8/12/2019 GSD and LSD Osler Friday

1/20

GSD and LSDLouis CarrilloOsler Friday Pediatrics

8/12/2019 GSD and LSD Osler Friday

2/20

Objectives

To discuss Glycogen storage diseases presentation, deficiency,

diagnosis and treatment

To discuss Lysosomal Storage diseases presentation,

deficiency, diagnosis and treatment

Cardiac pathology associated with diseases

8/12/2019 GSD and LSD Osler Friday

3/20

LSDs

Valve dysfunction secondary to deposition of

glycosaminoglycans

Myocardial ischemia due to circumferential coronary arterial

narrowing through the entire vessel

8/12/2019 GSD and LSD Osler Friday

4/20

Hurler Disease

Deficieny in

Alpha L Iduronidase

Presents with:

Developmental delay

Gargoylism

Corneal Clouding

Hepatosplenomegaly

Cardiomyopathy from endocardial

fibroelastosis, may be seen with MR Can present in infants unlike other

Buildup of

Heparan Sulfate, dermatan sulfate

ERT

8/12/2019 GSD and LSD Osler Friday

5/20

Hunter Disease

Deficieny in

Iduronate sulfatase

Presents with:

Aggression

NO Corneal Clouding

Buildup of

Heparan sulfate and dermatan sulfate

ERT

8/12/2019 GSD and LSD Osler Friday

6/20

Fabry Disease

Deficieny in

Alpha galactosidase A

Presents with:

Angiokeratomas

Peripheral Neuropathy

LV hypertrophy; one variant limited to only heart

Buildup of

Ceramide trihexoside

Normal lifespan if treated correctly with ERT

8/12/2019 GSD and LSD Osler Friday

7/20

Krabbe Disease

Deficieny in

Galactocerebrosidase

Presents with:

Peripheral Neuropathy

Developmental Delay

Optic Atrophy

Globoid Cells which are?

Multinucleated macrophages

Buildup of Galactocerebroside

Dead baby by 2 years oldno treatment

8/12/2019 GSD and LSD Osler Friday

8/20

Gaucher Disease

Deficiency in:

Glucocerebrosidase(Beta Glucosidase)

MOST COMMON

Presents with:

Hepatosplenomegaly

Pancytopenia

Aseptic Necrosis of Femus

Buildup of

Glucocerebroside

Normal lifespan if treated correctly with ERT

8/12/2019 GSD and LSD Osler Friday

9/20

Niemann Pick Disease

Deficieny in

Sphingomyelinase

Presents with:

Hepatosplenomegaly

Neurodegeneration

Cherry Red Spot on macula

Foam Cellswhich are

Lipid Laden Macrophages

Buildup of Sphingomyelin

No treatment and dead by 2 years old but can survive to teens

depending on seveity of disease

8/12/2019 GSD and LSD Osler Friday

10/20

Tay-Sachs Disease

Deficieny in

Hexosaminidase A

Presents with:

NO Hepatosplenomegaly

Neurodegeneration

Developmental Delay

Cherry Red Spot on macula

Lysosomes with onion skin

Buildup of GM2 Ganglioside

No treatment and dead by 4

8/12/2019 GSD and LSD Osler Friday

11/20

Metachromatic

Leukodystrophy Deficieny in

Arylsulfatase A

Presents with:

Ataxia

Dementia

Peripheral and Central Demyelination

Buildup of

Cerebroside sulfate

8/12/2019 GSD and LSD Osler Friday

12/20

GSDs

15 different types

All Autosomal Recessive!! Except for which ones?? Fabry Disease

Hunter Disease

X-Linked Vacuolar Cardiomyopathy and Myopathy (Danon Disease) No longer classified as a glycogen storage because intracellular glycogen is

not always increased.

X-linked dominant defect in lysosome-associated membrane protein-2(LAMP-2) gene.

Skeletal myopathy, cardiomyopathy, conduction defects, and mentalretardation.

Males in childhood/adolescence

Females may not present until adolescence or adulthood.

Ventricular preexcitation and cardiomyopathy usually hypertrophic in malesand dilated in females.

Clusters of vacuolated myocytes suggestive of impaired autophagy.

8/12/2019 GSD and LSD Osler Friday

13/20

Pompe Disease (Type II)

Deficieny in

Lysosomal alpha 1,4 glucosidase (Acid Maltase)

Presents with:

Cardiomyopathy

Hypotonia

Increased CK and diagn

Diagnosis

Muscle Biopsy

8/12/2019 GSD and LSD Osler Friday

14/20

EKG in Pompe

8/12/2019 GSD and LSD Osler Friday

15/20

Echo in Pomp

8/12/2019 GSD and LSD Osler Friday

16/20

8/12/2019 GSD and LSD Osler Friday

17/20

Cori Disease

Deficieny in

Alpha 1,6 glucosidase

Presents with:

Mild form of Type I

Normal Lactate

Normal gluconeogenesis

Treatment is High protein diet to stimulate gluconeogenesis

8/12/2019 GSD and LSD Osler Friday

18/20

McArdle Disease

Deficieny in

Skeletal muscle glycogen

phosphorylase (myophosphorylase)

Presents with:

Elevated Muscle Glycogen

Painful Muscle Cramps

MyoglobinuriaRED Urine

Arrhythmia from electrolyte abnormalities

Renal Fail/Rhabdo with extreme exercise Diagnosis:

Muscle biopsy

8/12/2019 GSD and LSD Osler Friday

19/20

Enzyme replacement therapy

Especially useful in Gaucher, Fabry, Hunter and GSD type II,

who can lead relatively normal lives with normal lifespans if

adherent to therapy

8/12/2019 GSD and LSD Osler Friday

20/20