December 2011
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Glycogen Storage Disease type 1 – Latest Evidence
This part of the document will be changed in the first revision, in which the level of evidence will
be displayed throughout this care pathway.
Glycogen Storage Disease type 1
Glycogen Storage Disease type 1 (GSD 1, MIM 23220) is an autosomal recessive disorder of
carbohydrate metabolism caused by a deficiency of the glucose-6-phosphatase (G6Pase) enzyme
complex. GSD 1 consist of GSD 1a, caused by a deficiency of the catalytic subunit of glucose-6-
phosphatse (G6PC,
EC 3.1.3.9)
, and GSD 1b, caused by a deficiency of the glucose-6-phopsphatase
translocase (G6PT).
1
These deficiencies result in excessive accumulation of glycogen and fat in liver
and kidneys and lead to inadequate hepatic glucose production through normal glucogenolysis and
gluconeogenesis since the final step of these processes are blocked.
1,2
Most patiënts present at 3 or 4 months of age with a protruded abdomen (due to massive
hepatomegaly), truncal obesity, a doll-like face, hypotrophic muscles and growth delay.
2,3
In
addition most patiënts with GSD 1b have intermitted severe neutropenia and neutrophil
dysfunction which predispose to severe infections and to inflammatory bowel disease (IBD).
4
The major biochemical findings are severe fasting hypoglycaemia, lactic acidosis, hyperuricemia
and hyperlipedemia.
2
The overall incidence of GSD 1 is 1 in 100.000 newborns, GSD 1a is four times
as common as GSD 1b.
3
The diagnosis GSD 1 can be based on clinical and biochemical findings
combined with DNA analysis.
1
Treatment
Dietary therapy
to maintain normal glucose concentrations, prevent hypoglycaemia and provide
optimal nutrition for growth and development.
Dietary key elements are:
3,5
-
Frequent daytime feedings: frequent meals and snacks high in complex carbohydrates.
-
Uncooked cornstarch orally: between meals or before bedtime, starting during infancy.
-
Continuous Nocturnal Gastric Drip Feeding through nasogastric or gastrotomy tube.
-
Restriction of galactose and lactose (milk products) and fructose and sucrose (fruit).
-
Restriction of sorbitol en maltitol, other sweeteners can be used
In case of GSD 1b:
4
-
Precaution is needed with the use of uncooked cornstarch since this may exaggerate IBD.
-
Gastrotomy is contraindicated because of the risk of IBD and local infection.
Pharmacotherapy and surgery
can be used to prevent or treat (long term) complications.
Pharmacologic therapy consists of:
3,5
-
Allopurinol is used to prevent gout (and urate nephropathy) in case of hyperuricemia.
-
Citrate supplementation is used to correct lactacidaemia and to prevent urolithiasis and
nephrocalcinosis.
-
Angiotensin converting enzyme (ACE) inhibitor is used to treat microalbuminuria.
-
Other blood pressure lowering medication
(angiotensin II receptor antagonist).i
f blood pressure
remains above p 95 for age, with a p 50 blood pressure as target.
-
Lipid-lowering medication (Firbates or Statines) are used when lipid levels are elevated.
-
Iron in case of iron deficiency anaemia (after excluding other possible causes).
In case of GSD 1b:
1,4
-
Granulocyte colony stimulating factor (G-CSF) is used to prevent recurrent severe infections and
in case of severe IBD. The possible complications (splenomegaly, leukaemia and renal
carcinoma) make stringent follow-up necessary.
-
Immunosuppressive medication (prednisone, 5-ASA) in case of mild IBD.
-
Prophylactic antibiotics (e.g. cotrimoxazol) can be used prevent recurrent infections.