Pregnancy in an NTBC‐Treated Patient With Hereditary Tyrosinemia Type I

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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“…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

172

222

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“…With the tremendously improved clinical outcome and survival probability, pregnancy in TT1-affected mothers treated with NTBC have been reported [162–164]. Not much is known about a possible teratogenic effect of NTBC.…”

Section: Future Considerations and Remaining Challenges For Tt1mentioning

confidence: 99%

“…All three infants were healthy without signs of malformations and had normal development later on while receiving between 0.5 and 1.0 mg/kg NTBC during pregnancy with maternal tyrosine concentrations up to 700–800 µmol/L [162–164]. After delivery, neonatal blood NTBC concentrations reduced slowly while receiving bottle feeding [163, 164], until SA became detectable in urine and AFP concentrations rose slightly after an initial decline 2 weeks after birth in the TT1-affected child [162]. All reported TT1 mothers were healthy with no sign of liver, renal or neurological deterioration during pregnancy [162–164].…”

Section: Future Considerations and Remaining Challenges For Tt1mentioning

confidence: 99%

Long-Term Outcomes and Practical Considerations in the Pharmacological Management of Tyrosinemia Type 1

et al. 2019

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Tyrosinemia type 1 (TT1) is a rare metabolic disease caused by a defect in tyrosine catabolism. TT1 is clinically characterized by acute liver failure, development of hepatocellular carcinoma, renal and neurological problems, and consequently an extremely poor outcome. This review showed that the introduction of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) in 1992 has revolutionized the outcome of TT1 patients, especially when started pre-clinically. If started early, NTBC can prevent liver failure, renal problems, and neurological attacks and decrease the risk for hepatocellular carcinoma. NTBC has been shown to be safe and well tolerated, although the long-term effectiveness of treatment with NTBC needs to be awaited. The high tyrosine concentrations caused by treatment with NTBC could result in ophthalmological and skin problems and requires lifelong dietary restriction of tyrosine and its precursor phenylalanine, which could be strenuous to adhere to. In addition, neurocognitive problems have been reported since the introduction of NTBC, with hypothesized but as yet unproven pathophysiological mechanisms. Further research should be done to investigate the possible relationship between important clinical outcomes and blood concentrations of biochemical parameters such as phenylalanine, tyrosine, succinylacetone, and NTBC, and to develop clear guidelines for treatment and follow-up with reliable measurements. This all in order to ultimately improve the combined NTBC and dietary treatment and limit possible complications such as hepatocellular carcinoma development, neurocognitive problems, and impaired quality of life. Key Points Treatment with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) has been found to be generally safe and has clearly improved treatment and outcomes for patients with tyrosinemia type 1.

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“…There were no reported adverse effects on fetal development in the three children of women with tyrosinemia type I treated with NTBC during pregnancy. Development and general health of all three infants during the first year were reported as normal [183][184][185]. However, developing fetus may be at risk because of alterations in tyrosine metabolism and thus follow-up should be performed for infants born to women treated with NTBC during pregnancy.…”

Section: Tyrosinemia Type I and Pregnancymentioning

confidence: 98%

Disorders of phenylalanine and tyrosine metabolism

Alsharhan

Fıçıcıoğlu

2020

TRD

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This article provides a review of the inborn errors of phenylalanine and tyrosine metabolism including the diagnostic approach, dietary and pharmalogical management and emerging therapies. Hyperphenylalaninaemia results mainly from defects in either phenylalanine hydroxylase (PAH) (resulting in phenylketonuria (PKU)) or the production or recycling of tetrahydrobiopterin (BH 4). Untreated PKU results in irreversible neurocognitive impairment. Five inherited disorders of tyrosine metabolism are known, which include tyrosinemia type I, type II, type III, hawkinsinuria and alkaptonuria. Newborn screening for these disorders has enabled their early detection and decreased the associated morbidity and mortality.

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Pregnancy in an NTBC‐Treated Patient With Hereditary Tyrosinemia Type I

Cited by 14 publications

References 12 publications

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

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

Long-Term Outcomes and Practical Considerations in the Pharmacological Management of Tyrosinemia Type 1

Disorders of phenylalanine and tyrosine metabolism

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