Absence of a significant renal threshold for two aromatic acids in phenylketonuric children over two years of age

Abstract

There is a steady and nonlinear relationship between the levels of both phenylpyruvic acid (PPA) and o-hydroxyphenylacetic acid (oOPAA) in urine and the plasma levels of phenylalanine (phe) in children more than two years of age with phenylketonuria (PKU). If phe levels in blood rise above 0.35 mM (5.8 mg/100 ml) both aromatic acids are found regularly in urine. Typically, urinary concentrations of PPA are about 5 times higher than those of oOPAA. This report is based on the analysis of 94 samples from 51 children, on or off diet.

A synopsis of the unconjugated acidic transamination metabolites of phenylalanine in phenylketonuria

“…The data are compiled in Table 1 and Figure 1 and reveal a distinct pattern of metabolic relations, of which the absence of a significant renal threshold has already been described before for oOPAA and PPA (Langenbeck et al, 1980b). Also, PLA is seen in most of the urine samples at plasma phe concentrations below 0.4 mmol/L.…”

“…Gas chromatographic analysis of 0.5-ml urine samples preserved with sodium dithionite (Na2S204) has been described in detail before (Langenbeck et al, 1978a(Langenbeck et al, , 1980b. Briefly, on a packed t80-cm OV-1 column with flame ionization detection, PPA was determined as benzylquinoxalinol-TMSi-ether, the other acids as trimethylsilyl ether esters, all with 2-oxo-n-valeric acid (OVA) as internal standard.…”

“…Briefly, on a packed t80-cm OV-1 column with flame ionization detection, PPA was determined as benzylquinoxalinol-TMSi-ether, the other acids as trimethylsilyl ether esters, all with 2-oxo-n-valeric acid (OVA) as internal standard. The molar response factors (MRF) were 1.121 _+ 6.9% (n = 6), 0.708 _+_ 11.4% (n= 6), and 0.769 4-7.4% (n = 11) for PLA, oOPAA, and PPA, respectively (Langenbeck et at., 1980b). The molar o-phenylenediamine excess at 10mmol/L PPA was still 18-fold.…”

Renal transport of aromatic acids in patients with phenylketonuria

“…Highest PPA levels are around 1 mol/mol creatinine. They occur at plasma phenylalanine concentrations of about 1.1 mmol/1 and higher (see Figure 1 and Langenbeck et aL, 1980a).…”

Study on urinary metabolic profile of phenylketonuria by micellar electrokinetic capillary chromatography with dual electrochemical detection—Potential clinical application in fast diagnosis of phenylketonuria

“…Since it is relatively difficult and unsafe to collect the newborn children's blood, as well as to convince the parents to accept such practice, an alternative noninvasive method has been developed for early diagnosis of PKU based on the measurement of abnormal aromatic acids resulted from phenylalanine metabolic disorder in urine samples. Some researches have shown that above two diagnosis methods are equally reliable [6,7], and such approaches as ferric chloride and dinitrophenylhydrazine methods [8], photometry [9], flow injection with chemiluminescence detection [10], HPLC [11][12][13], GC-MS [14][15][16] and CE-UV [17][18][19] have been employed for the analysis of urinary aromatic acids including phenylpyruvic acid (PPA). However, most of abovementioned instruments are relatively complicated and expensive, and/or need time-consuming derivatization procedures prior to analysis.…”