:c.948G>T (p.Arg316Ser)]. The proband initially presented with a relatively mild phenotype of myopathy and lactic acidosis. During pregnancy, anemia emerged as an additional feature and in the postpartum period she experienced severe decompensation of cardiorespiratory function. This is the first reported case of pregnancy‐related complications in a patient with YARS2‐related mitochondrial disease. This case highlights the need for caution and careful counseling when considering pregnancy in mitochondrial disease, due to the risk of disease exacerbation and pregnancy complications. [ABSTRACT FROM AUTHOR]

Accentuated blood pressure (BP) fluctuation and low cerebral blood flow (CBF) response to CO2 increase the risk of transient ischemic attack (TIA) recurrence and stroke in TIA patients. Improving cardio- and cerebrovascular function may reduce stroke risk. We found dietary nitrate lowered dynamic blood pressure variability (BPV) in rats and improved cerebrovascular CO2 reactivity in healthy individuals. In 30 TIA patients, we examined the effects of a 7-day supplementation of dietary nitrate (0.1 mmol·kg-1·day-1) on cerebrovascular function using a randomized, single-blinded, placebo-controlled study design. We hypothesized that 7-day dietary nitrate supplementation would decrease variabilities in BP and CBF and improve CBF-CO2 slope and cerebral autoregulation (CA). We assessed beat-to-beat middle cerebral artery blood velocity (MCAv; index of CBF) and BP at rest and during CO2 breathing. Transfer function analysis was performed on beat-to-beat MCAv and BP to determine CA parameters (gain, phase, and coherence). Irrespective of treatment, high- and low-frequency BP-MCAv gain and MCAv-CO2 slope increased 7 days following TIA onset, while low-frequency BPV decreased (P < 0.05 vs. baseline). At follow-up, dietary nitrate elevated plasma nitrate concentration by ~547% (P < 0.001) and moderately lowered BPV (d = 0.6, P = 0.011), MCAv variability (d = 0.7, P = 0.018), and BP-MCAv coherence (d = 0.7, P = 0.008) in the very-low-frequency range (0.02-0.07 Hz), while MCAv-CO2 slope and arterial stiffness were unaffected (P > 0.05). Concurrent with standard treatment, dietary nitrate supplementation reduces BP and CBF fluctuation and improves cerebral autoregulation in TIA patients, without affecting cerebrovascular CO2 reactivity. NEW & NOTEWORTHY We found dietary nitrate supplementation reduced blood pressure and brain blood flow fluctuations and improved the relationship between blood pressure and brain blood flow in transient ischemic attack patients. Meanwhile, dietary nitrate had no effects on the brain blood vessels' response to CO2. We attribute the improved brain blood flow stability to the improved myogenic control of blood pressure with dietary nitrate. Our findings indicate that dietary nitrate could be an effective strategy for stabilizing blood pressure and brain blood flow following transient ischemic attack. [ABSTRACT FROM AUTHOR]