Treatment of two children with hereditary tyrosinaemia type I and long‐standing renal disease with a 4‐hydroxyphenylpyruvate dioxygenase inhibitor (NTBC)

Renal tubular function in children with tyrosinaemia type I treated with nitisinone

“…The effect of nitisinone on serial markers of renal tubular dysfunction has been described previously in small cohorts (Lindstedt et al 1992;Pronicka et al 1996). To our knowledge, the effect of nitisinone on renal tubular dysfunction in TTI has not been described in a large series of patients.…”

Early effect of NTBC on renal tubular dysfunction in hereditary tyrosinemia type 1

“…So far, a few studies reported on the long-term outcome of renal tubular dysfunction in HT1 patients receiving NTBC therapy [13][14][15][16]. In 1992, within the original cohort of HT1 patients where the efficacy of NTBC was first demonstrated, Lindstedt et al described one patient with renal involvement who normalized tubular dysfunction markers on a Table 2 Markers of tubular function in patient #5, before and after 14 days after the start of NTBC.…”

“…Phosphatemia, which was maintained close to normal by 300 mg/day phosphate supplementation, normalized as well in 1 month even when supplementation was stopped [13]. Some years later, a study focused on the NTBC effects on long-standing renal involvement in two HT1 patients was reported [14]. They presented with a sub-acute/ chronic form showing rickets as a dominant clinical feature with hypophosphatemia, hypocalcemia, high alkaline phosphatase levels, reduced TRP along with aminoaciduria, high fractional urate excretion, bicarbonate loss and elevated α 1 -microglobulin in urine.…”

“…The early effect of NTBC on liver disease has been studied and demonstrated its efficacy in improving liver function within the first day(s) after its start [10][11][12]. On the other hand, the effect of NTBC on renal tubule has so far been poorly investigated, with only a few studies showing its effects over the first months of therapy [13][14][15][16]. In this report we describe in detail the early effect of NTBC on renal tubular disease in patients with HT1 over the first two weeks of treatment.…”

Kidneys of Mice With Hereditary Tyrosinemia Type I Are Extremely Sensitive to Cytotoxicity

“…NTBC reduces the accumulation of FAA by blocking the activity of 4-hydroxyphenylpyruvate dioxygenase (HPD), an enzyme acting upstream of FAH ( Fig. 1), and has been shown to improve both liver and kidney function in approximately 90% of HT1 patients (12)(13)(14). The 10% of patients not responding to NTBC remain dependent on OLT for survival (15).…”