December 2011
33
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The natural course of renal function in GSDI shows a biphasic pattern (with a peak GFR in the
midsecond decade) of hyperfiltration, later accompanied by microalbuminuria and overt
proteïnuria, followed by a decline in GFR thereafter. Optimal metabolic control has a
renoprotective effect on the development of microalbuminuria and a possible renoprotective
effect on the development of proteïnuria in GSD 1 patiënts. A significant decrease in GFR was
observed after starting ACE inhibitors. As proteïnuria and hypertension develops this may
deteriorate the renal function leading to end-stage renal disease. Haemodialysis, continuous
ambulatory peritoneal dialysis and renal transplantation are therapeutic options for end-stage
renal disease. Regular analysis of blood, urine and renal function is obligatory.
1,4,6
Haematological disorders
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Anaemia in GSD 1 patiënt can arise from iron, folic acid or vitamin B12 deficiency or from
hepcidin production by a liver adenoma. After determination of the cause appropriate treatment
can be started.
1
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Coagulation disorders results from impaired platelet function (both aggregation and adhesion),
causing epistaxis, easy bruising and menorrhagia. The prolonged bleeding time can be corrected by
continuous glucose intake (either orally or intravenous). Use of DDAVP has also been reported to
reduce bleeding complications.
2
Gynaecological issues
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Polycystic ovaries (PCO) is a common ultrasound finding in adolescent and adult female patiënts.
However the other clinical features of polycystic ovary syndrome are generally not seen. Their
effect on reproductive function is unclear, although it might affect ovulation and fertility in some
women with GSD.
2
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Menorrhagia and increased vaginal spotting has been known to occur due to the bleeding
abnormalities.
2,3
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Several successful pregnancies have been reported in patiënts with GSD 1, although specific risks
are present. These include the occurrence of hypoglycaemia, possible increase in size and number
of adenomas, or a further decrease in renal function and biochemical fluxes (hyperlipidemia,
hyperuricemia). Because of the increase in carbohydrate requirements early in the pregnancy and
the risks associated with hypoglycaemia regular blood glucose measurements are recommended.
Besides this frequent follow-up evaluation of the biochemical targets is warranted and monitoring
of lactate may also be beneficial in an attempt to maximize metabolic control. It is generally
advised to cease treatment with ACE-inhibitors preconceptionally. A transient worsening of renal
function during pregnancy is possibly caused by hemodynamic changes in pregnancy and the
discontinuation of ACE-inhibitors. AT II-antagonists might serve as an alternative in this case.
Metabolic deterioration during delivery can be a serious risk for the mother and child. Therefore
frequent glucose controls and adequate treatment with glucose infusion are recommended during
delivery.
7
Cardiovascular complications
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Hyperlipedemia can be severe, although atherosclerosis and cardiovascular morbidity and
mortality is infrequent. Skin xanthomas over the extremities and retinal changes can be found.
Furthermore hypertriglyceridemia can increase the risk of pancreatitis.
1,2,5
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Hypertension can arise as result of renal failure. Blood pressure should be measured at each
outpatiënt visit. If ACE-inhibitors are insufficient effective in lowering the blood pressure additional
blood pressure lowering medication should be started.
3,5
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Pulmonary hypertension, which subsequently leads to progressive heart failure, may develop in
the second decade or later. The etiology of pulmonary hypertension is not known. After the first
decade monitoring by ECG and cardiac ultrasonography is recommended.
1,2
Bones and joints
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Osteopenia is a known complication in GSD 1 patiënts. It is most likely caused by both decreased
bone matrix formation and decreased bone mineralisation. This results in an increased risk of bone