HENA OR MEHANDI APPLIED OVER HEAD OR HANDS MAY CAUSE HAEMOLYSIS.
GET FAMILY MEMBERS FOR GENETIC SCREENING
FEMALES GENERALLY CARRIERS, ASYMPTOMATIC. RARELY THOSE HAVING HIGH PROPORTION OF DEFICIENT CELLS DISPLAY SYMPTOMS
* NAPHTHALENE BALL INGESTION MAY CAUSE SEVERE HAEMOLYSIS
* METABOLIC ACIDOSIS MAY CAUSE HAEMOLYSIS
* VIRAL & BACTERIAL INFECTION MAY TRIGGER HAEMOLYSIS
" Hyperlipidemia
o Patients with GSD type Ia typically have very high serum triglyceride levels with modest elevations of total cholesterol and low-density lipoprotein cholesterol and low levels of high-density lipoprotein cholesterol.
o The etiology of this dyslipidemia is thought to be increased hepatic lipogenesis. However, some evidence also indicates that the cause is decreased triglyceride clearance due to diminished hepatic lipoprotein lipase activity.
o Although this lipid profile is considered atherogenic in the general population, patients with GSD type Ia may not have the same risk. Nevertheless, myocardial infarction at a young age or acute pancreatitis warrants attention.
o Compliance with appropriate dietary therapy is the first line of treatment.
o The recommended diet is comprised of 15-20% fats, equally distributed among saturated and nonsaturated, and daily cholesterol intake of less than 200 mg/d.
o This improves the hypertriglyceridemia in most patients and may decrease the total cholesterol level by 18-25%.
" Persistent hyperlipidemia
o If hyperlipidemia persists despite maximal dietary measures, initiating a trial of drug therapy is reasonable.
o Reports suggest that fibrates and niacin may decrease triglyceride levels by up to 30%, but this effect may not be sustained long-term.
o Additionally, the use of fish oil supplements (eicosapentaenoic acid, 10 g/1.73 m2/d) has been shown to lower triglyceride levels by an average of 49% when used for a 3-month period.
o Statins and bile acid sequestrant resins are probably contraindicated because they may exacerbate the hypertriglyceridemia.
o An obvious need exists for more long-term studies of drug therapy in this setting.
"
" Hepatic adenomas
o Single or multiple hepatic adenomas are observed in up to 80% of patients.
o Although they have been seen in patients as young as 3 years, they usually appear during the second or third decade.
o These adenomas bear a remarkable similarity to pharmacologic estrogen-induced hepatic adenomas, and several hypotheses exist about their development mechanism. Mitochondrial B-oxidation of fatty acids is thought to be inhibited by excess malonyl coenzyme A (due to G-6-phosphatase deficiency), which decreases carnitine palmitoyltransferase I and increases extramitochondrial fatty acid oxidation. This process may be significant in oncogenesis.
o Given the pathophysiologic similarity to estrogen-induced hepatic adenomas, affected patients should use oral contraceptive pills with caution or not at all.
"
" Hepatic adenoma prevention and treatment
o Evidence about using strict dietary control of glucose, lipids, and lactate to prevent adenoma formation and promote regression is conflicting. Reports indicate that many cases may not respond to dietary therapy.
o Monitor hepatic adenomas with biannual or yearly ultrasound examinations. Serum alpha-fetoprotein values should also be measured serially as a potential marker of malignant transformation, which may occur in 11% of adenomas.
o Adenomas may cause symptoms such as pain or vomiting. An acute onset of pain may indicate hemorrhage into the tumor capsule.
o Adenomas that show signs of growth, hemorrhage, necrosis, calcification, or elevated alpha-fetoprotein levels should be referred for definitive diagnosis (ie, via biopsy or resection).
o Once the determination has been made that aggressive therapy is warranted for symptom control, hemorrhage control, or to exclude malignancy, a decision must be made between localized resection or orthotopic liver transplant. A liver transplant has the added benefit of correcting the underlying metabolic defect, but it also means a lifetime of immunosuppression and its associated risks. However, either way, patients require life-long medical therapy.
o Patients must be informed of the potential risks and benefits of each therapy so that they can make the most appropriate decision.
" Renal disease
o Renal disease associated with G-6-phosphatase deficiency was previously thought to manifest mainly as renal enlargement upon ultrasound examination or hematuria from uric acid stones. However, the initial change in affected patients has been shown to be hyperfiltration, which is a nephropathy similar to diabetes.
o This increase in the glomerular filtration rate is not observed at birth, but it is present in up to 50% of patients by age 1 year.
o After several years, progressive proteinuria can be observed that sometimes develops into the nephrotic range. This may be found in up to 70% of patients older than 10 years.
o Along with the proteinuria, a progressive decline in creatinine clearance and the onset of hypertension may occur.
o Eventually, dialysis-dependent renal failure occurs approximately 12 years after the first appearance of proteinuria.
o Most deaths from renal failure occur in older patients who did not receive aggressive dietary management from birth or who did not comply with therapy.
o Although several theories have been suggested, the exact mechanism of the hyperfiltration is unknown.
"
" Renal disease management
o Proper methods to manage associated renal disease are still quite uncertain.
o Probably the most important factor for preventing renal deterioration is patient compliance with a dietary therapy that maintains euglycemia and reduces hyperlipidemia and counterregulatory hormone excess.
o Controlling hyperuricemia helps prevent uric acid stones and uric acid nephropathy.
o If hypertension develops, it should be aggressively controlled to delay the progression of renal damage.
o The main question remains whether angiotensin-converting enzyme inhibitors decrease hyperfiltration and proteinuria and delay the progression or appearance of overt renal failure, as is observed in diabetes.
o A reduction in proteinuria has been observed in a few patients treated on an experimental basis, but no formal trials have been published to answer this question. In the absence of any contraindications, it is probably a reasonable choice in the presence of hypertension.
"
" Hyperuricemia
o Debate exists regarding when to initiate therapy to treat hyperuricemia.
o Most clinicians begin when an affected patient has an episode of acute gouty arthritis, uric acid nephrolithiasis, or gouty tophi. However, initiating therapy in asymptomatic patients who have serum urate levels greater than 420 Β΅mol/L (7 mg/dL) also may be reasonable.
o Treatment usually consists of a dietary review to ensure compliance and 100-300 mg allopurinol daily. Allopurinol should never be started during an acute attack of gout because it may exacerbate the arthritis.
o Any patient with hyperuricemia should maintain appropriate body weight and limit ethanol consumption.
"
" Metabolic bone disease
o Osteopenia and osteoporosis are being increasingly identified in patients with G-6-phosphatase deficiency, but the exact mechanism has not been identified.
o One possible cause is poor dietary calcium intake and increased urinary calcium excretion without a concomitant rise in 25-vitamin D, parathyroid hormone, or skeletal alkaline phosphatase. This represents an inappropriate response to a negative calcium balance.
o Compared to age-matched controls, bone mineral content and bone densitometry may be reduced, even in patients as young as 3 years.
o No clinical trials have been performed on the management of osteoporosis in this population, but it would seem prudent to ensure that the prescribed diet contains adequate calcium and vitamin D. Hopefully, future trials will address the question of antiresorptive therapy such as bisphosphonates.
Surgical Care
" Gastrostomy feeding tube
"
o Placement facilitates overnight, continuous drip feedings.
o Feeding tubes are usually placed shortly after diagnosis, but some clinicians delay placement until age 6-12 months if the diagnosis is made at birth.
o Pay careful attention to ensure a healthy insertion site, and treat any infection early.
" Liver resection and transplantation
"
o Symptomatic hepatic adenomas or possible malignant mass transformation may require resection or liver transplant.
o On occasion, liver transplantation has been advocated when maximal dietary therapy fails to give metabolic control and normal growth. This is controversial because of the life-long risks incurred by immunosuppression.
o Available data indicate that patients with GSD type Ia who received a liver transplant have normal metabolic balance, which allows catch-up growth and improves quality of life.
o Evidence indicates that renal disease (focal segmental glomerulosclerosis) is not prevented or corrected by liver transplantation.