Thiamine transporter-2 deficiency is a recessive disease caused by mutations in the SLC19A3 gene. Patients manifest acute episodes of encephalopathy; symmetric lesions in the cortex, basal ganglia, thalami or periaqueductal gray matter, and a dramatic response to biotin or thiamine. We report a 30-day-old patient with mutations in the SLC19A3 gene who presented with acute encephalopathy and increased level of lactate in the blood (8.6 mmol/L) and cerebrospinal fluid (7.12 mmol/L), a high excretion of α-ketoglutarate in the urine, and increased concentrations of the branched-chain amino acids leucine and isoleucine in the plasma. MRI detected bilateral and symmetric cortico-subcortical lesions involving the perirolandic area, bilateral putamina, and medial thalami. Some lesions showed low apparent diffusion coefficient values suggesting an acute evolution; others had high values likely to be subacute or chronic, most likely related to the perinatal period. After treatment with thiamine and biotin, irritability and opisthotonus disappeared, and the patient recovered consciousness. Biochemical disturbances also disappeared within 48 hours. After discontinuing biotin, the patient remained stable for 6 months on thiamine supplementation (20 mg/kg/day). The examination revealed subtle signs of neurologic sequelae, and MRI showed necrotic changes and volume loss in some affected areas. Our observations suggest that patients with thiamine transporter 2 deficiency may be vulnerable to metabolic decompensation during the perinatal period, when energy demands are high. Thiamine defects should be excluded in newborns and infants with lactic acidosis because prognosis largely depends on the time from diagnosis to thiamine supplementation.
BackgroundThe clinical characteristics distinguishing treatable thiamine transporter-2 deficiency (ThTR2) due to SLC19A3 genetic defects from the other devastating causes of Leigh syndrome are sparse.MethodsWe report the clinical follow-up after thiamine and biotin supplementation in four children with ThTR2 deficiency presenting with Leigh and biotin-thiamine-responsive basal ganglia disease phenotypes. We established whole-blood thiamine reference values in 106 non-neurological affected children and monitored thiamine levels in SLC19A3 patients after the initiation of treatment. We compared our results with those of 69 patients with ThTR2 deficiency after a review of the literature.ResultsAt diagnosis, the patients were aged 1 month to 17 years, and all of them showed signs of acute encephalopathy, generalized dystonia, and brain lesions affecting the dorsal striatum and medial thalami. One patient died of septicemia, while the remaining patients evidenced clinical and radiological improvements shortly after the initiation of thiamine. Upon follow-up, the patients received a combination of thiamine (10–40 mg/kg/day) and biotin (1–2 mg/kg/day) and remained stable with residual dystonia and speech difficulties. After establishing reference values for the different age groups, whole-blood thiamine quantification was a useful method for treatment monitoring.ConclusionsThTR2 deficiency is a reversible cause of acute dystonia and Leigh encephalopathy in the pediatric years. Brain lesions affecting the dorsal striatum and medial thalami may be useful in the differential diagnosis of other causes of Leigh syndrome. Further studies are needed to validate the therapeutic doses of thiamine and how to monitor them in these patients.
Despite the rarity of thiamine transporter-2 deficiency, it should be suspected in patients with acute dystonia and basal ganglia injury, as thiamine can halt disease evolution and prevent further episodes. © 2012 Movement Disorder Society.
BackgroundDespite therapeutic hypothermia 30-70% of newborns with moderate or severe hypoxic ischemic encephalopathy will die or survive with significant long-term impairments. Magnetic resonance imaging (MRI) in the first days of life is being used for early identification of these infants and end of life decisions are relying more and more on it. The purpose of this study was to evaluate how MRI performed around day 4 of life correlates with the ones obtained in the second week of life in infants with hypoxic-ischemic encephalopathy (HIE) treated with hypothermia.MethodsProspective observational cohort study between April 2009 and July 2011. Consecutive newborns with HIE evaluated for therapeutic hypothermia were included. Two sequential MR studies were performed: an •early’ study around the 4th day of life and a •late’ study during the second week of life. MRI were assessed and scored by two neuroradiologists who were blinded to the clinical condition of the infants.ResultsForty-eight MRI scans were obtained in the 40 newborns. Fifteen infants underwent two sequential MR scans. The localization, extension and severity of hypoxic-ischemic injury in early and late scans were highly correlated. Hypoxic-ischemic injury scores from conventional sequences (T1/T2) in the early MRI correlated with the scores of the late MRI (Spearman ρ = 0.940; p < .001) as did the scores between diffusion-weighted images in early scans and conventional images in late MR studies (Spearman ρ = 0.866; p < .001). There were no significant differences in MR images between the two sequential scans.ConclusionsMRI in the first days of life may be a useful prognostic tool for clinicians and can help parents and neonatologist in medical decisions, as it highly depicts hypoxic-ischemic brain injury seen in scans performed around the second week of life.
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