Mitochondrial disorder due to a defect in mitochondrial protein synthesis
-Rare developmental defect during embryogenesis
-Rare genetic disease
-Rare neurologic disease
Comment:
TUFM (= COXPD4, EFTU) is a mitochondrial protein that potently associates with NLR X1, and ATg12–ATg5 and ATg16L1. TUFM is known to be important in mitochondrial protein elongation. Overexpression and RNA interference targeting TUFM showed that the protein substantially inhibits RLR activation/type I IFN production, but augments autophagy (PMID:23321557). A mutation in the mitochondrial elongation factor Tu (EFTu) is described in Valente et al. (2007). A G-A transition at np 1016 of the cDNA converts the R residue at position 339 into a Q residue (R339Q) (PMID:17160893).
Valente et al. (2007) described 2 infants with neonatal lactic acidosis, rapidly progressive encephalopathy, severely decreased mitochondrial protein synthesis, and combined deficiency of mtDNA-related mitochondrial respiratory chain (MRC) complexes. One had a mutation in the EFG1 gene (GFM1; ... Valente et al. (2007) described 2 infants with neonatal lactic acidosis, rapidly progressive encephalopathy, severely decreased mitochondrial protein synthesis, and combined deficiency of mtDNA-related mitochondrial respiratory chain (MRC) complexes. One had a mutation in the EFG1 gene (GFM1; 606639) and thus had COXPD1. The other had an extremely severe syndrome dominated by lactic acidosis and rapidly fatal encephalopathy, with diffuse cystic leukodystrophy and micropolygyria, a developmental abnormality of the brain that occurs well before birth. Two days after birth, the infant developed acute respiratory distress and severe metabolic acidosis, with 2 episodes of generalized hypertonus. Serum lactic acid was markedly elevated. Brain CT scan showed several hypodense lesions. The lactic acidosis was partially corrected by intraveneously administered bicarbonate. She was relatively well until the age 6 months, when she had another episode of severe metabolic crisis. Thereafter acute episodes punctuated a relentless downhill course characterized by severe psychomotor regression with microcephaly, generalized axial hypotonia with limb spasticity, and nystagmus. Modest elevation of hepatic enzymes in blood and episodic hyperammonemia indicated mild liver involvement that never progressed to hepatic failure. Other tissues, notably the heart, were clinically spared. The patient died at the age of 14 months.