Experience of a Single Center in NTBC Use in Management of Hereditary Tyrosinemia Type I in Libya

Abstract

Background:Hereditary Tyrosinemia type I (HTI) is a metabolic disease caused by deficiency of fumarylacetoacetate hydrolase enzyme.Objectives:This study reports beside its clinical and biochemical presentation, the outcome of NTBC [2- (2-nitro-4-trifloro-methylbenzoyl)-1, 3-cyclohexanedion] treatment of the disease and evaluates its biochemical markers in 16 pediatric Libyan patients.Patients and Methods:The diagnosis was based on presence of high tyrosine levels in blood and succinylacetone in urine.Results:The consanguinity rate was 81.2%, the median age at onset, at diagnosis and at starting treatment were 4.5, 8, and 9.5 months respectively. At presentation hepatomegaly, jaundice, rickets and high gamma glutamyl transferase (GGT) were observed in 87.5% of patients. All patients had extremely high alpha fetoprotein (AFP) and high alkaline phosphatase (ALP) levels. Fifteen patients were treated with NTBC, normalization of PT (Prothrombine time) was achieved in average in 14 days. The other biochemical parameters of liver function (transaminases, GGT, ALP, bilirubin and albumin) took longer to improve and several months to be normalized. Survival rate with NTBC was 86.6%. Patients who started treatment in a median of 3 months post onset observed a fast drop of AFP in 90.6% of patients (P = 0.003). Abnormal liver function and rickets were the common presentations, GGT was an early cholestatic sensitive test. ALP was constantly high even in asymptomatic patients.Conclusions:In HT1 a faster dropping of AFP is a marker of good prognosis.

Oxidative Stress, Glutathione Metabolism, and Liver Regeneration Pathways Are Activated in Hereditary Tyrosinemia Type 1 Mice upon Short-Term Nitisinone Discontinuation

“…Ggt1 encodes an enzyme that catalyzes the transfer of the glutamyl moiety of glutathione (GSH) to a variety of amino acids and dipeptide acceptors. The observed highly increased gene expression of Ggt1 in Fah-deficient liver tissue after short-term NTBC deprivation is in accordance with high gamma glutamyl transferase activity levels observed in untreated HT1 patients [ 36 ]. Slc7a11 encodes the cystine/glutamate antiporter (xCT) and imports cystine as a precursor for GSH synthesis that supports antioxidant responses [ 37 ].…”

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

“…Other reported adverse effects of NTBC are relatively uncommon, minor, and/or transient and usually do not require disruption of NTBC treatment. The most frequently reported adverse effects (except for ocular problems) are leukopenia, thrombocytopenia, or granulocytopenia (all < 10%), and pruritus, exfoliative dermatitis, erythematous rash, myoclonia, or constipation (all < 1%) [12, 14, 45, 46, 50, 63, 95].…”

Revisiting hereditary tyrosinemia Type 1—spectrum of radiological findings

“…According to age at start of symptoms it is classified as acute (<6 months), subacute (6–12 months), and chronic (>1 year) forms. 3 α feto protein level was strikingly raised in our patient and was clinically thought to have hepatoblastoma or hepatocellular carcinoma; however, imaging refuted this suspicion. It is known that alfa feto protein is a sensitive but not a specific marker for hepatocellular carcinoma.…”

“…4 The most helpful test is to test succinylacetone levels in urine, plasma or dried blood spot. 3 Screening the newborns can lead to early diagnosis of the disease. 5…”