evaluation of plasma selenium level, glutathione peroxidase activity and thyroid functions in...
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Evaluation of Plasma Selenium Level, Glutathione Peroxidase Activity and
Thyroid Functions in Children with Phenylketonuria
Evaluation of Plasma Selenium Level, Glutathione Peroxidase Activity and
Thyroid Functions in Children with Phenylketonuria
*Rabah M. Shawky, *Eman A. Zaki, **Amr S. MoustafaPediatric* and Biochemistry** Departments,
Ain Shams Medical School, Cairo, Egypt
*Rabah M. Shawky, *Eman A. Zaki, **Amr S. MoustafaPediatric* and Biochemistry** Departments,
Ain Shams Medical School, Cairo, Egypt
PhenylketonuriaPhenylketonuria
Autosomal Recessive
Unless Treated, Irreversible MR
Newborn Screening
Autosomal Recessive
Unless Treated, Irreversible MR
Newborn Screening
Reactive Oxygen Species
Reactive Oxygen Species
• Singlet Oxygen (1O2)
• Superoxide (O2·)
• Hydroxyl (OH·)
• Peroxyl (ROO·) • Alkoxyl (RO·)
• Hydrogen Peroxide (H2O2)
Free Radical
Non Free Radical
Natural AntioxidantsNatural Antioxidants
Enzymes• Superoxide Dismutase• Catalase• Glutathione Peroxidase
Vitamins and Trace-elements • Water-Soluble: Vitamin C• Fat-Soluble: Vitamin A and E• Selenium
Oxidative StressOxidative Stress
The Imbalance between
ROS
Natural Antioxidants
The Imbalance between
ROS
Natural Antioxidants
Glutathione Peroxidase (GPX)
Glutathione Peroxidase (GPX)
• GPX Gene on Chromosome 3• GPX is a Selenoprotein
GSSG
GSHH2O2
H2OGPX
NADPH+H+
NADP+
PPP
Selenium (Se)Selenium (Se)
• Essential MicronutrientRDA and RNI
• Selenoproteins
• FunctionsAntioxidant Formation of Active T3Immune System Blood Clotting
GPX, Iodothyronine Deiodinase, …
Aim of the WorkAim of the Work
• Evaluation of the Changes in Plasma Se Level, GPX Activity and Thyroid Function Tests in PKU Patients
• This Would Allow Better Follow-up and Careful Adjusting of Dietary Management Protocols for PKU Patients
Work PlanWork Plan
Measurement of Plasma
• Se Level by Atomic Absorption
Measurement of Whole Blood • GPX Activity by Spectrophotometry
• T3, T4, and TSH Levels by Electrochemiluminesnce Immunoassay
• phe Level by HPLC
Age DistributionAge Distribution
0
1
2
3
4
5
6
7
8
9A
ge
( year
s
)
Cases Control
0%
10%
20%
30%
40%
50%
60%P
erce
nt
of
case
s
Cases Control
Males Females
Sex Distribution Sex Distribution
Consanguinity among PKU
Consanguinity among PKU
Consanguinity
Yes72%
No28%
Family History among PKU
Family History among PKUFamily History
Positive50%
Negative50%
GPX (U/L) of PKU Vs Controls
GPX (U/L) of PKU Vs Controls
0
500
1000
1500
2000
2500
3000
3500
4000
4500
5000
Wh
ole
Blo
od
GP
X
( U / L )
Cases Control
*
* Significant
Se (µg/dl) of PKU Vs Controls
Se (µg/dl) of PKU Vs Controls
0
2
4
6
8
10
12
14
16
18
20
Pla
sm
a S
e
( ug
/ dl
)
Cases Control
**
** Highly Significant
Mental Retardation among PKU
Mental Retardation among PKU
Below Average IQ
16 . 67 %
Severe MR 38 . 89 %
Moderate MR 33 . 33 %
Mild MR 11 . 11 %
Age at the time of Diagnosis of PKU
Age at the time of Diagnosis of PKU
Age at time of diagnosis
> 2 years
56 %
> 6 months to < 2 2years
33 %
< 6 months
11 %
years
The phe (mg/dl) Vs IQ among PKU
The phe (mg/dl) Vs IQ among PKUCases
0
5
10
15
20
25
30
0 20 40 60 80 100 120
IQ
Pla
sma
Phe
( mg
/ dl ) r = - 0.83; P <0.001 (Sig)
GPX (U/L) Vs IQ among PKU
GPX (U/L) Vs IQ among PKU
Cases
0
1000
2000
3000
4000
5000
6000
7000
8000
0 20 40 60 80 100 120
IQ
Wh
ole
Blo
od
GP
X
( U / L )
r = 0.62; P <0.01 (Sig)
ConclusionsConclusions
• Decreased Se level among PKU may be due to dietary restriction
• PKU is a state of oxidative stress that may be associated with the depletion of natural antioxidants
• Instead, Se deficiency may be a part of the pathology of PKU
• Follow-up of PKU with thyroid function tests is recommended with severe Se deficiency
• Dietary supplementation with Se is recommended for PKU to allow for The proper functions of selenoproteins
Conclusions (Cont’d)
Conclusions (Cont’d)
Thank You
Ramadan Kareeeem
Amr S. Moustafa
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