Glycogen storage diseases

1. Liver Glycogen Storage Diseases
Clinical and Management Updates
Metabolic Liver Disease
Jan 13-14, 2012
Priya S Kishnani, MD
Division Chief, Medical Genetics
Duke University Medical Center

2. The glycogen storage diseases (GSDs)
• Genetic deficiencies that result in the storage of
abnormal amounts and/or forms of glycogen
• Some deficiencies affect only one tissue, others
several, and even individuals with the same disease
class can have heterogeneous manifestations.
• Focus today: Liver GSDs

3. Eat: Store energy
Fast: Release stored energy
Energy = glucose

4. Glycogen Storage Diseases

5. Brain Fuel Utilization
Fasting fuel system
Glycogenolysis Gluconeogenesis
1 Hour
Meal
4 Hours
Ketogenesis
10-12 Hours

6. Portion of a glycogen molecule

7. Structure and degradation of
Glycogen

8. GSD TYPE
Deficient Enzyme
Tissue Involved
Clinical Findings
GSD 0
Glycogen Synthase
Liver
Hypoglycemia,
ketosis
GSD Ia
Glucose-6phosphatase
Liver, Kidney
Hypoglycemia,
hepatomegaly, lactic
acidosis,
hyperlipidemia
GSD Ib
Glucose-6phosphatase
translocase
Liver, Kidney
GSD Ia plus
neutropenia and
infections
GSD II
Acid alphaglucosidase
(lysosomal)
Cardiomyopathy,
myopathy
Infants:
cardiorespiratory
failure
Later onset:
myopathy
GSD IIIa
Debranching
enzyme
Liver, muscle, heart
Hypoglycemia,
hepatomegaly,
myopathy
GSD IIIb
Debranching
enzyme
Liver
Hypoglycemia,
hepatomegaly

9. GSD TYPE
Deficient Enzyme
Tissue Involved
Clinical Findings
GSD IV
Branching Enzyme
Liver
Hypoglycemia,
hepatomegaly
GSD V
Phosphorylase
Muscle
Exercise
intolerance,
myoglobinuria
GSD VI
Phosphorylase
Liver
Hepatomegaly
GSD VII
Phosphofructokinase
Phosphoglycerate
kinase
Phosphoglycerate
mutase
Muscle
Exercise intolerance
GSD IX
Phosphorylase b
kinase
Liver
Hepatomegaly

10. Glycogen Storage Disease
The Liver GSDs
GSD Ia
GSD Ib
GSD III
GSD IV
GSD VI
GSD IX (subtypes)
GSD XI(Fanconi-Bickel
syndrome)
GSD 0
Liver

11. Glycogen Storage Disease type I
Von Gierke Disease
• Inherited autosomal recessive disease
• Estimated incidence is 1:150,000 births
• Often picked up due to hypoglycemia or
hepatomegaly
• GSD Ia – glucose-6-phosphatase deficiency
• GSD Ib – lack of transporter protein for glucose-6phosphatase
• Genes known to be associated with GSDI are G6PC
(GSDIa)- accounts for ~ 80% of GSDI cases, SLC37A4
(GSDIb)- accounts for ~ 20% of GSDI cases

12. Metabolic sequele of GSD I
GSD-I

13. GSD I - Childhood
• Enlarged liver and kidneys (due to glycogen
and lipid storage)
• Retarded growth
• Low blood sugar
• High blood lactate, lipid and uric acid

14. 5 yr boy with
GSD-Ia
hepatomegaly
hepatomegaly

15. Goals of nutritional therapy for GSD
Type I
• Prevent hypoglycemia
• Correct metabolic derangements
• Provide optimal nutrition to support
growth and development

16. Treatment Strategy:
Maintain Normoglycemia
• Methods
– Frequent feeding
– Continuous glucose infusion
• Total parenteral nutrition
• Intragastric feeding
– Uncooked cornstarch
• 1.75-2.5 g/kg q 6 hours

17. Diet Guidelines for GSD I
Nutrition Composition
• Carbohydrates (60-70%)
– Complex sources – starches
– No sucrose or fructose
– Limit lactose/galactose (1 serving dairy/day)
– Cornstarch
• Protein (10-15%)
– High biological value
– Lean sources

18. Night time tube feeding
GSD Type I
• Formula – Sucrose, fructose, lactose free
• Primarily to provide glucose
– Infant:
8-10 mg glucose/kg/min
– Young child:
8 mg glucose/kg/min
– Older child:
6 mg glucose/kg/min
– Adult:
4-5 mg glucose/kg/min
• Alarm in case of failure
• Eat or take CS within 30 minutes of
discontinuing tube feeding

19. Long-term Complications of GSD-I
• growth failure
• gout
• osteoporosis
• anemia
• renal calcification
• pulmonary hypertension
• renal dysfunction
• Pancreatitis
• hepatic tumours
• Diabetes Mellitus, type II
– Adenoma, HCC
• hyperlipidemia
• polycystic ovaries
• (inflammatory bowel disease)
• (bacterial sepsis)

20. GSD I - Hepatic Adenomas
• Some follow-up studies suggest prevalence of about
50%, similar to that described in past
• Retrospective data (European registry) shows ~50%
prevalence in patients >age 20
• Other reports suggest lower incidence, and even regression, of
adenomas in adequately treated patients
• Complications of HCA include
– bleeding
– malignant transformation, poor prognosis with HCC
• Metastasis to lung and bone
• GI bleeds and liver failure most common causes of death

22. Medical Management of GSD I
• Allopurinol for gout
• Lipid lowering medications
• Citrate supplementation for low citrate (prevent
kidney stones)
• ACE inhibitor for microalbuminuria
• Kidney transplantation for kidney failure
• Liver transplantation if other medical interventions
fail (adenomas)
• GCSF for Type lb

23. GSD I diagnosis:
• Mutation analysis: For GSD Ia there are ~80 disease
causing mutations known in the G6PC gene, some
mutations are specific for different ethnic group (90%
pick up).
• For GSD Ib there are ~70 disease causing mutations
reported in G6PT gene so far. Mutations in exon 8 are
more prevalent (60% pick up)
• Mutational diagnosis is useful for prenatal and carrier
testing.
• Enzyme analysis on liver biopsy, proving actual
enzyme deficiency is the final genetic test.

24. Hypovitaminosis D in GSD type I
• 16 of 26 (61.5 %) GSD I patients had 25-hydroxy
vitamin D levels <30 ng/ml despite supplementation.
• Restrictive diet, metabolic derangements and
intestinal malabsorption possible reasons for
hypovitaminosis D
• Suggest 25(OH)D considered in routine evaluation of
GSD I
Banugaria SG, Austin SL, Boney A, Weber TJ, Kishnani PS. Hypovitaminosis D
in glycogen storage disease type I. Mol Genet Metab. 2010 Apr;99(4):434-7.

25. Use of Medium Chain Triglycerides in
GSD I
• 2 patients with GSD Ia and one with GSD Ib treated with
classical GSD diet and supplemented with MCT fats.
• Improved metabolic control: MCT diet led to decreased uric
acid levels in all three and decreased triglycerides in youngest
patient.
• MCT diet reduced calories needed to maintain blood glucose
and led to improved growth
Das AM, et al. GSD type 1: impact of MCTs on metabolic control and growth. Ann Nutr
Metab. 2010;56(3):225-32
• 13 year old and two infants with GSD Ia received MCT milk
• Lactate levels and triglyceride levels decreased in the 3
patients
Nagasaka H, et al. Improvements of hypertriglyceridemia and hyperlacticemia in
Japanese children with GSD type 1a by MCT milk. Eur J Pediatr. 2007
Oct;166(10):1009-16

26. GSD III (Debranching enzyme
deficiency)

27. Debrancher enzyme

29. GSD-III subtypes:
a: Debrancher activity deficient in liver and
muscle (85% of cases)
b: Debrancher activity deficient only in liver
(15% of cases)

30. Glycogen Storage Disease Type III
(GSD – III) Clinical Variability
•
•
•
•
•
Hepatomegaly
Growth retardation
Hypoglycemia
Hyperlipidemia
Elevated liver
transaminases
• Myopathy
±
• Cardiomyopathy

31. Major phenotypic expression: GSD-III
• Hypoglycemia- improves with age
• Massive hepatomegaly- due to abnormal
glycogen accumulation
• Progressive cirrhosis can occur
• Skeletal myopathy in Type IIIa
• Hyperlipidemia
• Hepatic adenomas not Lack of :
Lactic acidemia
as common as GSD I
Hyperuricemia
glucagon response
• Elevation of AST and ALT And a normalcarbohydrate meal two
hours after a
distinguishes GSD-III from GSD-I

32. Complications associated with GSD III
Highly Variable
• Clinical signs: hepatomegaly short stature, +/skeletal myopathy, cardiomyopathy
• Liver cirrhosis in some, HCC also noted in long
term survivors
• Biochemical Consequences: hypoglycemia
(improves with age), hyperlipidemia, elevated
liver enzymes (transaminases)

33. Type III-GSD deficiency

35. Adult patient with GSD IIIa

36. • The neuromuscular manifestations of GSD III are not
well characterized.
• Medical records of 40 patients seen at Duke
University during 1990-2009 were reviewed.
• The neuromuscular manifestations of GSD III include
myopathy and neuropathy and are more likely to
occur with increasing age
• Intrinsic hand muscle weakness is likely due to a
combination of nerve and muscle dysfunction
• Implications for treatment

38. Treatment of GSD III
• Less demanding than in Type I
• Frequent meals high in carbohydrates and
cornstarch as well as high protein diet.
• Physical therapy for the progressive myopathy
• Liver transplant if end stage cirrhosis

39. GSD type III diagnosis:
• Large gene with 35 exons
•For GSD III b (no muscle disease) mutational analysis is
done for two common mutations (picks up 90% of mutant
alleles)
• GSD III linkage analysis offered only to families with
known family history of GSD III and where intra-genic
markers are informative
• Liver and or muscle biopsy- Enzymatic analysis of DE deficiency
- Glycogen content and structure

40. GSD IV

42. Portion of a glycogen molecule
Lack of branching makes glycogen insoluble, glycogen
appears like fibers of amylopectin, bad for the liver

43. GSD IV (Amylopectinosis) common
clinical presentation:
Extremely heterogeneous in terms of tissue
involvement, age of onset and clinical manifestations
•
• Hepato-splenomegaly due to accumulation of
amylopectin-like structures in affected tissues
• Elevated liver enzymes (transaminases)

44. GSD IV presentation variability:
• Progressive liver cirrhosis, failure to thrive
• Non-progressive milder hepatic form
• Multisystem disease including cardiac and skeletal
muscle, nerve and liver (normal BE activity)
• Fatal neonatal neuromuscular form
(cardiomyopathy, arthrogryposis, even hydrops fetalis)
•Adult polyglycosan disease

45. Treatment of GSD-IV
• NONE
Supportive dietary measures
Liver transplant ---but some patients MAY
show no progression so wait and see, before
referral to surgeons

46. GSD IV diagnosis:
•
DNA sequencing of the GBE gene
• Muscle, skin fibroblasts or liver biopsy to
determine BE enzymatic deficiency and/or
histology are the norms

47. GSD VI (Hers)
• Liver specific phosphorylase deficiency
• Typically benign course, mild hypoglycemia,
hepatomegaly and growth retardation
• Severe forms with significant ketosis being
recognized
• Treatment- avoid fasting, cornstarch for
hypoglycemia

49. GSD VI lab diagnosis:
•Liver biopsy measures the deficient
phosphorylase enzyme activity and also measures
elevated glycogen content (rare, benign).
•Mutation analysis available

50. GSD IX
• Accounts for about 25% of all GSDs
• Caused by deficiency of glycogen phosphorylase
kinase (PhK)
–
–
–
–
Activates glycogen phosphorylase
Key regulatory enzyme in glycogen metabolism
Complex, multi-subunit enzyme
4 copies each of 4 different subunits, each with tissuespecific expression/isoforms

51. Subunit
Gene(s) Chromosome
location
Tissue
Mutations found in
expression GSD IX?
alpha
(regulatory)
PHKA1
Xq12-q13
Muscle
PHKA2
Xp22.2.p22.1
Liver
beta
(regulatory)
PHKB
16q12-q13
Liver &
muscle
Yes – autosomal
recessive GSD IX
(mild)
gamma
(catalytic)
PHKG1
PHKG2
7p11.2
Muscle
16p12.1-p11.2 Liver
No
Yes – autosomal
recessive GSD IX;
can be severe
delta
CALM1
(calmodulin, CALM2
regulatory)
CALM3
Yes – rare, muscle
form of GSD IX
Yes - most common
form of GSD IX (75%
of cases)
14q24-q31
Ubiquitous No
2p21
Ubiquitous No
19q13.2-q13.3 Ubiquitous No

52. GSD IX
•
•
•
•
•
Features often similar to GSD III
Elevations of AST and ALT
Patients can have a significant ketosis
CPK rarely elevated
Enzymology /mutation analysis often needed
to confirm diagnosis

53. GSD IX
• Treatment is symptomatic
– If hypoglycemia present, treat accordingly
– Improved growth with increased complex
carbohydrates presumably by reducing demand
for gluconeogenesis
– Increased protein may also be beneficial
(alternative source of energy)

54. (GSD XI)
Fanconi-Bickel syndrome
• Presentation in infancy typically from 3-10 months
with failure to thrive, hepatorenomegaly, proximal
renal tubular dysfunction, and rickets.
• At early stage, patients may also present with fever,
vomiting, and diarrhea
• Hepatomegaly- Liver size typically normal at birth
and increases in infancy; Hepatomegaly typically
recedes after puberty.
• Liver biopsy- glycogen accumulation present

55. Fanconi-Bickel syndrome (GSD XI)
• Fasting hypoglycemia; postprandial
hyperglycemia also observed
• Some patients diagnosed with diabetes
mellitus and treated with insulin
• Later stage clinical features: growth
delay, moon-shaped face, fat deposition in
shoulders and abdomen, delayed dentition
and delayed puberty, increased fracture
risk, and pancreatitis

56. (GSD XI) Fanconi-Bickel syndrome
• Autosomal recessive; caused by mutations in GLUT2
gene (SLC2A2)
• GLUT2, glucose-transporter-2, a monosaccharide
transporter
• GLUT2- mediates transport of D-glucose, to lesser
extent mediates transport of D-galactose, Dmannose, and D-fructose
• Expressed in hepatocytes, pancreatic beta-cells, and
basolateral membrances of intestinal and renal
epithelial cells
• Clinical molecular testing available
• Clear genotype/phenotype correlation not reported

57. Fanconi-Bickel syndrome
Clinical management
• Avoid fasting hypoglycemia with small, frequent
meals, and uncooked cornstarch overnight;
• Can follow ketogenic diet
• Improved growth and decreased liver size observed
in patients in good metabolic control
• For treatment of effects of renal tubulopathysupplement electrolytes and water
• Supplement vitamin D and phosphate for
hypophosphatemic rickets

58. Conclusions
•
•
•
•
Several liver GSDs (GSD I, III, IV, VI, IX, XI)
Based on features can differentiate largely
Molecular diagnosis now available
Liver biopsy for enzyme testing in most cases
useful
• Liver GSDs fairly common in Indian population
• Treatment simple ( cornstarch, diet, and
replacement of missing elements)
• Can be life threatening if not diagnosed early

59. GSD I - Pregnancy

60. Modified Cornstarch Therapy
First trials with Glycosade in Europe were encouraging
• short-term double-blind cross-over pilot study
comparing uncooked physically modified cornstarch
(WMHM20) with uncooked cornstarch in patients
• 21 patients with GSD types Ia, Ib and III; ages 3-47, 9
female
Bhattacharya K, et al. A novel starch for the treatment of glycogen storage disease. J Inherit
Metab Dis (2007)30:350-357

61. Modified Cornstarch Therapy
• Median starch load duration
9 hours for WMHM20 and 7
hours for uncooked
cornstarch
• Glucose decreased more
slowly and lactate
suppressed faster for
WMHM20
Bhattacharya K, et al. A novel starch for the treatment
of glycogen storage disease. J Inherit Metab Dis
(2007)30:350-357

62. Modified Cornstarch Therapy
– Glycosade maintained
BG longer than Argo
– Argo demonstrated a
higher peak glucose
concentration and a
more rapid rate of fall
Correia, et al. Use of modified
cornstarch therapy to extend
fasting in glycogen storage
disease types Ia and Ib. Am J Clin
Nutr (2008) 88:1272-6

63. Acknowledgements
• Our patients and their families
• Treating physicians and other health care
personnel world wide
• Collaborations with Dr Nagral at Jaslok
• NIH, NCRR
• AGSD

64. Acknowledgements
• Duke University
•
•
•
•
•
•
•
•
Anne Boney
Jennifer Sullivan
Deeksha Bali
Dwight Koeberl
Don Frush
Luis Franco
Vidya Krishnamurthy
YT Chen
• Boston Children’s
– David Weinstein
• Nemours Children
Hospital
– Pamela Arn
• Indian Team
–
–
–
–
Madhulika Kabra
Sheela Nampoothri
Sujatha Jagadeesh
Aabha Nagral

67. Glycogen Storage Disease III
• Inherited Autosomal Recessive
• Cori’s Disease
• Amylo-1,6-glucosidase (debrancher)
deficiency, AGL is associated gene
– Glycogen breakdown is incomplete (abnormal
glycogen w/ short outer chains accumulates)
• Gluconeogenesis intact
• GSD IIIa - Liver and Muscle (75-85%)
• GSD IIIb - Liver only (15-25%)

68. GSD IIIa
• GSD IIIa (liver and muscle) can mimic GSD I in
infancy/young child
– May present with hepatomegaly and
hypoglycemia (with ketosis)
• May have hyperlipidemia, but uric acid and lactic acid
normal
• Confirmed by absence of enzyme activity in liver and
muscle in cultured fibroblasts.

69. GSD IIIa - Treatment
• Infancy/Young child – may mimic GSD I
– Avoid fasting; frequent feedings to prevent hypoglycemia
(standard formula)
– Small frequent meals with complex carbs and increased
protein
• alternative source of energy and to prevent muscle protein
turnover)
• Milk, protein powder (can be mixed with cornstarch)
– Low sugar, but NO “diet restrictions”
– May require cornstarch and/or night time tube feeding
• CS dose may be same as GSD I or can be less
• Rates of TF may be same as GSD I or can be less

70. GSD IIIa – Diet Treatment
• High protein; complex carbs, low sugar
• Dr. Slonim: 25 – 30% pro; 35 – 40% cho; 30 – 35% fat
• 25% pro; 45% cho; 30% fat
– Goldberg T, Slonim AE. Nutrition therapy for hepatic glycogen
storage diseases. J Am Diet Assoc 1993;93:1423-1430

71. GSD IIIa
• Adult – myopathy ~3rd or 4th decade
– Hypoglycemia improves; myopathy worsens;
cardiomyopathy
– Concern with hepatic cirrhosis and carcinoma
• Demo, E, et al, Glycogen storage disease type IIIhepatocellular carcinoma a long-term complication?
Journal of Hepatology. 2007;46:492-498
– Bone Mineral Density should be monitored

72. GSD IIIb
• GSD IIIb (liver only)
– Infancy: may mimic GSD I; frequent feedings;
avoid fasting/hypoglycemia
– Young child: may need CS and/or night time tube
feeding
– May encourage protein as alternative source of
energy, but not as important as in IIIa
– Adults: require little treatment; monitor during
illness/stress

73. GSD IV
• Anderson’s disease
• Autosomal recessive
• Amylo-1,4-1,6transglucosidase deficiency
– Glycogen Brancher Enzyme
(GBE) deficiency; GBE1 gene
• Accumulation of an
amylopectin-like
polysaccharide

74. GSD IV
• Typically presents with liver disease, progresses to cirrhosis
and death (5 y)
– Liver transplant has been done for those with progressive hepatic
failure
• Also a non-progressive liver presentation
–
McConkie-Rosell A, et al. Clinical and laboratory findings in four patients with the non-progressive
hepatic form of type IV glycogen storage disease. J Inher Metab dis. 1996:19;51-58
• No specific treatment
– If hypoglycemia; treat accordingly
• Frequent feedings; high in complex carbs
– Dietary management of liver failure
– Monitor for hepatic carcinoma

75. GSD VI, IX
• GSD VI – Hepatic Phosphorylase, Hers’ disease
– caused by mutations in PYGL gene
– Autosomal Recessive
• GSD IX – Phosphorylase B kinase
– More common of the 2
Clinically similar
• Short stature (eventually achieve normal height), variable
hepatomegaly, variable hypoglycemia

76. GSD IX – variable inheritance; many
isoforms
• Phosphorylase kinase
deficiency - obstructs
glycogen breakdown
– Usually only partially
deficient; so some
glucose available
– Gluconeogenesis intact
– May not have severe
hypoglycemia

77. GSD IX
• Accounts for about 25% of all GSDs
• Caused by deficiency of glycogen phosphorylase
kinase (PhK)
–
–
–
–
Activates glycogen phosphorylase
Key regulatory enzyme in glycogen metabolism
Complex, multi-subunit enzyme
4 copies each of 4 different subunits, each with tissuespecific expression/isoforms

78. Subunit
Gene(s) Chromosome
location
Tissue
Mutations found in
expression GSD IX?
alpha
(regulatory)
PHKA1
Xq12-q13
Muscle
PHKA2
Xp22.2.p22.1
Liver
beta
(regulatory)
PHKB
16q12-q13
Liver &
muscle
Yes – autosomal
recessive GSD IX
(mild)
gamma
(catalytic)
PHKG1
PHKG2
7p11.2
Muscle
16p12.1-p11.2 Liver
No
Yes – autosomal
recessive GSD IX;
can be severe
delta
CALM1
(calmodulin, CALM2
regulatory)
CALM3
Yes – rare, muscle
form of GSD IX
Yes - most common
form of GSD IX (75%
of cases)
14q24-q31
Ubiquitous No
2p21
Ubiquitous No
19q13.2-q13.3 Ubiquitous No

79. Subtypes of phosphorylase kinase deficient
GSDs (GSD IX)
Inheritance
Tissue affected
Mutant gene
X-Linked recessive
Muscle
Liver (XLG1, detectable on RBCs)
Liver (XLG2, blood cells normal)
PHKA1 (Xq12)
PHKA2 (Xp22)
PHKA2 (Xp22)
(most common)
Autosomal Recessive Liver & Muscle (detectable on RBC), mildest PHKB (16q)
Liver (detectable on RBC), Severe phenotype PHKG2 (16p)
Muscle
PHKG1 (7p12)
Heart
PHKG1 (7p12)
XLG1 patients - Blood and liver PHK deficiency. ~20 disease causing
mutations known in the structural part of the gene PHKA2.
XLG2 patients - PHK activity deficient in Liver but can not be proven in vitro, have
mutations in the regulatory part of same gene PHKA2 ~ 4 mutations known so far.

80. GSD IX
• Treatment is symptomatic
– If hypoglycemia present, treat accordingly
– Improved growth with increased complex
carbohydrates presumably by reducing demand
for gluconeogenesis
– Presumably increased protein may also be
beneficial (alternative source of energy)

81. GSD IX
• For a GSD IX child presenting with hypoglycemia and growth delay…
– Keep Food and Blood Glucose Record (how long can they fast?)
– DIET ORDER: High Protein, High Complex Carbohydrates, Avoid Simple
Sugars, Low Fat
– Prescribe Cornstarch at bedtime if needed
• If needed can use similar diet for GSD VI
Schippers HM, Smit PA, Rake JP, Visser G. Characteristic growth pattern in male X-linked phosphorylase-b kinase
deficiency. J Inherit metab Dis 2003;26:43-47.
Adamenko RS, Brandes B, Karpen SJ: A 5-year-old boy with hepatomegaly and linear growth delay. Current
Opinion in Pediatrics 1998, 10:523-526.
Goldberg T, Slonim AE. Nutrition therapy for hepatic glycogen storage diseases. J Am Diet Assoc 1993;93:14231430.

82. GSD 0
• Glycogen Synthase Deficiency
– Autosomal recessive disease
– Few reported cases, several mutations
– Symptoms include ketotic hypoglycemia with
fasting, no hepatomegaly, and postprandial
hyperglycemia, hyperlactatemia and
hyperlipidemia
– Glycogen Synthase is absent in the liver, but
present in muscle

83. GSD 0
• Treatment – Prevent hypoglycemia
– Small frequent meals with complex carbohydrates
and protein through out the day
– Cornstarch may be used at bed time to prevent
hypoglycemia
Weinstein DA, et al. Hepatic glycogen synthase deficiency: An infrequently recognized cause of ketotic
hypoglycemia. Molecular Genetics and metabolism. 2006;87:284-288.

84. Modified Cornstarch Therapy
First trials with Glycosade in Europe were encouraging
• short-term double-blind cross-over pilot study
comparing uncooked physically modified cornstarch
(WMHM20) with uncooked cornstarch in patients
• 21 patients with GSD types Ia, Ib and III; ages 3-47, 9
female
Bhattacharya K, et al. A novel starch for the treatment of glycogen storage disease. J Inherit
Metab Dis (2007)30:350-357

86. Modified Cornstarch Therapy
• Median starch load duration
9 hours for WMHM20 and 7
hours for uncooked
cornstarch
• Glucose decreased more
slowly and lactate
suppressed faster for
WMHM20
Bhattacharya K, et al. A novel starch for the treatment
of glycogen storage disease. J Inherit Metab Dis
(2007)30:350-357

87. Modified Cornstarch Therapy
• Pilot Study done in the US was also
encouraging:
– Randomized, 2-d, double blinded, crossover pilot
study (12 subjects: 6 with GSD Ia and 6 with GSD
Ib, >13 years)
– Heat-moisture processed cornstarch Glycosade
(Vitaflo) compared to Argo brand CS
Correia, et al. Use of modified cornstarch therapy to extend fasting in glycogen storage
disease types Ia and Ib. Am J Clin Nutr (2008) 88:1272-6
• A Larger Trial is planned in the near future

88. Modified Cornstarch Therapy
– Glycosade maintained
BG longer than Argo
– Argo demonstrated a
higher peak glucose
concentration and a
more rapid rate of fall
Correia, et al. Use of modified
cornstarch therapy to extend
fasting in glycogen storage
disease types Ia and Ib. Am J Clin
Nutr (2008) 88:1272-6