Maternal and fetal tyrosinemia type I

Segarra, Nuria Garcia; Roche, Sophie; Imbard, Apolline; Benoist, Jean‐François; Greneche, Marie-Odile; Davit–Spraul, Anne; Baulny, Hélène Ogier de

doi:10.1007/s10545-012-9569-8

Cited by 20 publications

(14 citation statements)

References 10 publications

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“…[47] To that point, there have been two recent reports of administration of NTBC during gestation in patients with HT1. [48, 49] While this approach has potential therapeutic benefit, up to now there has been no suitable research model to test the effect of in utero administration of NTBC to the fetus in an appropriate preclinical model. The results presented here would strengthen the argument that a patient carrying a fetus known to be at high risk of liver damage caused by absence of a functional FAH gene should be given NTBC for the duration of pregnancy.…”

Section: Section 4: Discussionmentioning

confidence: 99%

Fumarylacetoacetate hydrolase deficient pigs are a novel large animal model of metabolic liver disease

et al. 2014

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Hereditary tyrosinemia type I (HT1) is caused by deficiency in fumarylacetoacetate hydrolase (FAH), an enzyme that catalyzes the last step of tyrosine metabolism. The most severe form of the disease presents acutely during infancy, and is characterized by severe liver involvement, most commonly resulting in death if untreated. Generation of FAH+/− pigs was previously accomplished by adeno-associated virus-mediated gene knockout in fibroblasts and somatic cell nuclear transfer. Subsequently, these animals were outbred and crossed to produce the first FAH−/− pigs. FAH-deficiency produced a lethal defect in utero that was corrected by administration of 2-(2-nitro-4-trifluoromethylbenzyol)-1,3 cyclohexanedione (NTBC) throughout pregnancy. Animals on NTBC were phenotypically normal at birth; however, animals were euthanized approximately four weeks after withdrawal of NTBC due to clinical decline and physical examination findings of severe liver injury and encephalopthy consistent with acute liver failure. Biochemical and histological analyses, characterized by diffuse and severe hepatocellular damage, confirmed the diagnosis of severe liver injury. FAH−/− pigs provide the first genetically engineered large animal model of a metabolic liver disorder. Future applications of FAH−/− pigs include discovery research as a large animal model of HT1 and spontaneous acute liver failure, and preclinical testing of efficacy of liver cell therapies, including transplantation of hepatocytes, liver stem cells, and pluripotent stem cell-derived hepatocytes.

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Section: Section 4: Discussionmentioning

confidence: 99%

Fumarylacetoacetate hydrolase deficient pigs are a novel large animal model of metabolic liver disease

et al. 2014

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“…Development and general health of all three infants during the first year were reported as normal. 103 , 105 , 106 …”

Section: Pregnancy and Ht-1mentioning

confidence: 99%

Diagnosis and treatment of tyrosinemia type I: a US and Canadian consensus group review and recommendations

Chinsky

Singh

Fıçıcıoğlu

et al. 2017

Genetics in Medicine

178

222

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Tyrosinemia type I (hepatorenal tyrosinemia, HT-1) is an autosomal recessive condition resulting in hepatic failure with comorbidities involving the renal and neurologic systems and long term risks for hepatocellular carcinoma. An effective medical treatment with 2-[2-nitro-4-trifluoromethylbenzoyl]-1,3-cyclohexanedione (NTBC) exists but requires early identification of affected children for optimal long-term results. Newborn screening (NBS) utilizing blood succinylacetone as the NBS marker is superior to observing tyrosine levels as a way of identifying neonates with HT-1. If identified early and treated appropriately, the majority of affected infants can remain asymptomatic. A clinical management scheme is needed for infants with HT-1 identified by NBS or clinical symptoms. To this end, a group of 11 clinical practitioners, including eight biochemical genetics physicians, two metabolic dietitian nutritionists, and a clinical psychologist, from the United States and Canada, with experience in providing care for patients with HT-1, initiated an evidence- and consensus-based process to establish uniform recommendations for identification and treatment of HT-1. Recommendations were developed from a literature review, practitioner management survey, and nominal group process involving two face-to-face meetings. There was strong consensus in favor of NBS for HT-1, using blood succinylacetone as a marker, followed by diagnostic confirmation and early treatment with NTBC and diet. Consensus recommendations for both immediate and long-term clinical follow-up of positive diagnoses via both newborn screening and clinical symptomatic presentation are provided.

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“…However, three patients on nitisinone have had babies who were normal on examination in the newborn period [41,42], unpublished case report. Early follow-up was also normal.…”

Section: Pregnancymentioning

confidence: 99%

“…This suggests that the tyrosine degradation pathway is active in utero . In one pregnancy both mother and baby had HT1, the nitisinone not only crossed the placenta freely but suppressed the disease in the fetus [42]. If NTBC is proved to be completely safe it might be given to the mother to prevent damage in utero.…”

Section: Pregnancymentioning

confidence: 99%

Recommendations for the management of tyrosinaemia type 1

Laet

Dionisi‐Vici

Leonard³

et al. 2013

Orphanet J Rare Dis

192

231

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The management of tyrosinaemia type 1 (HT1, fumarylacetoacetase deficiency) has been revolutionised by the introduction of nitisinone but dietary treatment remains essential and the management is not easy. In this review detailed recommendations for the management are made based on expert opinion, published case reports and investigational studies as the evidence base is limited and there are no prospective controlled studies.The added value of this paper is that it summarises in detail current clinical knowledge about HT1 and makes recommendations for the management.

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Maternal and fetal tyrosinemia type I

Cited by 20 publications

References 10 publications

Fumarylacetoacetate hydrolase deficient pigs are a novel large animal model of metabolic liver disease

Fumarylacetoacetate hydrolase deficient pigs are a novel large animal model of metabolic liver disease

Diagnosis and treatment of tyrosinemia type I: a US and Canadian consensus group review and recommendations

Recommendations for the management of tyrosinaemia type 1

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