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11 795 záznamů v Medvik Filtry

Článek

Clinical severity and cardiac phenotype in phosphomannomutase 2-congenital disorders of glycosylation : Insights into genetics and management recommendations

Holubova, Veronika
Autor Holubova, Veronika Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
Barone, Rita
Autor Barone, Rita Child Neuropsychiatry-Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy Oasi Research Institute-IRCCS, Troina, Italy
Grunewald, Stephanie
Autor Grunewald, Stephanie Metabolic Unit, Great Ormond Street Hospital and Institute of Child Health, University College London, NHS Trust, London, UK
Tesařová, Markéta
Autor Tesařová, Markéta Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
Hansíková, Hana
Autor Hansíková, Hana Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
Augustínová, Jana
Autor Augustínová, Jana Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
Sykut-Cegielska, Jolanta
Autor Sykut-Cegielska, Jolanta Department of Inborn Errors of Metabolism and Paediatrics, Institute of Mother and Child, Warsaw, Poland
De Nictolis, Francesca
Autor De Nictolis, Francesca Division of Metabolism, Bambino Gesù Children's Research Hospital, Rome, Italy
Diaz-Moreno, Unai
Autor Diaz-Moreno, Unai Neurology Department, Hospital Sant Joan de Déu, U-703 Centre for Biomedical Research on Rare Diseases (CIBER-ER), Instituto de Salud Carlos III, Barcelona, Spain
Elangovan, Ramyia
Autor Elangovan, Ramyia Metabolic Unit, Great Ormond Street Hospital and Institute of Child Health, University College London, NHS Trust, London, UK

Journal of inherited metabolic disease. 2025 ; 48 (1) : e12826. [pub] 20241205

J Inherit Metab Dis
ISSN 1573-2665
Medvik
Zdroj

Cardiac involvement (CI) in phosphomannomutase 2-congenital disorders of glycosylation (PMM2-CDG) is part of the multisystemic presentation contributing to high mortality rates. The most common cardiac manifestations are pericardial effusion, cardiomyopathy, and structural heart defects. A genotype-phenotype correlation with organ involvement has not yet been described. We analyzed clinical, biochemical, and molecular genetic data of 222 patients from eight European centers and characterized the natural course of patients with CI. Fifty-seven patients (45 children) presented with CI, of whom 24 died (median age 21 months, standard deviation 49.8). Pericardial effusion was the most frequent manifestation (55.4%), occurring mostly within the first 6 months of life. The most common pathogenic variants in patients with CI were p.(Arg141His) in 74%, followed by p.(Val231Met) in 36%, which is 3.5 times higher than in PMM2-CDG patients without CI (p < 0.0001). Twenty-one out of 36 patients with p.(Val231Met) had CI; among them, 15 died, compared to 33 out of 166 patients without p.(Val231Met) who had CI (p < 0.0001). Nine out of 33 patients died (p = 0.0015), indicating greater clinical severity. Furthermore, the p.(Val231Met) variant is predominant in Eastern Europe, suggesting a founder effect. Cardiac complications in PMM2-CDG patients are common and serious. The variant p.(Val231Met) profoundly influences the extent of CI and mortality rates. Therefore, we recommend cardiac surveillance be included in the follow-up protocols for PMM2-CDG.

MeSH
dítě MeSH
fenotyp * MeSH
fosfotransferasy (fosfomutasy) * genetika nedostatek MeSH
genetické asociační studie MeSH
kardiomyopatie genetika MeSH
kojenec MeSH
lidé MeSH
mladiství MeSH
mutace MeSH
novorozenec MeSH
předškolní dítě MeSH
stupeň závažnosti nemoci MeSH
vrozené poruchy glykosylace * genetika MeSH
Check Tag
dítě MeSH
kojenec MeSH
lidé MeSH
mladiství MeSH
mužské pohlaví MeSH
novorozenec MeSH
předškolní dítě MeSH
ženské pohlaví MeSH
Publikační typ
časopisecké články MeSH
multicentrická studie MeSH
práce podpořená grantem MeSH
Geografické názvy
Evropa MeSH

Článek

Assessment of urinary 6-oxo-pipecolic acid as a biomarker for ALDH7A1 deficiency

Journal of inherited metabolic disease. 2025 ; 48 (1) : e12783. [pub] 20240722

J Inherit Metab Dis
ISSN 1573-2665
Medvik
Zdroj

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
aldehyddehydrogenasa nedostatek genetika MeSH
biologické markery * moč MeSH
dítě MeSH
epilepsie moč MeSH
kojenec MeSH
kyselina 2-aminoadipová moč analogy a deriváty MeSH
kyseliny pipekolové * moč MeSH
lidé MeSH
lysin nedostatek moč MeSH
mitochondriální aldehyddehydrogenasa nedostatek genetika MeSH
novorozenec MeSH
předškolní dítě MeSH
pyridoxin nedostatek moč terapeutické užití MeSH
Check Tag
dítě MeSH
kojenec MeSH
lidé MeSH
mužské pohlaví MeSH
novorozenec MeSH
předškolní dítě MeSH
ženské pohlaví MeSH
Publikační typ
časopisecké články MeSH
práce podpořená grantem MeSH
Research Support, N.I.H., Extramural MeSH

Článek

Tofacitinib in Pregnancy: Assessing Pregnancy and Infant Outcomes, Cord Blood, and Breast Milk Concentrations

Clinical gastroenterology and hepatology. 2025 ; 23 (1) : 163-165.e3. [pub] 20240201

Clin Gastroenterol Hepatol
ISSN 1542-7714
Medvik
Zdroj

Janus kinase (JAK) inhibitors are effective anti-inflammatory agents for treatment of ulcerative colitis (UC).1 According to drug regulatory agencies and international guidelines, JAK inhibitors should be avoided during pregnancy and lactation.2-4 The existing evidence on safety of JAK inhibitors during pregnancy is scarce and almost exclusively limited to tofacitinib.4-7.

MeSH
dospělí MeSH
fetální krev * chemie MeSH
inhibitory Janus kinas terapeutické užití MeSH
komplikace těhotenství farmakoterapie MeSH
lidé MeSH
mateřské mléko * chemie MeSH
novorozenec MeSH
piperidiny * terapeutické užití MeSH
pyrimidiny * terapeutické užití MeSH
těhotenství MeSH
ulcerózní kolitida farmakoterapie krev MeSH
výsledek těhotenství * MeSH
Check Tag
dospělí MeSH
lidé MeSH
novorozenec MeSH
těhotenství MeSH
ženské pohlaví MeSH
Publikační typ
časopisecké články MeSH

Článek

Diagnosis, treatment, management and monitoring of patients with tyrosinaemia type 1: Consensus group recommendations from the German-speaking countries

Journal of inherited metabolic disease. 2025 ; 48 (1) : e12824. [pub] -

J Inherit Metab Dis
ISSN 1573-2665
Medvik
Zdroj

Hepatorenal tyrosinaemia (HT1) is an autosomal recessive disorder of tyrosine degradation resulting in hepatic and renal dysfunction, neurological sequelae may occur in some patients. The use of nitisinone (NTBC) has revolutionised treatment and outcome of this disorder. NTBC has to be combined with a low protein diet. While NTBC modulates the disease course in HT1 patients, several issues are open. Optimal dosage, doses per day, therapeutic range of NTBC concentration, mode of protein restriction and biomarkers are not well defined. HCC and neurocognitive deficits are long-term sequelae. Early diagnosis and treatment are essential to minimise the risk for these complications. Clinical guidance for management of HT1-patients is required. Randomised clinical studies are difficult in the presence of therapeutic options. We discussed these issues in a consensus group of 10 paediatricians, 1 adult hepatologist, 1 geneticist, 2 dieticians, 2 newborn screening specialists with experience in HT1, 1 psychologist and 2 representatives of a patient group from the German-speaking countries (DACH). Recommendations were based on scientific literature and expert opinion, also taking into account recent experience with newborn screening. There was strong consensus that newborn screening using succinylacetone (SA) and early treatment are essential for a good outcome. The dose of NTBC should be as low as possible without losing metabolic control. This has to be accompanied by a low protein diet, in some patients a simplified diet without calculation of protein intake. Specific education and psychosocial support are recommended. Indications for liver transplantation were defined. Monitoring shall include clinical findings, levels of SA, tyrosine, phenylalanine and NTBC in (dried) blood.