Abstract
A 17-month-old girl, with acute intermittent ataxia and drowsiness, had hypertyrosinemia (serum tyrosine, 62 μmole/dl) and phenolic aciduria in the absence of hepatic, renal, eye or skin lesions. Serum methionine and urinary >-aminotevulinic acid concentrations were normal. Her psychomotor development was also normal. Protein restriction and vitamin C therapy failed to correct the biochemical abnormality. Liver biopsy was histologically normal.
Analysis of the enzymes in the fiver biopsy, taken at 25 months of age, showed no detectable activity of 4-hydroxypbenylpyruvate dioxygenase (4HPPD), either in whole homogenate or cytosol fraction. Mixing experiments revealed no inhibitor of either 4HPPD or tyrosine aminotransferase (TAT).
TAT in unfractionated liver was 0.23 μmole/mg protein/h (control, 0.10–0.30 μmole/mg protein/h; n = 5). In mitochondria, TAT was 0.24 μmole/mg protein/h (control, 0.09–0.12 μmole/mg protein/h; n = 3) whereas in cytosol fraction it was 0.23 μmole/mg protein/h (control, 0.27–0.44 μmole/mg protein/h; n = 3). Glutamate dehydrogenase activity appeared in the cytosol fraction suggesting some rupture of mitochondria during fractionation of the patient's liver and indicating that true cytosol TAT might be somewhat lower than indicated; however, the kinetics of the patient's cytosol TAT were normal: Km for tyrosine, 4.5 X 10-3 M (control, 4.0 x 10-3 M); Km for α-ketoglutarate, 98 x 10-6 M (control, 75 X 10-6 M); approxhnate Km for pyridoxal phosphate, 2.1 X 10-6 M (control, 4.0 X 10-6 M). Vmax in patient liver was 0.37 μmole/mg protein/h (control, 0.88 μmole/mg protein/h). These data argue against a primary abnormality of TAT but are consistent with a defect of 4HPPD; thus, this patient appears to represent a previously undescribed form of tyrosinemia.
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Giardini, O., Cantani, A., Kennaway, N. et al. Chronic Tyrosinemia Associated with 4-Hydroxyphenylpyruvate Dioxygenase Deficiency with Acute Intermittent Ataxia and without Visceral and Bone Involvement. Pediatr Res 17, 25–29 (1983). https://doi.org/10.1203/00006450-198301000-00005
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DOI: https://doi.org/10.1203/00006450-198301000-00005
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