December 2011
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Glycogen Storage Disease type 3 – 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 3
Glycogen Storage Disease type 3 (GSD 3, MIM 232400) is an autosomal recessive disorder due to
deficiency of the glycogen debranching enzyme (GDE) which leads to excessive amounts of
abnormally structured glycogen in liver and muscle.
1,2
Type IIIa affects both liver and muscle cells
(
approximately 85% of patiënts with GSD 3), whereas type IIIb affects only liver cells
(
approximately 15% of patiënts with GSD 3). GSD 3c and IIId are extremely rare.
1,2
The estimated
prevalence is 1 in 100.000.
3
Accumulation of glycogen with an abnormal structure in liver cells leads to hepatomegaly. The
inability to mobilize liver glycogen may lead to hypoglycaemia and ketosis during (prolonged)
fasting. These features arise predominantly at childhood, next to growth retardation, increased
livertransaminses and hyperlipidemia. During childhood muscle sign are usually limited to minimal
non-progressive hypotonia or mild delay of motor milestones.
1,2
Hypermobility and alignment
disorders can arise due to weakness.
Hepatic features typically improve with age, although progressive liver disease, including liver
fibrosis, cirrhosis, adenomas and carcinoma, can occur.
3
Slow progressive skeletal myopathy
becomes prominent in the third or fourth decade and can give rise to weakness and wasting of
trunk, proximal and distal muscles. Peripheral neuropathy may contribute to this.
3
Hypertrophic cardiomyopathy is detectable in many patiënts with myopathy.
2
In addition
osteoporosis and polycystic ovaries are commonly seen in patiënts with GSD 3.
4
The diagnosis of GSD 3 is based on enzyme studies of liver and muscle tissue or leukocytes in
combination with DNA mutation analysis. Mutations of GSD 3a are found throughout the AGL gene
(
which encodes for GDE), whereas mutations causing GSD 3b are limited to exon 3 of the AGL
gene.
2,3
Treatment
The treatment in patiënts with GSD 3 consists mainly of frequent feeding and in GSD 3a patiënts a
protein rich diet. Continuous nocturnal gastric drip feeding (or late evening meals) can be used in
infancy. Uncooked cornstarch, as a long-lasting source of carbohydrates, can be introduced at the
end of the first year. The use of complex carbohydrates is preferred over simple sugars.
1-4
Blood
glucose (and urine ketosis) should be monitored during illness, with changes in diet, in exercise
routines and at random (to detect asymptomatic hypoglycaemia). Moreover an individual
emergency protocol is obligatory.
4
A small number of medications are used to correct or improve the complications. Beta blockers can
be used in case of hypertrophic cardiomyopathy. Statines can be used to correct hyperlipidemia,
only after optimizing dietary treatment. Both should be used with care since they can respectively
mask hypoglycemia and exacerbate myopathy. Supplementation of calcium and vitamin D can
improve bone mineralisation.
3,4
In case of surgery glucose intake should be assured and coagulation needs to be checked and
corrected. Myopathy might be affected by anaesthesia, therefore non-depolarizing agents and
succinylcholine should be used with care.
4
Complications
Hepatic disorders
During childhood hepatomegaly and elevated liver transaminases predominate. Liver cirrhosis and
(
end stage) liver failure, accompanied by a prolonged protombin time and low albumin, can occur
after regression of the childhood hepatomegaly. Hepatic adenomas are rarely seen in Dutch GSD 3