GLYCOGEN STORAGE DISEASE - PowerPoint Presentation

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GLYCOGEN STORAGE DISEASE

Dr. Elio Quesada Gonzalez

Consultant Pediatrician

PRESENTATION OUTLINE

DEFINATION

EPIDEMIOLOGY

HISTORICAL PERSPECTIVE

CLASSIFICATION

TYPES

CLINICAL PRESENTATION

INVESTIGATION

MANAGEMENT.

DEFINATION

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.

EPIDIMIOLOGY

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.

HISTORICAL 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

CLASSISFICATION

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.

TYPES 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.

PRESENTATION 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

KIDNEYS 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.

DIAGNOSIS/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.

GSD 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

PRESENTATION

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

LATE ONSET FEATURES INCLUDES IMPAIRED COUGH,RECURRENT CHEST INFECTION

REDUCED VITAL CAPACITY

HYPOTONIA

SWALLOWING AND CHEWING DIFF.

LESS CARDIAC INVOLVEMENT(MAIN DIFFERENCE FROM INFANTILE VARIANT.

DIAGNOSIS/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

GSD 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.

DIAGNOSIS/RX

LIVER AND MUSCLE BIOPSY

ULTRASOUND

DNA MUTATION ANALYSIS

RX WITH HIGH PROTEIN DIET FACILITATE GLUCONEOGENESIS

GLUCOSE IV OR ORAL

VIT D

LIVER TRANSPLANT

OTHER 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

GSD 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.

GSD 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

GSD 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

REFERENCES

WWW.SCIENCEDAILY.COM

WWW.WIKIPEDIA.ORG/GLYCOGEN

EMEDICINE.MEDSCAPE.COM

THANKS.