Liver glucose 6-phosphatase deficiency

Fructose-1,6-bisphosphatase deficiency, first describ ed by Baker and Winegrad in 1970, has now been reported in approximately 30 cases. It is more common in women and is inherited as an autosomal recessive disorder. Initial manifestations are not strikingly dissimilar from those of glucose-6-phosphatase deficiency. Neonatal hypoglycemia is a common presenting feature, associated with profound metabolic acidosis, irritability or coma, apneic spells, dyspnea, tachycardia, hypotonia and moderate hepatomegaly. Lactate, alanine, uric acid and ketone bodies are elevated in the blood and urine [11]. The enzyme is deficient in liver, kidney, jejunum and leukocytes. Muscle fructose-1,6-bisphosphatase activity is normal. 

D-2) Glucftse 6-phosphatase deficiency Cl pe I GSD Von Gierke s Disease). There is a deficiency at this step in the formation of glucose by the liver. Glucose 6-phosphate instead forms other things and the flow of reactions shifts to ... 

An infant with an enlarged liver has a glucose 6-phosphatase deficiency. This infant... 

Figure 26.6 GSD I, von Gierke s disease. GSD I (autosomal recessive) is caused by hepatic glucose 6-phosphatase deficiency so the liver loses its ability to prevent hypoglycaemia. Neonatal hypoglycaemia can be severe and glycogen is stored in excess in the liver and kidney. Other features that are a consequence of accumulation of glucose 6-phosphate are hyperlactataemia, hyperlipidaemia, hyperuricaemia and gout.

Gout has been observed occasionally in young patients with glucose-6-phosphatase deficiency and glycogen deposition in liver and kidney. In these cases, the symptoms of gout are unresponsive to therapy, and the patient dies at an early age. Whether the increase in blood lactate levels influences the manifestation of gout is not certain. 

Characteristically the disease is associated with liver gluoose-6-Phosphatase deficiency. However, oases are on record who show typical clinical and biochemical features of G.S.D.I yet, normal glucose-6-phosphatase has been found by in vitro measurements of liver enzyme. 

Type 1 Von Gierke s disease Deficiency of glucose-6-phosphatase Liver cells and renal tubule cells loaded with glycogen. Hypoglycemia, lactic-acidemia, ketosis, hyperlipemia. 

Phosphoenolpyruvate carboxykinase (PEPCK) deficiency is distinctly rare and even more devastating clinically than deficiencies of glucose-6-phosphatase or fructose-1,6-bisphosphatase. PEPCK activity is almost equally distributed between a cytosolic form and a mitochondrial form. These two forms have similar molecular weights but differ by their kinetic and immunochemical properties. The cytosolic activity is responsive to fasting and various hormonal stimuli. Hypoglycemia is severe and intractable in the absence of PEPCK [12]. A young child with cytosolic PEPCK deficiency had severe cerebral atrophy, optic atrophy and fatty infiltration of liver and kidney. 

The most common glycogen storage disease. Type I or von Gierke disease, is a deficiency in glucose 6-phosphatase in which glycogen structures are normal however, the liver is unable to dephosphory-late glucose 6-phosphate, and it remains trapped In the cell. 

The release of glucose from the glycogen stores in the liver is mediated by glucose 6-phosphatase, which is apparently embedded within the membranes of the endoplasmic reticulum. A labile enzyme, it consists of a 357-residue catalytic subrmit,251/252 which may be associated with other subunits that participate in transport.252 253 A deficiency of this enzyme causes the very severe type la glycogen storage disease (see Box 20-D).251 253 Only hepatocytes have significant glucose 6-phosphatase activity. 

Individuals with a glucose-6-phosphatase (G-6-P —> Glucose, in the liver) deficiency develop a glycogen storage disease. This condition results in hypoglycemia, low blood sugar, accumulation of lactic acid and ketones. Distal kidney tubule excretion of uric acid is inhibited and hyperuricemia (XS uric acid) and gout results. 

The glycogen has a normal structure in types 1 and 2 in the former, there is deposition of fat in the liver and kidney, and a decreased activity of glucose-6-phosphatase. The enzyme deficiencies in type 2 are unknown. In types 3 and 4, which are less common, the glycogens have abnormal... 

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