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.

Hereditary tyrosinemia presenting as hepatocellular carcinoma in a young infant

“…There may be acute, subacute and chronic forms of presentation based on the age. 4 Acute presentation in children less than 6 months of age is the commonest, presenting with acute liver failure. 5 The earlier the presentation, the graver the outcome.…”

Hereditary Tyrosinemia Type 1—A Rare Disease with Typical Radiological Features: Case Report and Review of Literature

“…The presentation may be acute, subacute, or chronic based on age at presentation. 10 Acute presentation occurs in children <6 months of age, subacute in those presenting between 6 and 12 months of age, and chronic in patients presenting after 1 year of age. Majority of the patients present with acute form.…”

A Review of Metabolic Disorder of Amino Acid Tyrosinemia type I: When to Suspect and how to Diagnose

“…X-ray of wrist document possible presence of rickets resulting from renal tubular damage. Markedly elevated serum concentration of alpha-fetoprotein (average 160,000 ng/ml) (normal: <1000 ng/mL for infants age 1-3 months and <12 ng/mL for children age 3 months to 18 years) [22,25] but it is not specific, it is indicator of liver damage, however newborn babies diagnosed by screening have markedly raised AFP levels [26,27]. Elevated levels of SA in dried blood spots, plasma, or urine are pathognomonic, a routine organic acid assays may not be sufficiently sensitive to detect SA if it is very low or the urine very dilute, a specific assay is needed.…”

“…Nitisinone blocks the tyrosine catabolic pathway such that increases the blood concentration of tyrosine, blood tyrosine concentration greater than 600 mol/l confers risk of precipitation of tyrosine crystals in the cornea as bilateral, linear, branching subepithelial corneal opacities causing photophobia and itchy, sensitive eyes. [11,13].Failure to normalize of AFP or a secondary rise should be regarded with suspicion, imaging should be done without delay [25,27,39,42]. 5.4.…”