Clinical practice: NTBC therapy for tyrosinemia type 1: how much is enough?

• Published in: European journal of pediatrics 2010-06, Vol.169 (6), p.689-693
• Main Authors: El-Karaksy, Hanaa, Rashed, Mohmmad, El-Sayed, Rokaya, El-Raziky, Mona, El-Koofy, Nehal, El-Hawary, Manal, Al-Dirbashi, Osama
• Format: Article
• Language: English
• Subjects: Abdomen; Aminoacid disorders; Ascites; Biological and medical sciences; Child, Preschool; Clinical medicine; Cost-Benefit Analysis; Cyclohexanones - administration & dosage; Cyclohexanones - economics; Dietary restrictions; Dose-Response Relationship, Drug; Drug Costs; Egypt; Enzyme Inhibitors - administration & dosage; Enzyme Inhibitors - economics; Enzymes; Errors of metabolism; Female; General aspects; Heptanoates - blood; Humans; Infant; Liver; Medical sciences; Medicine; Medicine & Public Health; Metabolic diseases; Metabolism; Metabolites; Nitrobenzoates - administration & dosage; Nitrobenzoates - economics; Original Paper; Patients; Pediatrics; Phosphatase; Rickets; Thrombocytopenia; Tyrosinemias - drug therapy; Urine
• ISSN: 0340-6199; 1432-1076
• DOI: 10.1007/s00431-009-1090-1

Four patients with tyrosinemia type 1 (ages 6–32 months) were treated with 2-(2-nitro-4-trifluoro-methylbenzoyl)-1,3-cyclohexandion (NTBC) at Cairo University Children’s Hospital, Egypt and followed up for 12–27 months. The recommended average dose of NTBC is 1 mg/kg/day. They were started on the following doses: 0.8, 0.58, 0.5, and 0.625 mg/kg/day, respectively. Two months after start of therapy, succinylacetone was undetectable in patients 1, 2, and 4, while in case 3, it was 5.4 μM. Her NTBC dose was increased from 0.5 to 0.65 mg/kg/day, and succinylacetone was undetectable 1 month later. They were kept on NTBC doses ranging from 0.55 to 0.65 mg/kg/day. These doses allowed catch up growth, normalization of synthetic liver functions, steep drop in serum alpha fetoprotein, reduction in phosphate loss in urine, normalization of serum calcium, phosphate, and alkaline phosphatase, and healing of active rickets. Succinylacetone was undetectable in urine on these doses. In conclusion: Doses of NTBC, lower than recommended, may be helpful in treatment of tyrosinemia, on condition that succinylacetone production is suppressed, and AFP is maintained normal or showing a progressive decrease. This cost-effective dose may allow treatment of affected children from economically underprivileged countries, but longer follow up periods are needed.