Glycogen storage disorders
- Caused due to genetic defects that result in def. of certain enzymes of glycogen metabolism resulting
in Ab N Glycogen metabolism & accumulation of Glycogen within cells.
- Periodic-acid schiff (PAS) identifies glycogen and useful for identifying these conditions.
Type Ia (Von : - Deficiency of Glucose-6-Phosphatase
Gierke Disease) - Severe fasting hypoglycaemia, Gly. In liver & kidneys, Blood lactate, Triglyceri-
des, Uric acid(Gout),ketosis, & hepatomegaly, renogmegaly. Liver does not regulate
blood glucose. Impaired Gluconeogenesis and glycogenolysis.
- Treatment : Frequent oral glucose/cornstarch; avoidance of fructose and galactose.
Type Ib : - Deficiency of ER Glucose-6-Phosphatase transporter.
- Neutropenia & recurrent infections, rest as type 1a.
Type II (Pompe’s : - Def. Of Lysosomal Alpha-1,4(acid maltase) & 1,6 glucosidase.
Disease) - Fatal, accumulation of glycogen in lysosomes, heart failure, cardiomyopathy,
hypotonia, exercise intolerance.
Type III (Cori’s : - Def. of Debranching enzymes(alpha-1,4 glucosidase & 4-alp- glucanotransferase).
Disease) - similar to Von Gierke, but milder symp. , N blood lactate levels, can lead to card-
iomyopathy, limit dextrin-like structures accumulate in cytosol.
- Gluconeogenesis is intact, Accumulation of characteristic branched polysaccharide.
Type IV (Andersen : - Def. Of Branching enzyme. Neuromuscular form can present at any age.
Disease) - Hypoglycaemia occurs late, most commonly presents as hepatosplenomegaly &
failure to thrive in early infancy. Infantile cirrhosis, muscular weakness, hypoto-
nia, cardiomyopathy, early childhood death.
Type V (McArdle : - Def. of skeletal muscle glycogen phosphorylase(myophosphorylase).
Syndrome) - Characterized by flat venous lactate curve c N in ammonia levels during exe-
rcise. Gly. in muscle, but ms. can’t break it down = painful muscle cramps,
Type I-V are Myoglobinuria(red urine) c strenuous exercise, & arrhythmia from elec- ab N .
Autosomal Second-wind phenomena noted during exercise due to Muscular blood flow.
Recessive - Blood glucose levels typing unaffected.
Andersen = Branching ; Cori = Debranching (ABCD).
Type VI (Her’s Disease) - Def. Of liver phosphorylase, high Gly. In liver, can cause hypoglycaemia.
Type VII (Tarui’s disease) - Def. Of Musclephosphofructokinase. Features similar to type V.
Type VIII - Def. of phosphorylasekinase.
Type IX - Def. of muscle & liver phosphorylasekinase Leads to Hepatomegaly
Type X - Def. of cAMP dependent protein kinase A
, Lysosomal storage disorders
Sphingolipidoses Mucopolysaccharidoses
IV) Krabbe disease :
I) Tay-Sachs Disease : I) Hurler syndrome :
Autosomal Recessive Autosomal recessive
Def. of Hexosaminidase A Def. of galactocerebrosidase(galactosylceramidase) Autosomal recessive
Accumulation of galactocerebrosidase, psychosine.
Accumulation of GM ganglioside
Source : First aid textbook
Deficiency of -L-iduronidase
- Progressive neurodegeneration
- Peripheral neuropathy
-Developmental delay - destruction of oligodendrocytes
Findings : - Developmental delay
- Hyperreflexia - Developmental delay
Findings : - Cherry red spot on macula d/t - Optic atrophy - Airway obstruction
lipid accumu. In ganglion cell - globoid cells Findings : - Skeletal abnormalities
layer
- Corneal clouding
- lysosomes with onion skin
- No hepatosplenomegaly
V) Gaucher disease : - Hepatosplenomegaly
Autosomal recessive
Def. of Glucocerebrosidase( -glucosidase) ;
I) Fabry disease : R c recombinant glucocerebrosidase
X linked recessive Accumulation of Glucocerebroside Gaucher cell II) Hunter syndrome :
Source : First aid textbook
Def. of -galactosidase A - Bone crisis
Accumu. of Ceramide tri-hexosi-
- Most commonly found
- Gaucher cells (lipid laden
X-linked Recessive
Findings : - Hepatosplenomegaly
dase(globoriaosylceramide) Angiokeratomas
Source : First aid textbook
- Pancytopenia macrophages resembling Deficiency of Iduronate-2-sulfatase
- AVN of femur tissue paper appearance)
Early : TRIAD of
- episodic peripheral neuropathy
- Angiokeratomas
VI) Niemann-Pick Disease : - Mild hurler
Autosomal recessive
Findings : - Hypohidrosis Def. of Sphingomyelinase +
Late : Findings :
- Progressive renal failure
Accumulation of sphingomyelin
Foam cell
Source : First aid textbook
Aggressive behaviour
- Cardiovascular disease - Progressive neurodegeneration
Findings : - Hepatosplenomegaly
III) Metachromatic leukodystrophy :
Autosomal recessive
- Foam cells (lipid laden macrophages - no corneal clouding
- Cherry red spot on macula
Def. of Arylsulfatase A
Accumulation of Cerebroside sulfate
GM GM Ceramide trihexoside
Central and peripheral Accumulated substrate in both syndromes :
Findings : demyelination c ataxia Sulfatides Glucocerebroside
and dementia. Galactocerebrosidase Ceramide Sphingomyelin
- Heparan and dermatan sulfate
- Caused due to genetic defects that result in def. of certain enzymes of glycogen metabolism resulting
in Ab N Glycogen metabolism & accumulation of Glycogen within cells.
- Periodic-acid schiff (PAS) identifies glycogen and useful for identifying these conditions.
Type Ia (Von : - Deficiency of Glucose-6-Phosphatase
Gierke Disease) - Severe fasting hypoglycaemia, Gly. In liver & kidneys, Blood lactate, Triglyceri-
des, Uric acid(Gout),ketosis, & hepatomegaly, renogmegaly. Liver does not regulate
blood glucose. Impaired Gluconeogenesis and glycogenolysis.
- Treatment : Frequent oral glucose/cornstarch; avoidance of fructose and galactose.
Type Ib : - Deficiency of ER Glucose-6-Phosphatase transporter.
- Neutropenia & recurrent infections, rest as type 1a.
Type II (Pompe’s : - Def. Of Lysosomal Alpha-1,4(acid maltase) & 1,6 glucosidase.
Disease) - Fatal, accumulation of glycogen in lysosomes, heart failure, cardiomyopathy,
hypotonia, exercise intolerance.
Type III (Cori’s : - Def. of Debranching enzymes(alpha-1,4 glucosidase & 4-alp- glucanotransferase).
Disease) - similar to Von Gierke, but milder symp. , N blood lactate levels, can lead to card-
iomyopathy, limit dextrin-like structures accumulate in cytosol.
- Gluconeogenesis is intact, Accumulation of characteristic branched polysaccharide.
Type IV (Andersen : - Def. Of Branching enzyme. Neuromuscular form can present at any age.
Disease) - Hypoglycaemia occurs late, most commonly presents as hepatosplenomegaly &
failure to thrive in early infancy. Infantile cirrhosis, muscular weakness, hypoto-
nia, cardiomyopathy, early childhood death.
Type V (McArdle : - Def. of skeletal muscle glycogen phosphorylase(myophosphorylase).
Syndrome) - Characterized by flat venous lactate curve c N in ammonia levels during exe-
rcise. Gly. in muscle, but ms. can’t break it down = painful muscle cramps,
Type I-V are Myoglobinuria(red urine) c strenuous exercise, & arrhythmia from elec- ab N .
Autosomal Second-wind phenomena noted during exercise due to Muscular blood flow.
Recessive - Blood glucose levels typing unaffected.
Andersen = Branching ; Cori = Debranching (ABCD).
Type VI (Her’s Disease) - Def. Of liver phosphorylase, high Gly. In liver, can cause hypoglycaemia.
Type VII (Tarui’s disease) - Def. Of Musclephosphofructokinase. Features similar to type V.
Type VIII - Def. of phosphorylasekinase.
Type IX - Def. of muscle & liver phosphorylasekinase Leads to Hepatomegaly
Type X - Def. of cAMP dependent protein kinase A
, Lysosomal storage disorders
Sphingolipidoses Mucopolysaccharidoses
IV) Krabbe disease :
I) Tay-Sachs Disease : I) Hurler syndrome :
Autosomal Recessive Autosomal recessive
Def. of Hexosaminidase A Def. of galactocerebrosidase(galactosylceramidase) Autosomal recessive
Accumulation of galactocerebrosidase, psychosine.
Accumulation of GM ganglioside
Source : First aid textbook
Deficiency of -L-iduronidase
- Progressive neurodegeneration
- Peripheral neuropathy
-Developmental delay - destruction of oligodendrocytes
Findings : - Developmental delay
- Hyperreflexia - Developmental delay
Findings : - Cherry red spot on macula d/t - Optic atrophy - Airway obstruction
lipid accumu. In ganglion cell - globoid cells Findings : - Skeletal abnormalities
layer
- Corneal clouding
- lysosomes with onion skin
- No hepatosplenomegaly
V) Gaucher disease : - Hepatosplenomegaly
Autosomal recessive
Def. of Glucocerebrosidase( -glucosidase) ;
I) Fabry disease : R c recombinant glucocerebrosidase
X linked recessive Accumulation of Glucocerebroside Gaucher cell II) Hunter syndrome :
Source : First aid textbook
Def. of -galactosidase A - Bone crisis
Accumu. of Ceramide tri-hexosi-
- Most commonly found
- Gaucher cells (lipid laden
X-linked Recessive
Findings : - Hepatosplenomegaly
dase(globoriaosylceramide) Angiokeratomas
Source : First aid textbook
- Pancytopenia macrophages resembling Deficiency of Iduronate-2-sulfatase
- AVN of femur tissue paper appearance)
Early : TRIAD of
- episodic peripheral neuropathy
- Angiokeratomas
VI) Niemann-Pick Disease : - Mild hurler
Autosomal recessive
Findings : - Hypohidrosis Def. of Sphingomyelinase +
Late : Findings :
- Progressive renal failure
Accumulation of sphingomyelin
Foam cell
Source : First aid textbook
Aggressive behaviour
- Cardiovascular disease - Progressive neurodegeneration
Findings : - Hepatosplenomegaly
III) Metachromatic leukodystrophy :
Autosomal recessive
- Foam cells (lipid laden macrophages - no corneal clouding
- Cherry red spot on macula
Def. of Arylsulfatase A
Accumulation of Cerebroside sulfate
GM GM Ceramide trihexoside
Central and peripheral Accumulated substrate in both syndromes :
Findings : demyelination c ataxia Sulfatides Glucocerebroside
and dementia. Galactocerebrosidase Ceramide Sphingomyelin
- Heparan and dermatan sulfate
