ABSTRACT
Vitamin B6 is a micronutrient required by the body. It acts as a coenzyme in biochemical reactions. Vitamin B6 toxicity is not caused by the intake of food-based sources. The few reported cases of vitamin B6 toxicity are always caused by overdosing of nutritional supplements. Chronic toxicity typically occurs with peripheral neuropathy such as paraesthesia, ataxia, and imbalance, paradoxically mimicking vitamin B6 deficiency. However, the prognosis is favorable, and symptoms usually show improvement once excessive vitamin B6 levels return to the physiological range. We report a newborn presenting with diffuse tremor at birth, interpreted as secondary to the mother's intake of high doses of a supplement containing vitamin B6 during pregnancy and breastfeeding. As expected, the newborn's serum levels of vitamin B6 were high. The tremors disappeared when the maternal supplement was stopped.
ABSTRACT
Enzyme replacement therapy is currently the only approved treatment for Pompe disease, due to acid α-glucosidase deficiency. Clinical efficacy of this approach is variable, and more effective therapies are needed. We showed in preclinical studies that chaperones stabilize the recombinant enzyme used for enzyme replacement therapy. Here, we evaluated the effects of a combination of enzyme therapy and a chaperone on α-glucosidase activity in Pompe disease patients. α-Glucosidase activity was analyzed by tandem-mass spectrometry in dried blood spots from patients treated with enzyme replacement therapy, either alone or in combination with the chaperone N-butyldeoxynojirimycin given at the time of the enzyme infusion. Thirteen patients with different presentations (3 infantile-onset, 10 late-onset) were enrolled. In 11 patients, the combination treatment resulted in α-glucosidase activities greater than 1.85-fold the activities with enzyme replacement therapy alone. In the whole patient population, α-glucosidase activity was significantly increased at 12 hours (2.19-fold, P = 0.002), 24 hours (6.07-fold, P = 0.001), and 36 hours (3.95-fold, P = 0.003). The areas under the curve were also significantly increased (6.78-fold, P = 0.002). These results suggest improved stability of recombinant α-glucosidase in blood in the presence of the chaperone.
Subject(s)
1-Deoxynojirimycin/analogs & derivatives , Glycogen Storage Disease Type II/blood , Glycogen Storage Disease Type II/drug therapy , Glycoside Hydrolase Inhibitors/pharmacology , alpha-Glucosidases/pharmacology , 1-Deoxynojirimycin/pharmacology , Adolescent , Adult , Animals , Child , Child, Preschool , Disease Models, Animal , Dried Blood Spot Testing , Drug Synergism , Enzyme Replacement Therapy/methods , Enzyme Stability , Female , Humans , Male , Mice , Middle Aged , Young Adult , alpha-Glucosidases/blood , alpha-Glucosidases/therapeutic useABSTRACT
BACKGROUND: Recurrent epistaxis is the most common manifestation of hereditary hemorrhagic telangiectasia (HHT). The aim of this study was to determine the role and efficacy of argon plasma coagulation (APC) in the management of epistaxis caused by HHT. METHODS: From 1997 to 2004, 43 patients with diagnosed HHT were treated for recurrent epistaxis with APC in our department. RESULTS: Thirty-six patients reported substantial reduction of bleeding after treatment. Of the 18 patients who previously needed blood transfusions, 13 reported substantial reduction of bleeding after treatment and no blood transfusions were necessary. CONCLUSION: APC allows a control of epistaxis in HHT patients and guarantees a long time free from blood transfusions. This treatment modality can be performed with local anesthesia, is not invasive, is well tolerated, is inexpensive, and can be used as a first step even in patients who need to undergo several blood transfusions for their epistaxis.