Transcript
Page 1: Evaluation of Plasma Selenium Level, Glutathione Peroxidase Activity and Thyroid Functions in Children with Phenylketonuria Evaluation of Plasma Selenium
Page 2: Evaluation of Plasma Selenium Level, Glutathione Peroxidase Activity and Thyroid Functions in Children with Phenylketonuria Evaluation of Plasma Selenium

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

Page 3: Evaluation of Plasma Selenium Level, Glutathione Peroxidase Activity and Thyroid Functions in Children with Phenylketonuria Evaluation of Plasma Selenium

PhenylketonuriaPhenylketonuria

Autosomal Recessive

Unless Treated, Irreversible MR

Newborn Screening

Autosomal Recessive

Unless Treated, Irreversible MR

Newborn Screening

Page 4: Evaluation of Plasma Selenium Level, Glutathione Peroxidase Activity and Thyroid Functions in Children with Phenylketonuria Evaluation of Plasma Selenium

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

Page 5: Evaluation of Plasma Selenium Level, Glutathione Peroxidase Activity and Thyroid Functions in Children with Phenylketonuria Evaluation of Plasma Selenium

Natural AntioxidantsNatural Antioxidants

Enzymes• Superoxide Dismutase• Catalase• Glutathione Peroxidase

Vitamins and Trace-elements • Water-Soluble: Vitamin C• Fat-Soluble: Vitamin A and E• Selenium

Page 6: Evaluation of Plasma Selenium Level, Glutathione Peroxidase Activity and Thyroid Functions in Children with Phenylketonuria Evaluation of Plasma Selenium

Oxidative StressOxidative Stress

The Imbalance between

ROS

Natural Antioxidants

The Imbalance between

ROS

Natural Antioxidants

Page 7: Evaluation of Plasma Selenium Level, Glutathione Peroxidase Activity and Thyroid Functions in Children with Phenylketonuria Evaluation of Plasma Selenium

Glutathione Peroxidase (GPX)

Glutathione Peroxidase (GPX)

• GPX Gene on Chromosome 3• GPX is a Selenoprotein

GSSG

GSHH2O2

H2OGPX

NADPH+H+

NADP+

PPP

Page 8: Evaluation of Plasma Selenium Level, Glutathione Peroxidase Activity and Thyroid Functions in Children with Phenylketonuria Evaluation of Plasma Selenium

Selenium (Se)Selenium (Se)

• Essential MicronutrientRDA and RNI

• Selenoproteins

• FunctionsAntioxidant Formation of Active T3Immune System Blood Clotting

GPX, Iodothyronine Deiodinase, …

Page 9: Evaluation of Plasma Selenium Level, Glutathione Peroxidase Activity and Thyroid Functions in Children with Phenylketonuria Evaluation of Plasma Selenium

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

Page 10: Evaluation of Plasma Selenium Level, Glutathione Peroxidase Activity and Thyroid Functions in Children with Phenylketonuria Evaluation of Plasma Selenium

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

Page 11: Evaluation of Plasma Selenium Level, Glutathione Peroxidase Activity and Thyroid Functions in Children with Phenylketonuria Evaluation of Plasma Selenium

Age DistributionAge Distribution

0

1

2

3

4

5

6

7

8

9A

ge

( year

s

)

Cases Control

Page 12: Evaluation of Plasma Selenium Level, Glutathione Peroxidase Activity and Thyroid Functions in Children with Phenylketonuria Evaluation of Plasma Selenium

0%

10%

20%

30%

40%

50%

60%P

erce

nt

of

case

s

Cases Control

Males Females

Sex Distribution Sex Distribution

Page 13: Evaluation of Plasma Selenium Level, Glutathione Peroxidase Activity and Thyroid Functions in Children with Phenylketonuria Evaluation of Plasma Selenium

Consanguinity among PKU

Consanguinity among PKU

Consanguinity

Yes72%

No28%

Page 14: Evaluation of Plasma Selenium Level, Glutathione Peroxidase Activity and Thyroid Functions in Children with Phenylketonuria Evaluation of Plasma Selenium

Family History among PKU

Family History among PKUFamily History

Positive50%

Negative50%

Page 15: Evaluation of Plasma Selenium Level, Glutathione Peroxidase Activity and Thyroid Functions in Children with Phenylketonuria Evaluation of Plasma Selenium

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

Page 16: Evaluation of Plasma Selenium Level, Glutathione Peroxidase Activity and Thyroid Functions in Children with Phenylketonuria Evaluation of Plasma Selenium

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

Page 17: Evaluation of Plasma Selenium Level, Glutathione Peroxidase Activity and Thyroid Functions in Children with Phenylketonuria Evaluation of Plasma Selenium

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 %

Page 18: Evaluation of Plasma Selenium Level, Glutathione Peroxidase Activity and Thyroid Functions in Children with Phenylketonuria Evaluation of Plasma Selenium

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

Page 19: Evaluation of Plasma Selenium Level, Glutathione Peroxidase Activity and Thyroid Functions in Children with Phenylketonuria Evaluation of Plasma Selenium

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)

Page 20: Evaluation of Plasma Selenium Level, Glutathione Peroxidase Activity and Thyroid Functions in Children with Phenylketonuria Evaluation of Plasma Selenium

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)

Page 21: Evaluation of Plasma Selenium Level, Glutathione Peroxidase Activity and Thyroid Functions in Children with Phenylketonuria Evaluation of Plasma Selenium

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

Page 22: Evaluation of Plasma Selenium Level, Glutathione Peroxidase Activity and Thyroid Functions in Children with Phenylketonuria Evaluation of Plasma Selenium

• 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)

Page 23: Evaluation of Plasma Selenium Level, Glutathione Peroxidase Activity and Thyroid Functions in Children with Phenylketonuria Evaluation of Plasma Selenium

Thank You

Ramadan Kareeeem

Amr S. Moustafa


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