Glycogen storage disease type II

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Anmol Pitliya, M.B.B.S. M.D.[2]

Glycogen storage disease type 2 (GSD type 2) results due to deficiency of lysosomal enzyme acid α-glucosidase (GAA). GSD type 2 is the most severe type of GSD leading to death in earlier stages of life. Deficiency of GAA leads to accumulation of glycogen in lysosomes of various tissues, most commonly in cardiac, skeletal, and smooth muscle cells. There is a progressive accumulation of glycogen and its substrates in tissues leading to debilitation, organ failure and finally death. GSD type 2 follows an autosomal recessive pattern. GAA gene mutation responsible for lysosomal enzyme acid α-glucosidase (GAA) deficiency in GSD type 2 and is located on chromosome locus 17q25. Glycogen storage disease type II may be classified according to the age of onset and presence of cardiomegaly into 2 subtypes including infantile-onset Pompe disease (IOPD) and late-onset Pompe disease (LOPD). According to the Recommended Uniform Screening Panel for newborn screening, screening for glycogen storage disease type 2 by Liquid Chromatography-Tandem Mass Spectrometry assay of leukocyte acid α-glucosidase is recommended for newborn. The symptoms of classic infantile glycogen storage disease type 2 (GSD type 2) usually develop in the first two months of life and start with symptoms of feeding difficulties and failure to thrive. If left untreated, patients with classic infantile GSD type 2 progress to cardiac failure resulting in death within first two years of life. Most common cause of mortality in late onset glycogen storage disease type 2 is respiratory failure followed by ruptured cerebral aneurysm. Patients with glycogen storage disease type 2 (GSD type 2) may have a positive history of GSD type 2 in family members, delay in developmental milestones, infant slips through when grasped under the arms, respiratory difficulties, frequent respiratory infections, and cardiac symptoms. Most common symptoms of infantile onset glycogen storage disease type 2 include hypotonia and muscle weakness. Most common symptoms of late onset glycogen storage disease type 2 include progressive muscle weakness, swallowing difficulties, ans respiratory problems.Physical examination of patients with glycogen storage disease type 2 (GSD type 2) is usually remarkable for muscular weakness, hypotonia, absent deep tendon reflex and paucity of movements. Patients with infantile GSD type 2 usually appear dyspneic, pale, and/or cyanotic. Acid α-glucosidase (GAA) activity in fibroblast of a dried blood sample is the gold standard test for the diagnosis of glycogen storage disease type 2. Decreased activity of GAA in fibroblasts a dried blood sample is confirmatory of glycogen storage disease type 2. Pharmacologic medical therapy is recommended among patients with infantile onset glycogen storage type 2 (GSD type 2). Pharmacologic medical therapies for GSD type 2 include enzyme replacement therapy (ERT) with recombinant human acid alpha-glucosidase.

In 1932, J.C. Pompe, a Dutch pathologist described “idiopathic hypertrophy of the heart” as a post-mortem finding in a 7-month-old girl. This was later confirmed as glycogen storage disease type 2. In 2006, enzyme replacement therapy (ERT) with recombinant human acid alpha-glucosidase (rhGAA, alglucosidase alpha) was approved by the US Food and Drug Administration (FDA) for patients with infantile-onset GSD type 2.

Glycogen storage disease type II may be classified according to the age of onset and presence of cardiomegaly into 2 subtypes including infantile-onset Pompe disease (IOPD) and late-onset Pompe disease (LOPD).

Glycogen storage disease type 2 (GSD type 2) results due to deficiency of lysosomal enzyme acid α-glucosidase (GAA). GSD type 2 is the most severe type of GSD leading to death in earlier stages of life. Deficiency of GAA leads to accumulation of glycogen in lysosomes of various tissues, most commonly in cardiac, skeletal, and smooth muscle cells. There is a progressive accumulation of glycogen and its substrates in tissues leading to debilitation, organ failure and finally death. GSD type 2 follows an autosomal recessive pattern. GAA gene mutation responsible for lysosomal enzyme acid α-glucosidase (GAA) deficiency in GSD type 2 and is located on chromosome locus 17q25. On gross pathology, characteristic findings of glycogen storage disease type 2 include cardiomegaly and myopathy. On microscopic histopathological analysis, characteristic findings of glycogen storage disease type 2 include muscle has PAS-positive (diastase sensitive) vacuoles.

Glycogen storage disease type 2 is an autosomal recessive disorder. Glycogen storage disease type 2 is caused by the deficiency of the lysosomal acid alpha-1,4-glucosidase enzyme. GAA gene responsible for the lysosomal acid alpha-1,4-glucosidase enzyme deficiency is located on chromosome 17q25.

Infantile onset glycogen storage disease type 2 (GSD type 2) must be differentiated from other diseases on the basis of characteristics including hypotonia, myopathy, dyspnea, feeding diffculties, absent reflex, macroglossia, hepatomegaly, heart failure, elevated CK, and cardiomegaly. Infantile onset glycogen storage disease should be differentiated from glycogen storage disease type 3, glycogen storage disease type 4, acute Werdnig-Hoffman disease (spinal muscular atrophy), hypothyroidism, endocardial fibroelastosis, myocarditis, congenital muscular dystrophy, mitochondrial/respiratory chain disorder, peroxisomal disorders. Late onset glycogen storage disease type 2 (GSD type 2) must be differentiated from other diseases on the basis of characteristics including hypotonia, muscle weakness, respiratory imapirement, difficulty in walking, hepatomegaly, elevated CK, and cardiomyopathy. Late onset glycogen storage disease should be differentiated from glycogen storage disease type 3, glycogen storage disease type 4, limb girdle muscle atrophy (LGMD), Becker muscular dystrophy (BMD), scapuloperonral syndromes, mitochondrial myopathies, myasthenia gravis, spinal muscular atrophy, polymyositis.

The incidence of glycogen storage disease type 2 (GSD type 2) is approximately 2.5 per 100,000 individuals. Patients of all age groups may develop glycogen storage disease type 2. However, glycogen storage disease type 2 most commonly affects individuals younger than 1 year of age. Glycogen storage disease type 2 usually affects individuals of the Caucasian race.

The most potent risk factor in the development of glycogen storage disease type 2 is a sibling with glycogen storage disease type 2.

According to the Recommended Uniform Screening Panel for newborn screening, screening for glycogen storage disease type 2 by Liquid Chromatography-Tandem Mass Spectrometry assay of leukocyte acid α-glucosidase is recommended for newborn.

The symptoms of classic infantile glycogen storage disease type 2 (GSD type 2) usually develop in the first two months of life and start with symptoms of feeding difficulties and failure to thrive. If left untreated, patients with classic infantile GSD type 2 progress to cardiac failure resulting in death within first two years of life. Most common cause of mortality in late onset glycogen storage disease type 2 is respiratory failure followed by ruptured cerebral aneurysm. Common complications of glycogen storage disease type 2 include cardiomegaly, cardiomyopathy, respiratory failure, respiratory infections, and cerebral aneurysm. Depending on the age of onset of glycogen storage disease type 2, the prognosis may vary. The prognosis is comparatively better as the age of onset increases. The presence of classic infantile GSD type 2 is associated with an extremely poor prognosis and the majority of the patients are on ventilator support by a median age of 5.9 months with a median age of death at 8.7 months. Childhood/juvenile GSD type 2 have a relatively good prognosis. Patients may survive up to the third decade of life.

Acid α-glucosidase (GAA) activity in fibroblast of a dried blood sample is the gold standard test for the diagnosis of glycogen storage disease type 2. Decreased activity of GAA in fibroblasts a dried blood sample is confirmatory of glycogen storage disease type 2.

Patients with glycogen storage disease type 2 (GSD type 2) may have a positive history of GSD type 2 in family members, delay in developmental milestones, infant slips through when grasped under the arms, respiratory difficulties, frequent respiratory infections, and cardiac symptoms. Most common symptoms of infantile onset glycogen storage disease type 2 include hypotonia and muscle weakness. Most common symptoms of late onset glycogen storage disease type 2 include progressive muscle weakness, swallowing difficulties, ans respiratory problems.

Physical examination of patients with glycogen storage disease type 2 (GSD type 2) is usually remarkable for muscular weakness, hypotonia, absent deep tendon reflex and paucity of movements. Patients with infantile GSD type 2 usually appear dyspneic, pale, and/or cyanotic.

Laboratory findings consistent with the diagnosis of glycogen storage disease type 2 (GSD type 2) include elevated CK, elevated CK-MB, elevated LDH, elevated liver aminotransferases, elevated urinary glc 4, and deficiency of α-glucosidase in fibroblasts, leukocytes, and/or in muscle tissue.

An ECG may be helpful in the diagnosis of glycogen storage disease type 2 (GSD type 2). Findings on an ECG suggestive of GSD type 2 include short PR interval, tall QRS, and left ventricular hypertrophy.

There are no X-ray findings associated with glycogen storage disease type 2 (GSD type 2). However, an X-ray may be helpful in the diagnosis of the cardiac complication of GSD type 2, which include cardiomegaly.

There are no CT scan findings associated with glycogen storage disease type 2 (GSD type 2). However, a CT scan may be helpful in the diagnosis of neurological complications of GSD type 2, which include possible widening of the anterior horn of the lateral ventricle and/or peripheral liquor spaces.

There are no MRI findings associated with glycogen storage disease type 2 (GSD type 2). However, an MRI may be helpful in the diagnosis of neurologic complications of GSD type 2, which include central and cortical atrophy.

An echocardiography may be helpful in the diagnosis of cardiac complications of glycogen storage disease type 2 (GSD type 2). Findings for infantile GSD type 2 include cardiomegaly and findings for late onset GSD type 2 include dilated cardiomyopathy.

Dual energy X-ray absorptiometry (DXA) may be helpful in the diagnosis of osteoporosis, osteopenia, and/or fracture in patients with glycogen storage disease type 2. Findings on an dual energy X-ray absorptiometry suggestive of osteoporosis and/or osteopenia in patients with glycogen storage disease type 2 include low bone mineral density (BMD).

Other diagnostic studies for glycogen storage disease type 2 (GSD type 2) include electromyography and molecular genetic testing. Electromyography findings suggestive of GSD type 2 include myopathy.

Pharmacologic medical therapy is recommended among patients with infantile onset glycogen storage type 2 (GSD type 2). Pharmacologic medical therapies for GSD type 2 include enzyme replacement therapy (ERT) with recombinant human acid alpha-glucosidase.

Surgical intervention is not recommended for the management of glycogen storage disease type 2.

Effective measures for primary prevention of glycogen storage disease type 2 (GSD type 2) include genetic counselling, prenatal diagnosis, and screening.

Effective measures for the secondary prevention of glycogen storage disease type 2 (GSD type 2) include general medical recommendations, cardiology recommendations, pulmonary recommendations, gastrointestinal/nutritional recommendations, musculoskeletal/functional/rehabilitation recommendations, neurological recommendations., and surgery/anesthesia recommendations.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Anmol Pitliya, M.B.B.S. M.D.[2]

In 1932, J.C. Pompe, a Dutch pathologist described “idiopathic hypertrophy of the heart” as a post-mortem finding in a 7-month-old girl. This was later confirmed as glycogen storage disease type 2. In 2006, enzyme replacement therapy (ERT) with recombinant human acid alpha-glucosidase (rhGAA, alglucosidase alpha) was approved by the US Food and Drug Administration (FDA) for patients with infantile-onset GSD type 2.

• Glycogen storage disease type 2 (GSD type 2) is the first storage disease to be described due to lysosome enzyme defect.
• In 1932, J.C. Pompe, a Dutch pathologist described “idiopathic hypertrophy of the heart” as a post-mortem finding in a 7-month-old girl. This was later confirmed as glycogen storage disease type 2.^[1]
• In 1954, G.T. Cori classified pompe disease as glycogen storage disease type 2.^[2][3]
• In 1963, H.G. Hers described that GSD type 2 is due to generalized deficiency of lysosomal enzyme acid α-glucosidase (GAA).^[4]

• In 2006, enzyme replacement therapy (ERT) with recombinant human acid alpha-glucosidase (rhGAA, alglucosidase alpha) was approved by the US Food and Drug Administration (FDA) for patients with infantile-onset GSD type 2.^[5]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Anmol Pitliya, M.B.B.S. M.D.[2]

Glycogen storage disease type II may be classified according to the age of onset and presence of cardiomegaly into 2 subtypes including infantile-onset Pompe disease (IOPD) and late-onset Pompe disease (LOPD).

Glycogen storage disease type II may be classified according to the age of onset and presence of cardiomegaly into 2 subtypes:^{[1][2][3][4][5]}

Type of GSD type 2		Age of onset
Infantile-onset Pompe disease (IOPD)	Classic form	Age of onset before 12 months with cardiomyopathy
	Non-Classic form
Late-onset Pompe disease (LOPD)	Childhood/Juvenile form	Age of onset before 12 months without cardiomyopathy Age of onset after 12 months
	Adult form

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Anmol Pitliya, M.B.B.S. M.D.[2]

Glycogen storage disease type 2 (GSD type 2) results due to deficiency of lysosomal enzyme acid α-glucosidase (GAA). GSD type 2 is the most severe type of GSD leading to death in earlier stages of life. Deficiency of GAA leads to accumulation of glycogen in lysosomes of various tissues, most commonly in cardiac, skeletal, and smooth muscle cells. There is a progressive accumulation of glycogen and its substrates in tissues leading to debilitation, organ failure and finally death. GSD type 2 follows an autosomal recessive pattern. GAA gene mutation responsible for lysosomal enzyme acid α-glucosidase (GAA) deficiency in GSD type 2 and is located on chromosome locus 17q25. On gross pathology, characteristic findings of glycogen storage disease type 2 include cardiomegaly and myopathy. On microscopic histopathological analysis, characteristic findings of glycogen storage disease type 2 include muscle has PAS-positive (diastase sensitive) vacuoles.

• Glycogen storage disease type 2 (GSD type 2) results due to deficiency of lysosomal enzyme acid α-glucosidase (GAA).^[1]
• GSD type 2 is the most severe type of GSD leading to death in earlier stages of life.
• Deficiency of GAA leads to accumulation of glycogen in lysosomes of various tissues, most commonly in cardiac, skeletal, and smooth muscle cells.^[2]
• There is a progressive accumulation of glycogen and its substrates in tissues leading to debilitation, organ failure and finally death.^[3]
• There are a range of severity and varies with:
  • Age of onset
  • Organ involvement including degree and severity of muscular involvement (skeletal, respiratory, cardiac)
  • Rate of progression
• It is believed that movement of muscle and increased myofibril rigidity during contraction leads to rupture of lysosomes in muscle. These ruptured lysosomes in muscles releases glycogen and other lysosomal contents leading to destruction of muscles.^[4]
• Other cells including marcophages also deposits glycogen and its substrates in lysosomes. Lysosomes in these tissues usually does not rupture.

• GSD type 2 follows an autosomal recessive pattern.^[5]
• GAA gene mutation responsible for lysosomal enzyme acid α-glucosidase (GAA) deficiency in GSD type 2 and is located on chromosome locus 17q25.^[6][7][5][8]

Conditions associated with glycogen storage disease type 2 include:^[9]

• Cardiomegaly
• Hepatomegaly
• Cardiomyopathy

• On gross pathology, characteristic findings of glycogen storage disease type 2 include cardiomegaly and myopathy.^[10]

• On microscopic histopathological analysis, characteristic findings of glycogen storage disease type 2 include:^[9]
  • Muscle has PAS-positive (diastase sensitive) vacuoles

• On electron microscopic evaluation of skeletal muscle damage as classic infantile GSD type 2 progress include:^[11]

Stage	Microscopic findings
Stage 1	Small glycogen-filled lysosomes in between intact myofibrils
Stage 2	Increase in cytoplasmic glycogen and the size and number of lysosomes combined with fragmentation of myofibrils
Stage 3	Glycogen-filled lysosomes are tightly packed Some show membrane rupture Only few myofibril fragments remain
Stages 4	Most glycogen is cytoplasmic The contractile elements of muscle cells are completely lost
Stage 5	The cells bloat due to the influx of water as glycogen is diluted.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Anmol Pitliya, M.B.B.S. M.D.[2]

Glycogen storage disease type 2 is an autosomal recessive disorder. Glycogen storage disease type 2 is caused by the deficiency of the lysosomal acid alpha-1,4-glucosidase enzyme. GAA gene responsible for the lysosomal acid alpha-1,4-glucosidase enzyme deficiency is located on chromosome 17q25.

• Glycogen storage disease type 2 is an autosomal recessive disorder.^[1]
• Glycogen storage disease type 2 is caused by the deficiency of the lysosomal acid alpha-1,4-glucosidase enzyme. GAA gene responsible for the lysosomal acid alpha-1,4-glucosidase enzyme deficiency is located on chromosome17q25.^[1][2][3][4]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Anmol Pitliya, M.B.B.S. M.D.[2]

Infantile onset glycogen storage disease type 2 (GSD type 2) must be differentiated from other diseases on the basis of characteristics including hypotonia, myopathy, dyspnea, feeding diffculties, absent reflex, macroglossia, hepatomegaly, heart failure, elevated CK, and cardiomegaly. Infantile onset glycogen storage disease should be differentiated from glycogen storage disease type 3, glycogen storage disease type 4, acute Werdnig-Hoffman disease (spinal muscular atrophy), hypothyroidism, endocardial fibroelastosis, myocarditis, congenital muscular dystrophy, mitochondrial/respiratory chain disorder, peroxisomal disorders. Late onset glycogen storage disease type 2 (GSD type 2) must be differentiated from other diseases on the basis of characteristics including hypotonia, muscle weakness, respiratory imapirement, difficulty in walking, hepatomegaly, elevated CK, and cardiomyopathy. Late onset glycogen storage disease should be differentiated from glycogen storage disease type 3, glycogen storage disease type 4, limb girdle muscle atrophy (LGMD), Becker muscular dystrophy (BMD), scapuloperonral syndromes, mitochondrial myopathies, myasthenia gravis, spinal muscular atrophy, polymyositis.

• Infantile onset glycogen storage disease type 2 (GSD type 2) must be differentiated from other diseases on the basis of characteristics including hypotonia, myopathy, dyspnea, feeding diffculties, absent reflex, macroglossia, hepatomegaly, heart failure, elevated CK, and cardiomegaly. Infantile onset glycogen storage disease should be differentiated from glycogen storage disease type 3, glycogen storage disease type 4, acute Werdnig-Hoffman disease (spinal muscular atrophy), hypothyroidism, endocardial fibroelastosis, myocarditis, congenital muscular dystrophy, mitochondrial/respiratory chain disorder, peroxisomal disorders.
• Late onset glycogen storage disease type 2 (GSD type 2) must be differentiated from other diseases on the basis of characteristics including hypotonia, muscle weakness, respiratory imapirement, difficulty in walking, hepatomegaly, elevated CK, and cardiomyopathy. Late onset glycogen storage disease should be differentiated from glycogen storage disease type 3, glycogen storage disease type 4, limb girdle muscle atrophy (LGMD), Becker muscular dystrophy (BMD), scapuloperonral syndromes, mitochondrial myopathies, myasthenia gravis, spinal muscular atrophy, polymyositis.

Diseases	History and Symptoms				Physical Examination				Laboratory Findings	Imaging findings
	Hypotonia	Myopathy	Dyspnea	Feeding difficulties	Absent reflex	Macroglossia	Hepatomegaly	Heart failure	Elevated CK	Cardiomegaly
Glycogen storage disease type II	+	+	+	+	+	+	+	+	+	+
Glycogen storage disease type III	–	+	–	–	–	–	+	–	+	+
Glycogen storage disease type IV	–	+	–	–	–	–	+	–	+	+
Acute Werdnig-Hoffmann disease (spinal muscular atrophy)	+	+	–	–	+	–	–	–	–	–
Hypothyroidism	+	–	–	–	–	+	–	–	–	–
Endocardial fibroelastosis	–	–	+	+	–	–	–	+	–	+
Myocarditis	–	–	–	–	–	–	–	–	–	+
Congenital muscular dystrophy	++	+	–	–	–	–	–	–	–	–
Mitochondrial/respiratory chain disorder	–	+	–	–	–	–	+	–	+	+
Peroxisomal disorders	+	–	–	–	–	–	+	–	–	–

Diseases	History and Symptoms				Physical Examination	Laboratory Findings	Imaging findings
	Hypotonia	Muscle weakness	Respiratory impairement	Difficulty in walking	Hepatomegaly	Elevated CK	Cardiomyopathy
Glycogen storage disease type II	+	Progressive muscle weakness	+	+	+	+	+
Glycogen storage disease type III	+	Progressive muscle weakness	–	–	+	+	+/-
Glycogen storage disease type IV	+	Progressive muscle weakness	–	–	+	+	+/-
Limb girdle muscular atrophy (LMGD)	–	Progressive muscle weakness in pelvis, legs, and shoulders	–	–	–	–	–
Becker muscular dystrophy (BMD)	–	Progressive proximal muscle weakness	+	+	–	+	–
Scapuloperoneal syndromes	–	Progressive muscle weakness behind the knee and around the shoulder blades	–	–	+	+	+
Mitochondrial myopathies	+	Muscle weakness	–	–	+	+	+
Myasthenia gravis	–	Generalized muscle weakness	–	–	–	–	–
Spinal muscular atrophy	–	Asymmetrical muscle weakness, atrophy of voluntary muscles	–	–	–	–	–
Polymyositis	–	Unexplained muscle weakness	–	–	–	–	–

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Anmol Pitliya, M.B.B.S. M.D.[2]

The incidence of glycogen storage disease type 2 (GSD type 2) is approximately 2.5 per 100,000 individuals. Patients of all age groups may develop glycogen storage disease type 2. However, glycogen storage disease type 2 most commonly affects individuals younger than 1 year of age. Glycogen storage disease type 2 usually affects individuals of the Caucasian race.

• The incidence of glycogen storage disease type 2 (GSD type 2) is approximately 2.5 per 100,000 individuals.^[1]
• The incidence of glycogen storage disease type 2 (GSD type 2) is approximately 11.5 per 100,000 individuals in the state of Illinois, United States.^[2]
• The predicted incidence of glycogen storage disease type 2 is approximately 2.5 per 100,000 individuals in Netherlands. This incidence in divided into 0.7 per 100,000 individuals for infantile GSD type 2 and 1.8 per 100,000 individuals for adult GSD type 2.^[3]

• Patients of all age groups may develop glycogen storage disease type 2.^[4]
• However, glycogen storage disease type 2 most commonly affects individuals younger than 1 year of age.^[5]

• Glycogen storage disease type 2 usually affects individuals of the Caucasian race.^[5]

• Glycogen storage disease type 2 affects men and women equally.^[5]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Anmol Pitliya, M.B.B.S. M.D.[2]

The most potent risk factor in the development of glycogen storage disease type 2 is a sibling with glycogen storage disease type 2.

The most potent risk factor in the development of glycogen storage disease type 2 is a sibling with glycogen storage disease type 2.^[1]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Anmol Pitliya, M.B.B.S. M.D.[2]

According to the Recommended Uniform Screening Panel for newborn screening, screening for glycogen storage disease type 2 by Liquid Chromatography-Tandem Mass Spectrometry assay of leukocyte acid α-glucosidase is recommended for newborn.

• Glycogen storage disease type 2 (GSD type 2) is the first lysosomal storage disease to be added to Recommended Uniform Screening Panel for newborn screening panel.^[1][2][3]
• Newborn screening for GSD type 2 by Liquid Chromatography-Tandem Mass Spectrometry assay of leukocyte acid α-glucosidase (GAA) is recommended.
• Low residual GAA activity in leukocytes is determined by this assay.
• Measurement of GAA in blood samples can partially differentiate between infantile onset GSD type 2, late-onset GSD type 2, and pseudodeficiency.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Anmol Pitliya, M.B.B.S. M.D.[2]

The symptoms of classic infantile glycogen storage disease type 2 (GSD type 2) usually develop in the first two months of life and start with symptoms of feeding difficulties and failure to thrive. If left untreated, patients with classic infantile GSD type 2 progress to cardiac failure resulting in death within first two years of life. Most common cause of mortality in late onset glycogen storage disease type 2 is respiratory failure followed by ruptured cerebral aneurysm. Common complications of glycogen storage disease type 2 include cardiomegaly, cardiomyopathy, respiratory failure, respiratory infections, and cerebral aneurysm. Depending on the age of onset of glycogen storage disease type 2, the prognosis may vary. The prognosis is comparatively better as age of onset increases. The presence of classic infantile GSD type 2 is associated with an extremely poor prognosis and the majority of the patients are on ventilator support by a median age of 5.9 months with a median age of death at 8.7 months. Childhood/juvenile GSD type 2 have a relatively good prognosis. Patients may survive up to the third decade of life.

• The symptoms of classic infantile glycogen storage disease type 2 (GSD type 2) usually develop in the first two months of life and start with symptoms of feeding difficulties and failure to thrive.^[1][2]
• Classic infantile GSD type 2 is usually diagnosed at a median age of 4.7 months.
• If left untreated, patients with classic infantile GSD type 2 progress to cardiac failure resulting in death within first two years of life.
• Non-classic infantile GSD type 2 is a less severe form and patients may survive beyond 2 years.^[3]
• Most common cause of mortality in late onset glycogen storage disease type 2 is respiratory failure followed by ruptured cerebral aneurysm.^[4]

• Common complications of glycogen storage disease type 2 include:^[5][4]
  • Cardiomegaly
  • Cardiomyopathy
  • Respiratory failure
  • Respiratory infections
  • Cerebral aneurysm

• Depending on the age of onset of glycogen storage disease type 2, the prognosis may vary. The prognosis is comparatively better as age of onset increases.^[4]
• The presence of classic infantile GSD type 2 is associated with an extremely poor prognosis and the majority of the patients are on ventilator support by a median age of 5.9 months.^[1]
• The median age of death is 8.7 months.
• Classic infantile GSD type 2 patients with supportive and palliative treatment also have a very poor prognosis with mortality before 12 months of age.
• Prognosis of non-classic infantile GSD type 2 is also poor but some patients may survive beyond 2 years.^[3]
• Childhood/juvenile GSD type 2 have a relatively good prognosis. Patients may survive up to the third decade of life.

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