Urea cycle disorders in Spain: an observational, cross-sectional and multicentric study of 104 cases

Martín‐Hernández, Elena; Aldámiz‐Echevarría, Luis; Castejón-Ponce, E.; Pedrón‐Giner, Consuelo; Couce, María L.; Serrano-Nieto, Juliana; Pintos-Morell, Guillem; Bélanger-Quintana, Amaya; Martínez‐Pardo, Mercedes; García‐Silva, María Teresa; Quijada‐Fraile, Pilar; Vitoria, Isidro; Dalmau, Jaime; Lama-More, R A; Bueno-Delgado, María Amor; Toro-Riera, Mirella del; García-Jiménez, Inmaculada; Sierra-Córcoles, Concepción; Ruiz-Pons, Mónica; Quintana, Luis Peña; Vives-Piñera, Inmaculada; Morais, Ana Heloneida de Araújo; Balmaseda-Serrano, E M; Meavilla, Silvia; Sanjurjo-Crespo, Pablo; Pérez‐Cerdá, Celia

doi:10.1186/s13023-014-0187-4

Cited by 37 publications

(57 citation statements)

References 43 publications

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“…To shorten the time to diagnosis, an electronic medical record‐based warning system to consider ammonia measurement has been suggested for neonates aged 2 to 7 days, on whom blood gas analyses are undertaken . Respiratory alkalosis in a newborn is present in up to 50% of acute UCDs and should prompt immediate ammonia measurement . There are clinically relevant pre‐analytical pitfalls with respect to collection, handling, storage, and analysis of blood samples for ammonia analysis …”

Section: Suggested Guidelinesmentioning

confidence: 99%

“…The risk of hyperammonemia in ASLD is low with arginine treatment, as two waste nitrogen atoms are excreted with each ASA molecule. However, a significant proportion of ASLD patients has a poor cognitive outcome even without hyperammonemic decompensation . This raises concerns regarding brain toxicity of ASA, of increased guanidinoacetate concentrations, nitric oxide (NO) production, or a role of altered arginine metabolism.…”

Section: Recommendations For Specific Disordersmentioning

confidence: 99%

See 1 more Smart Citation

Suggested guidelines for the diagnosis and management of urea cycle disorders: First revision

Häberle

Burlina²,

Chakrapani

et al. 2019

J of Inher Metab Disea

323

478

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In 2012, we published guidelines summarizing and evaluating late 2011 evidence for diagnosis and therapy of urea cycle disorders (UCDs). With 1:35 000 estimated incidence, UCDs cause hyperammonemia of neonatal (~50%) or late onset that can lead to intellectual disability or death, even while effective therapies do exist. In the 7 years increased awareness among health professionals and patient families. However, underrecognition and delayed diagnosis of UCDs still appear widespread. It was therefore necessary to revise the original guidelines to ensure an up-to-date frame of reference for professionals and patients as well as for awareness campaigns. This was accomplished by keeping the original spirit of providing a trans-European consensus based on robust evidence (scored with GRADE methodology), involving professionals on UCDs from nine countries in preparing this consensus. We believe this revised guideline, which has been reviewed by several societies that are involved in the management of UCDs, will have a positive impact on the outcomes of patients by establishing common standards, and spreading and harmonizing good practices. It may also promote the identification of knowledge voids to be filled by future research.

show abstract

Section: Suggested Guidelinesmentioning

confidence: 99%

Section: Recommendations For Specific Disordersmentioning

confidence: 99%

Suggested guidelines for the diagnosis and management of urea cycle disorders: First revision

Häberle

Burlina²,

Chakrapani

et al. 2019

J of Inher Metab Disea

323

478

View full text Add to dashboard Cite

show abstract

“…Liver complications have been observed in both early-onset and late-onset forms of ASLD and in patients treated with standard therapies (4). These complications in ASLD may be demonstrated by elevated transaminases, abnormal liver echogenicity on ultrasound, hepatomegaly, hepatic fibrosis, cirrhosis with portal hypertension, and impaired synthetic function, which -in some patients -has necessitated liver transplantation (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). Common liver histopathologic findings in patients with ASLD and other UCDs include hepatocyte enlargement with pallor, increased glycogen deposition, steatosis, fibrosis, and nodularity (10-12, 15, 20-22).…”

Section: Introductionmentioning

confidence: 99%

Chronic liver disease and impaired hepatic glycogen metabolism in argininosuccinate lyase deficiency

Burrage¹,

Madan²,

Li³

et al. 2020

JCI Insight

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BACKGROUND. Liver disease in urea cycle disorders (UCDs) ranges from hepatomegaly and chronic hepatocellular injury to cirrhosis and end-stage liver disease. However, the prevalence and underlying mechanisms are unclear. METHODS. We estimated the prevalence of chronic hepatocellular injury in UCDs using data from a multicenter, longitudinal, natural history study. We also used ultrasound with shear wave elastography and FibroTest to evaluate liver stiffness and markers of fibrosis in individuals with argininosuccinate lyase deficiency (ASLD), a disorder with high prevalence of elevated serum alanine aminotransferase (ALT). To understand the human observations, we evaluated the hepatic phenotype of the Asl Neo/Neo mouse model of ASLD. RESULTS. We demonstrate a high prevalence of elevated ALT in ASLD (37%). Hyperammonemia and use of nitrogen-scavenging agents, 2 markers of disease severity, were significantly (P < 0.001 and P = 0.001, respectively) associated with elevated ALT in ASLD. In addition, ultrasound with shear wave elastography and FibroTest revealed increased echogenicity and liver stiffness, even in individuals with ASLD and normal aminotransferases. The Asl Neo/Neo mice mimic the human disorder with hepatomegaly, elevated aminotransferases, and excessive hepatic glycogen noted before death (3-5 weeks of age). This excessive hepatic glycogen is associated with impaired hepatic glycogenolysis and decreased glycogen phosphorylase and is rescued with helper-dependent adenovirus expressing Asl using a liverspecific (ApoE) promoter. CONCLUSION. Our results link urea cycle dysfunction and impaired hepatic glucose metabolism and identify a mouse model of liver disease in the setting of urea cycle dysfunction. TRIAL REGISTRATION. This study has been registered at ClinicalTrials.gov (NCT03721367, NCT00237315).

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“…Interestingly, ASSD was only observed as neonatal presentation. This is an important result since knowing about the fact that ASSD was the predominantly reported UCD presented during neonatal period by Spanish national study (11) .…”

Section: Neonatal-onset Ucdmentioning

confidence: 68%

Presentation and management of classical urea cycle disorders: lessons from our experience

Uçar¹,

Canda²,

Köse³

et al. 2016

BUCH

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Objective:The urea cycle disorders (UCD) are inherited deficiencies of the enzymes or transport molecules involved in the cellular excretion of excess ammonia produced during protein metabolism. The aim of this study was to evaluate the clinical characteristics and long-term outcome of pediatric patients with UCD seen during childhood. Methods: Clinical characteristics in 13 patients with classical UCD (carbamoyl phosphate synthetase I deficiency (n=4), argininosuccinate lyase deficiency (n=4), argininosuccinate synthetase deficiency (n=3), arginase deficiency (n=1), and ornithine transcarbamylase deficiency (n=1)) were defined. The term "neonatal-onset" UCD was used if symptoms occurred within 28 days of life, and "late-onset" if symptoms started after that period. Results: The majority of patients (n=9) presented with acute metabolic crisis during newborn period. Core clinical phenotype in neonatal-onset UCD included sepsis-like neonatal crisis revealed in patients within 28 days after birth, whereas mental retardation was predominant peculiarity in late-onset UCD emerging more than 28 days after birth. Vomiting and hypotonia were frequently reported in neonatalonset UCD, and epilepsy with/without movement disorder was found in late-onset UCD patients. For patients with neonatal-onset UCD hyperammonemia was more severe at first diagnosis of the disease, and remained near upper limits of normal during the follow-up period. However, hyperammonemia and metabolic crisis have been reported lomber spinal stenoz frequently in symptomatic patients. A cardinal principal of UCD in acute and long-term management of UCD. Despite these evolving treatment opportunities, still higher mortality rates were found in neonatal-onset UCD (44% (4/9)). Conclusion: Neonatal-onset UCD were generally presents itself as acute onset hyperammonemia during the newborn period. However, neurological manifestations were reportedly more diagnostic in the lateonset UCD. It has been concluded that the basic principles of diagnosis and treatment need to be reorganized to improve recognition and outcome in these diseases. ÖZAmaç: Doğuştan metabolik hastalıklardan olan üre döngüsü hastalıkları (ÜDH), proteinlerin yıkımı sonucu oluşan amonyağın hücresel atılımında görevli enzim ve taşıyıcı moleküllerinin eksikliği sonucu oluşmaktadır. Bu çalışmanın amacı, çocukluk çağında görülen ÜDH klinik özelliklerini ve uzun dönem izlem sonuçlarını değerlendirmektir. Yöntemler: Klasik ÜDH (Karbamoil fosfat sentetaz I eksikliği (n=4), Arjininosüksinat liyaz eksikliği (n=4), Arjninosüksinat sentetaz eksikliği (n=3), Arjinaz eksikliği eksikliği (n=1), Ornitin transkarbamilaz eksikliği (n=1)) olan 13 hastanın klinik özellikleri belirlenmiştir. Semptomların 28 günden küçük hastalarda ortaya çıkması durumunda yenidoğan-başlangıçlı ÜDH, 28 günden sonra ortaya çıkan ÜDH için geç-başlangıçlı sözü kullanılmıştır. Bulgular: Hastaların büyük bir çoğunluğu (n=9) yenidoğan döneminde akut metabolik kriz ile ortaya çıkmıştır. Yenidoğan-başlangıçlı ÜDH sepsis benzeri bir tablo il...

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Urea cycle disorders in Spain: an observational, cross-sectional and multicentric study of 104 cases

Cited by 37 publications

References 43 publications

Suggested guidelines for the diagnosis and management of urea cycle disorders: First revision

Suggested guidelines for the diagnosis and management of urea cycle disorders: First revision

Chronic liver disease and impaired hepatic glycogen metabolism in argininosuccinate lyase deficiency

Presentation and management of classical urea cycle disorders: lessons from our experience

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