Skip to main content

Table 2 Comparison of biochemical and gene testing for diagnosis of PKU

From: A comprehensive multiplex PCR based exome-sequencing assay for rapid bloodspot confirmation of inborn errors of metabolism

Newborn

Fluorometric assay

Phenylalanine levels (mg/dl)

PEARS-101 test

Original bloodspot

Repeat bloodspot

PKU Diagnosis

PAH variants detected

Predicted amino acid change

Pathogenicity Classification*

Diagnosis

Retrospective study (n = 9)

 PKU-1

9.71

10.5

Moderate

c.827 T > A

p.M276K

Pathogenic

PKU

c.728G > A

p.R243Q

Pathogenic

 PKU-2

15.4

40.4

Severe

c.1197A > T

p.V399 V#

Pathogenic

PKU

c.728G > A

p.R243Q

Pathogenic

 PKU-3

19.1

21.7

Severe

c.1215_1219del

p.T405 fs

Pathogenic

PKU

c.1199 + 1G > C

mRNA splicing

Pathogenic

 PKU-4

26.9

36.2

Severe

c.1197A > T

p.V399 V#

Pathogenic

PKU

c.740G > T

p.G247 V

Pathogenic

 PKU-5

14.6

45.8

Severe

c.1197A > T

p.V399 V#

Pathogenic

Normal

 PKU-6

12.5

39.2

Severe

c.331C > T

p.R111X

Pathogenic

PKU

c.611A > G

p.Y204C

Pathogenic

 PKU-7

22.8

30.0

Severe

c.1197A > T

p.V399 V#

Pathogenic

PKU

c.728G > A

p.R243Q

Pathogenic

 PKU-8

19.3

30.9

Severe

c.331 C > T

p.R111X

Pathogenic

PKU

c.782G > A

p.R261Q

Pathogenic

 PKU-9

6.3

9.7

Moderate

c.721C > T

p.R241C

Pathogenic

PKU

c.728G > A

p.R243Q

Pathogenic

Prospective study (n = 211)

 S-43

10.4

36.9

Severe

c.611A > G

p.Y204C

Pathogenic

PKU

c.47-48del

p.S16 fs

Pathogenic

 S-109

5.4

8.1

Moderate

c.782G > A

p.R261Q

Pathogenic

PKU

c.721C > T

p.R241C

Pathogenic

 S-119

<  2.0

ND

Normal

c.1064C > A

p.Y356X

Pathogenic

Normal

 S1-S208*

<  2.0

ND

Normal

None

Not relevant

Not relevant

Normal

  1. *By definition of a clinical diagnosis of PKU, all newly detected PKU variants can be classified as pathogenic; # Silent mutation; ND Not Done; *S1-S208 (excluding S-43, S-109 and S-119)