ALDH7A1 deficiency is an epileptic encephalopathy whose seizures respond to treatment with supraphysiological doses of pyridoxine. It arises as a result of damaging variants in ALDH7A1, a gene in the lysine catabolism pathway. α-Aminoadipic semialdehyde (α-AASA) and Δ1-piperideine-6-carboxylate (P6C), which accumulate because of the block in the lysine pathway, are diagnostic biomarkers for this disorder. Recently, it has been reported that 6-oxo-pipecolic acid (6-oxo-PIP) also accumulates in the urine, CSF and plasma of ALDH7A1-deficient individuals and that, given its improved stability, it may be a more suitable biomarker for this disorder. This study measured 6-oxo-PIP in urine from a cohort of 30 patients where α-AASA was elevated and showed that it was above the normal range in all those above 6 months of age. However, 6-oxo-PIP levels were within the normal range in 33% of the patients below 6 months of age. Levels increased with age and correlated with a decrease in α-AASA levels. Longitudinal analysis of urine samples from ALDH7A1-deficient patients who were on a lysine restricted diet whilst receiving supraphysiological doses of pyridoxine showed that levels of 6-oxo-PIP remained elevated whilst α-AASA decreased. Similar to α-AASA, we found that elevated urinary excretion of 6-oxo-PIP can also occur in individuals with molybdenum cofactor deficiency. This study demonstrates that urinary 6-oxo-PIP may not be a suitable biomarker for ALDH7A1 deficiency in neonates. However, further studies are needed to understand the biochemistry leading to its accumulation and its potential long-term side effects.
- MeSH
- Aldehyde Dehydrogenase deficiency genetics MeSH
- Biomarkers * urine MeSH
- Child MeSH
- Epilepsy urine MeSH
- Infant MeSH
- 2-Aminoadipic Acid urine analogs & derivatives MeSH
- Pipecolic Acids * urine MeSH
- Humans MeSH
- Lysine deficiency urine MeSH
- Aldehyde Dehydrogenase, Mitochondrial deficiency genetics MeSH
- Infant, Newborn MeSH
- Child, Preschool MeSH
- Pyridoxine deficiency urine therapeutic use MeSH
- Check Tag
- Child MeSH
- Infant MeSH
- Humans MeSH
- Male MeSH
- Infant, Newborn MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
Cystathionine β-synthase (CBS) deficiency (classical homocystinuria) has a wide range of severity. Mildly affected patients typically present as adults with thromboembolism and respond to treatment with pyridoxine. Severely affected patients usually present during childhood with learning difficulties, ectopia lentis and skeletal abnormalities; they are pyridoxine non-responders (NR) or partial responders (PR) and require treatment with a low-methionine diet and/or betaine. The European network and registry for Homocystinurias and methylation Defects (E-HOD) has published management guidelines for CBS deficiency and recommended keeping plasma total homocysteine (tHcy) concentrations below 100 μmol/L. We have now analysed data from 311 patients in the registry to see how closely treatment follows the guidelines. Pyridoxine-responsive patients generally achieved tHcy concentrations below 50 μmol/L, but many NRs and PRs had a mean tHcy considerably above 100 μmol/L. Most NRs were managed with betaine and a special diet. This usually involved severe protein restriction and a methionine-free amino acid mixture, but some patients had a natural protein intake substantially above the WHO safe minimum. Work is needed on the methionine content of dietary protein as estimates vary widely. Contrary to the guidelines, most NRs were on pyridoxine, sometimes at dangerously high doses. tHcy concentrations were similar in groups prescribed high or low betaine doses and natural protein intakes. High tHcy levels were probably often due to poor compliance. Comparing time-to-event graphs for NR patients detected by newborn screening and those ascertained clinically showed that treatment could prevent thromboembolism (risk ratio 0.073) and lens dislocation (risk ratio 0.069).
- MeSH
- Betaine * therapeutic use MeSH
- Cystathionine beta-Synthase deficiency MeSH
- Child MeSH
- Adult MeSH
- Homocysteine * blood metabolism MeSH
- Homocystinuria * drug therapy MeSH
- Infant MeSH
- Humans MeSH
- Methionine * deficiency MeSH
- Adolescent MeSH
- Young Adult MeSH
- Infant, Newborn MeSH
- Child, Preschool MeSH
- Pyridoxine * therapeutic use MeSH
- Registries * MeSH
- Treatment Outcome MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Infant MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Infant, Newborn MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- MeSH
- Graves Disease * diagnosis drug therapy MeSH
- Weight Loss MeSH
- Hyperthyroidism diagnosis drug therapy MeSH
- Middle Aged MeSH
- Humans MeSH
- Methimazole administration & dosage therapeutic use MeSH
- Delayed Diagnosis MeSH
- Pyridoxine administration & dosage therapeutic use MeSH
- Antithyroid Agents MeSH
- Vitamin B Complex MeSH
- Vitamin D administration & dosage therapeutic use MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Publication type
- Case Reports MeSH
- MeSH
- Dopamine Antagonists administration & dosage therapeutic use MeSH
- Anti-Allergic Agents administration & dosage therapeutic use MeSH
- Hyperemesis Gravidarum diet therapy drug therapy complications physiopathology MeSH
- Pregnancy Complications * MeSH
- Humans MeSH
- Nausea diet therapy drug therapy prevention & control MeSH
- Pyridoxine administration & dosage therapeutic use MeSH
- Pregnancy MeSH
- Zingiber officinale MeSH
- Vomiting diet therapy drug therapy prevention & control MeSH
- Check Tag
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
Cystathionine β-synthase (CBS) deficiency has a wide clinical spectrum, ranging from neurodevelopmental problems, lens dislocation and marfanoid features in early childhood to adult onset disease with predominantly thromboembolic complications. We have analysed clinical and laboratory data at the time of diagnosis in 328 patients with CBS deficiency from the E-HOD (European network and registry for Homocystinurias and methylation Defects) registry. We developed comprehensive criteria to classify patients into four groups of pyridoxine responsivity: non-responders (NR), partial, full and extreme responders (PR, FR and ER, respectively). All groups showed overlapping concentrations of plasma total homocysteine while pyridoxine responsiveness inversely correlated with plasma/serum methionine concentrations. The FR and ER groups had a later age of onset and diagnosis and a longer diagnostic delay than NR and PR patients. Lens dislocation was common in all groups except ER but the age of dislocation increased with increasing responsiveness. Developmental delay was commonest in the NR group while no ER patient had cognitive impairment. Thromboembolism was the commonest presenting feature in ER patients, whereas it was least likely at presentation in the NR group. This probably is due to the differences in ages at presentation: all groups had a similar number of thromboembolic events per 1000 patient-years. Clinical severity of CBS deficiency depends on the degree of pyridoxine responsiveness. Therefore, a standardised pyridoxine-responsiveness test in newly diagnosed patients and a critical review of previous assessments is indispensable to ensure adequate therapy and to prevent or reduce long-term complications.
- MeSH
- Cystathionine beta-Synthase deficiency MeSH
- Child MeSH
- Adult MeSH
- Phenotype MeSH
- Homocystinuria diagnosis drug therapy enzymology MeSH
- Infant MeSH
- Middle Aged MeSH
- Humans MeSH
- Linear Models MeSH
- Methionine blood MeSH
- Adolescent MeSH
- Young Adult MeSH
- Delayed Diagnosis MeSH
- Child, Preschool MeSH
- Pyridoxine therapeutic use MeSH
- Registries MeSH
- Aged MeSH
- Severity of Illness Index MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Infant MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Child, Preschool MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Europe MeSH
LCIG je účinnou liečbou pokročilého štádia Parkinsonovej choroby. Jednou z obávaných komplikácii tejto liečby je polyneuropatia, ktorá môže zásadne ovplyvniť motorické aj non-motorické funkcie pacienta a kvalitu jeho života. Vo väčšine prípadov ide o metabolicky podmienenú polyneuropatiu v dôsledku užívania levodopy, a tým spojenej elevácie homocysteínu a deficitu vitamínov skupiny B. V prípade výskytu akútnej polyneuropatie je potrebné vylúčiť Guillainov-Barrého syndróm a ukončiť liečbu LCIG. U každého pacienta by sa malo myslieť na uvedenú komplikáciu, a to už pred zvažovanou indikáciou a následne aj počas celej doby liečby LCIG.
LCIG is an effective treatment for the advanced stage of Parkinson's disease. Serious complication of this treatment is polyneuropathy, which can signifficantly influenced motor and non-motor functions of the patient and the quality of life. In most of the cases there is a metabolic cause of polyneuropathy due to the usage of levodopa, associated with elevation of homocysteine and deficiency of vitamins B. In case of acute polyneuropathy, it is necessary to exclude Guillain-Barré Syndrome and discontinue LCIG treatment. Each patient should be examined for polyneuropathy before the initiation of LCIG therapy and also during the treatment.
- MeSH
- Diagnosis, Differential MeSH
- Drug Combinations MeSH
- Gels therapeutic use MeSH
- Guillain-Barre Syndrome diagnosis MeSH
- Homocysteine metabolism MeSH
- Carbidopa therapeutic use MeSH
- Levodopa therapeutic use MeSH
- Humans MeSH
- Parkinson Disease drug therapy complications MeSH
- Polyneuropathies * chemically induced diagnosis drug therapy classification prevention & control MeSH
- Pyridoxine administration & dosage MeSH
- Vitamin B 12 administration & dosage MeSH
- Vitamins metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Práca sa zameriava na vývoj jednoduchej analytickej metódy na báze kapilárnej zónovej elektroforézy v spojení s UV-detekciou pre simultánne stanovenie tiamínu a pyridoxínu vo vzorkách farmaceutického a potravinárskeho charakteru. Separácia tiamínu a pyridoxínu prebiehala v elektrolytovom systéme 25 mmol ∙ l–1 GABA + 50 mmol ∙ l–1 HAc+ 0,05% m-HEC. Detekcia bola uskutočnená pri vlnovej dĺžke 260 nm. Medza detekcie pre tiamín bola 0,059 µg ∙ ml–1 a pre pyridoxín 0,23 µg ∙ ml–1. Tieto hodnoty naznačujú, že metóda je vhodná na stanovenie relatívne nízkych koncentrácií tiamínu a pyridoxínu. Uvedená CZE-UV metóda umožnila efektívne stanovenie obsahu dvojice vitamínov v piatich výživových doplnkoch a jedenástich energetických nápojoch a vitamínových vodách.
The paper is focused on development of a simple analytical method based on capillary zone electrophoresis in combination with UV-detection for simultaneous detemination of thiamine and pyridoxine in pharmaceutical and food samples. The separation of thiamine and pyridoxine was performed in a background electrolyte composed of 25 mmol ∙ l–1 GABA + 50 mmol ∙ l–1 HAc+ 0.05% m-HEC. The UV detector was set at the constant wavelength of 260 nm. Limit of detection was 0.059 µg ∙ ml–1 for thiamine and 0.23 µg ∙ ml–1 for pyridoxine. These levels suggest that relatively low quantities of thiamine and pyridoxine can be detected. The presented CZE-UV method enabled effective determination of the two vitamins in 5 food supplements and 11 energy drinks and vitamin waters.
The aim of the study was to contribute to scarce literature data on the content of selected vitamins and iodine in mare's milk. The study focused on the content of selected lipophilic vitamins (A, E), hydrophilic vitamins (B 1, B 2 , B 6 ) and iodine in milk samples obtained from 8 mares during 6 months of lactation. The content of micronutrients was evaluated according to the stage of lactation. Vitamins B 2 and B 6 were determined using ion-pair reversed phase high performance liquid chromatography with fluorescence detection, vitamin B1 by fluorescence detection by reversed-phase liquid chromatography, vitamins A and E by the ultra-high performance liquid chromatography method with ultraviolet and fluorescence detection and iodine by the spectrophotometric method. Mean concentrations of vitamins A (0.06 ± 0.08 mg/l), E (0.083 ± 0.14 mg/l), B 1 (256.24 ± 44.19 μg/l), B 2 (111.40 ± 81.88 μg/l), B 6 (0.30 ± 0.12 mg/l) reached lower values in mare's milk compared to cow's milk. The mean value of iodine in mare's milk reached 44.48 ± 54.45 μg/l. Lactation stage proved to be a significant factor for vitamin B6 and iodine.
- Keywords
- Tirovin,
- MeSH
- Fucus MeSH
- Hypothyroidism diet therapy MeSH
- Iodine therapeutic use MeSH
- Humans MeSH
- Copper therapeutic use MeSH
- Dietary Supplements MeSH
- Pyridoxine therapeutic use MeSH
- Thyrotropin MeSH
- Thyroxine MeSH
- Triiodothyronine MeSH
- Tyrosine therapeutic use MeSH
- Zinc therapeutic use MeSH
- Check Tag
- Humans MeSH
