The once-daily reduced dosing frequency is approved for use in patients who weigh 20 kg or more and who have undetectable serum and urine succinylacetone
concentrations after a minimum of 4 weeks on a stable twice-daily dosage of nitisinone.
In follow up, regular abdominal USG was performed every 6-12 months and AFP levels, plasma amino acids and urine succinylacetone
were checked every 3 months.
His serum and urine tyrosine level were elevated at 942 nmol/mL and 26082.7 nmol/mL, respectively; however, succinylacetone
was not detected in the urine.
150 [micro]l of the internal standard for succinylacetone
was added to the remaining blood spots.
NeoMass AAAC is used with Tandem Mass Spectrometry to detect concentrations of amino acids, free carnitine, acylcarnitines, succinylacetone
and argininosuccinic acid.
This reduced dosing frequency is approved for use in patients five years of age and older who have undetectable serum and urine succinylacetone
concentrations after a minimum of four weeks on a stable dosage of nitisinone.
In fact, nitisinone 2-(2-nitro-4-trifluoro-methylbenzyol)-1,3 cyclohexanedione, NTBC) is a potent inhibitor of 4-hydroxyphenylpyruvate dioxygenase, an enzyme that is upstream of fumarylacetoacetase, and most patients present a rapid decrease in the concentrations of succinylacetone
(2) when under NTBC.
Cause Assessment method Syphilis Quantitative nontreponemal serologic test Toxoplasmosis Serology (IgG and IgM) Rubella Serology (IgG and IgM) Cytomegalovirus Serology (IgG and IgM) and urinary PCR Herpes simplex virus Serology (IgG and IgM) Parvovirus B19 PCR Infection/sepsis Blood culture, urine culture, and chest X-ray Hepatitis viruses A, B, and C Serology (IgG and IgM) Tyrosinemia Urinary succinylacetone
Galactosemia Galactose-1-phosphate uridyltransferase Hereditary fructose intolerance Transferrin isoelectric focusing Niemann-Pick type C disease Filipin test Gaucher disease Leukocyte glucocerebrosidase activity Alpha-1-antitrypsin deficiency Detection of PiZ allele PCR = polymerase chain reaction.
The accumulation of the toxic metabolites succinylacetone
and fumarylacetoacetate in the liver and kidneys leads to death if not treated.
FAH deficiency leads to an accumulation of fumarylacetoacetate, maleylacetoacetate, succinylacetoacetone, and succinylacetone
. Maleylacetoacetate causes renal tubular dysfunction in a Fanconi-like syndrome of renal failure and vitamin D-resistant rickets (Jacobs, van Beurden, Klomp, Berger, & van den Berg, 2006).
Such amino acids as threonine and glycine can be converted to RCS (e.g., methylglyoxal (MGO)) or their precursors (e.g., aminoacetone and succinylacetone
) during oxidative modification .