Dr Elio Quesada Gonzalez Consultant Pediatrician PRESENTATION OUTLINE DEFINATION EPIDEMIOLOGY HISTORICAL PERSPECTIVE CLASSIFICATION TYPES CLINICAL PRESENTATION INVESTIGATION MANAGEMENT DEFINATION ID: 931059
Download Presentation The PPT/PDF document "GLYCOGEN STORAGE DISEASE" is the property of its rightful owner. Permission is granted to download and print the materials on this web site for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.
Slide1
GLYCOGEN STORAGE DISEASE
Dr. Elio Quesada Gonzalez
Consultant Pediatrician
Slide2PRESENTATION OUTLINE
DEFINATION
EPIDEMIOLOGY
HISTORICAL PERSPECTIVE
CLASSIFICATION
TYPES
CLINICAL PRESENTATION
INVESTIGATION
MANAGEMENT.
Slide3DEFINATION
GSD ALSO KNOWN AS GLYCOGENOSIS AND DEXTRINOSIS IS A GROUP OF INHERITED DISORDERS OF METABOLISM THAT INTERFERES WITH GLYCOGEN SYNTHESIS OR BREAKDOWN IN THE LIVER, KIDNEYS, MUSCLES AND OTHER CELL TYPES.
Slide4EPIDIMIOLOGY
A STUDY IN BRITISH COLUMBIA SHOW 1/43000 LIVE BIRTH HAS SOME FORM OF GSD
A STUDY IN USA SHOWED 1/20000
NO RECORD SHOWING INCIDENCES IN RELATION TO SEXES.
Slide5HISTORICAL PERSPECTIVE
1929 A GERMAN DOCTOR EDGAR VON GIERKE PROVIDED THE INITIAL DESCRIPTION OF GSD1 IN AN AUTOPSY REPORT OF 2 CHILDREN WITH ENLARGED LIVERS CONTAINING HUGE AMOUNT OF GLYCOGEN AND SUCH WAS ALSO FOUND IN THEIR KIDNEYS.
1952 CORI&CORI REPORTED SIX SIMILAR FINDINGS IN PATIENTS WHO ALSO SHOWED DEFECIENCY IN HEPATIC GLUCOSE 6 PHOSPHATASE. GSD3
Slide6CLASSISFICATION
1. SITE OF ACTION
A. LIVER (0,I,III,IV,VI,IX)
B. MUSCLES (V, VII
C. GENERALISED (XII
2.NAME OF DISCOVERING SCIENTIST
3.NAME OF DEFICIENT ENZYME.
THERE ARE ABOUT 13 KNOWN GSD HOWEVER WE WILL MENTION 8 CLINICALLY MOST RELVANT FOR THE PURPOSE OF THIS LECTURE.
Slide7TYPES OF GSD
GSD TYPE I (VON GIERKE DISEASE)
CAUSE BY DEFICIENCY OF GLUCOSE 6 PHOSPHATASE
G6P HYDROLYSIS G6 PHOSPHATE TO GLUCOSE IN THE ER
PATIENTS ARE ABLE TO STORE GLUCOSE AS GLYCOGEN HOWEVER CANNOT RELEASE IT LEADING TO GLYCOGEN ACCOMULATION IN THE LIVER RESULTING IN HEPATOMEGALY.
Slide8PRESENTATION OF GSD 1
HEPATOMEGALY BUT NO SPLEENOMEGALY AND BILIRUBIN IS EXPECTED TO BE OK.
HYPOGLACEMIA IN FASTING AND IS A LEADING CAUSE OF HYPOTONIA AND HYPO GLACEMIA IN NEWBORNS.
HYPOGLCEMIA INHIBITS INSULIN WHICH IN TURN INHIBITS PROTEIN SYNTHESIS:::DWAFISM
HIGH LEVELS OF URIC ACID AND LACTATE DUE TO INCREASE LEVELS OF G6P CAUSING METABOLIC ACIDOSIS.
IMPAIRED GROWTH AND DELAYED PUBERTY
HYPERLIPIDEMIA DUE TO CONSTANT LOW INSULIN
Slide9KIDNEYS ARE 10 TO 20% LARGER ON USS DUE TO GLYCOGEN DEPOSITS.
NEUTOPENIA CAUSING INFECTION RISK
CLOTTING DISORDER DUE TO IMPAIRED PLATELET AGGREGATION CAUSE BY CHRONIC HYPOGLACEMIA.
OTHER SYMPTOMS INCLUDING CHRONIC HUNGER, FATIGUE, IRRITABILITY.
Slide10DIAGNOSIS/RX OF GSD I
BLOOD FOR CHRONIC HYPOGLACEMIA.
ABDOMINAL USS
LIVER FETAL BIOPSY 8 TO 22
ND
WEEK
FETAL DNA FROM CHORIONIC VILLUS SAMPLING
GENETICS TESTING (AUTOSOMAL RECESSIVE)
BABIES ARE TREATED BY GIVING GLUCOSE AND OLDER CHILDREN ARE GIVEN CORNSTATCH.
Slide11GSD TYPE II
POMPE DISEASE
IS AN AUTOSOMAL RECESSIVE METABOLIC DISORDER WHICH DAMAGES MUSCLE AND NERVES CELLS THROUGHOUT THE BODY
THE ONLY LYSOSOMAL RELATED GSD
CAUSE BY DEFICIENCY OF ACID ALPHA-GLUCOSIDASE LYSOSOMAL ENZYME
THIS ENZYME DEGRADES ALPHA 1,4 AND 1,6 LINKAGES IN GLYCOGEN,MALTOSE SO DEFICIENCY LEADS TO ACCOMULATION OF GLYCOGEN IN LYSOSOMES AND CYTOPLASM
Slide12PRESENTATION
NO HYPOGLACEMIA OR HYPERLIPIDEMIA LIKE THOSE IN GSD I
THERE IS HEPATOMEGALY
MAIN PRESENTATION IS CARDIOMEGALY (92% AND CARDIOMYOPATHY LEADING TO HEART FAILURE AND MUSCLE WEAKNESS.
FEEDING DIFFICULTIES AND FAILURE TO THRI
MACROGLOSSIA WITH WIDE OPEN MOUTH AND EYES,NASAL FLARING AND RESPIRATORY DISTRESS
DEATH BY AGE 2YRS FOR INFANTILE VARIANT
Slide13LATE ONSET FEATURES INCLUDES IMPAIRED COUGH,RECURRENT CHEST INFECTION
REDUCED VITAL CAPACITY
HYPOTONIA
SWALLOWING AND CHEWING DIFF.
LESS CARDIAC INVOLVEMENT(MAIN DIFFERENCE FROM INFANTILE VARIANT.
Slide14DIAGNOSIS/RX
MUSCLE OR SKIN BIOPSY TO ESTIMATE ACID ALPHA GLUCOSIDASE ACTIVITY.
SERUM CREATININE KINASE INCREASE BY 10 FOLDS WITH LESS ELEVATION IN LIVER ENZYME
ECG SHOW CARDIOMEGALY WITH NO SPECIFIC CONDUCTION DEFECTS.
MYOZYME APPROVED IN 2006 AS AN ENZYME REPLACEMENT
THERAPY.(INFANTILE ONSET
LUMIZYME (FOR LATE ONSET
Slide15GSD TYPE III
CORI- FORBES DISEASE
IS A DEFICIENCY OF DEBRANCHING ENZYME (AMYLO 1,6 GLUCOSIDASE) LEADING TO ACCOMULATION OF DEXTRIN LIKE STRUCTURES IN THE CYTOPLASM.
IT HAS BEEN CLASSIFIED
IIIA MOST COMMON AFFECTS LIVER/MUSCLE
IIIB AFFECTS LIVER ONLY NO MUSCLE
SYMPTOMS ARE A COMBINATION OF BOTH GSDI AND GSD II.
Slide16DIAGNOSIS/RX
LIVER AND MUSCLE BIOPSY
ULTRASOUND
DNA MUTATION ANALYSIS
RX WITH HIGH PROTEIN DIET FACILITATE GLUCONEOGENESIS
GLUCOSE IV OR ORAL
VIT D
LIVER TRANSPLANT
Slide17OTHER KNOWN GSD
GSD TYPE IV AMYLOPECTINOSIS (ANDERSON DISEASE ) IS A BRANCHING ENZYME DISORDER,
MOST ASSOCIATED WITH LIVER CIRRHOSIS
FAILURE TO THRIVE
NO HYPOGLACEMIA OR HYPER LIPIDEMIA.
NO MUSCLE SYMPTOMS
DEATH BY AGE 5
Slide18GSD TYPE V (
McARDLE’S
DISEASE)
DEFICIENT IN MUSCLE GLYCOGEN PHOSPHORYLASE.
PAY ATTENTION TO MUSCLE CRAMPS IN EXERCISE AND BURGUNDY COLOURED URINE.
EXERCISE INDUCED RHABDOMYOLYSIS
RENAL FAILURE COMMONEST CAUSE OF DEATH.
Slide19GSD TYPE VI (HERS’ DISEASE)
DEFICIENT IN LIVER GLYCOGEN PHOSPHORYLASE
HAS THE PRESENTATION OF HYPOGLACEMIA, HYPERLIPIDEMIA AND HEPATOMEGALY.
GSD TYPE VII (TARUL’S DISEASE)
DEFICIENT IN MUSCLE PHOSPHO FRUCTOKINASE
EXERCISE INDUCED CRAMPS,GROWTH RETARDATION AND HAEMOLYTIC ANAEMIA
Slide20GSD TYPE IX
DEFICIENT IN PHOSPHORYLASE KINASE
IS A LIVER RELATED GSD AND LEADS TO ALL THE LIVER PRESENTATIONS AND DELAYED MOTOR WITH GROWTH RETARDATION.
TAKE HOME FOR PRESENTATION
GSD TYPE 1 VON GIERKE DISEASE IS THE COMMONEST
HYPOTONIA AND HYPOGLACEMIA IN NEWBORN PLS THINK OF GSD 1
MUSCLE CRAMPS,EXERCISE INTOLERANCE AND HAEMOLYTIC ANAEMIA ESPECIALLY IF SICKLE NEGATIVE THINK GSD
TISSUE BIOPSY REMAINS THE BEST DIAGNOSTIC TOOL
RAPAMYCIN TO INDUCE AUTOPHAGY
Slide22REFERENCES
WWW.SCIENCEDAILY.COM
WWW.WIKIPEDIA.ORG/GLYCOGEN
EMEDICINE.MEDSCAPE.COM
THANKS.