Cystathionine β-Synthase Deficiency in the E-HOD Registry-Part II: Dietary and Pharmacological Treatment

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11320%2F25%3A10490462" target="_blank" >RIV/00216208:11320/25:10490462 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/25:10490462 RIV/00064165:_____/25:10490462

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=gMnOw6jTdk" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=gMnOw6jTdk</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/jimd.12844" target="_blank" >10.1002/jimd.12844</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Cystathionine β-Synthase Deficiency in the E-HOD Registry-Part II: Dietary and Pharmacological Treatment

Popis výsledku v původním jazyce

Cystathionine beta-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 mu mol/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 mu mol/L, but many NRs and PRs had a mean tHcy considerably above 100 mu mol/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).

Název v anglickém jazyce

Cystathionine β-Synthase Deficiency in the E-HOD Registry-Part II: Dietary and Pharmacological Treatment

Popis výsledku anglicky

Cystathionine beta-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 mu mol/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 mu mol/L, but many NRs and PRs had a mean tHcy considerably above 100 mu mol/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).

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30202 - Endocrinology and metabolism (including diabetes, hormones)

Projekt

<a href="/cs/project/NU23-07-00383" target="_blank" >NU23-07-00383: Vzácné poruchy metabolismu sirných aminokyselin: nové diagnostické postupy a detailní fenotypové projevy (RADISUM)</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Inherited Metabolic Disease

ISSN

0141-8955

e-ISSN

1573-2665

Svazek periodika

48

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

15

Strana od-do

e12844

Kód UT WoS článku

001395462500001

EID výsledku v databázi Scopus

2-s2.0-85215503478