Hypoglycemia deficiency

For many years, there has been concern by medical professionals and nutritionists over the effects of dietary sugar on human health. Sucrose has been imphcated as a cause of juvenile hyperactivity, tooth decay, diabetes meUitus, obesity, atherosclerosis, hypoglycemia, and nutrient deficiencies. 

Glycogenosis type VI (liver myophosphorylase deficiency) gives rise to hepatomegaly and hypoglycemia in childhood. The enzyme involved is under separate genetic control from the muscle isoform and has been assigned to chromosome 14. 

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. 

Type VI Hers disease Deficiency of liver phosphorylase High glycogen content in liver, tendency toward hypoglycemia. 

Increased fatty acid oxidation is a characteristic of starvation and of diabetes meUims, leading to ketone body production by the Ever (ketosis). Ketone bodies are acidic and when produced in excess over long periods, as in diabetes, cause ketoacidosis, which is ultimately fatal. Because gluconeogenesis is dependent upon fatty acid oxidation, any impairment in fatty acid oxidation leads to hypoglycemia. This occurs in various states of carnitine deficiency or deficiency of essential enzymes in fatty acid oxidation, eg, carnitine palmitoyltransferase, or inhibition of fatty acid oxidation by poisons, eg, hypoglycin. 

Camitine deficiency can occur particularly in the newborn—and especially in preterm infants—owing to inadequate biosynthesis or renal leakage. Losses can also occur in hemodialysis. This suggests a vitamin-fike dietary requirement for carnitine in some individuals. Symptoms of deficiency include hypoglycemia, which is a consequence of impaired fatty acid oxidation and hpid accumulation with muscular weakness. Treatment is by oral supplementation with carnitine. 

Inherited defects in the enzymes of (3-oxidation and ketogenesis also lead to nonketotic hypoglycemia, coma, and fatty hver. Defects are known in long- and short-chain 3-hydroxyacyl-CoA dehydrogenase (deficiency of the long-chain enzyme may be a cause of acute fetty liver of pr nancy). 3-Ketoacyl-CoA thiolase and HMG-CoA lyase deficiency also affect the degradation of leucine, a ketogenic amino acid (Chapter 30). 

Because GH deficiency may be accompanied by the loss of other pituitary hormones, hypoglycemia and hypothyroidism also may be noted. 

Hepatic encephalopathy Hyperbilirubinemia Hypocalcemia Hypercalcemia Hyperparathyroidism Hypoparathyroidism Thiamine deficiency (Wernicke s) encephalopathy Diabetic ketoacidosis Nonketotic hyperosmolar coma Phosphate depletion Hypoglycemia Hypoxemia Hypercapnia... 

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. 

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. 

Most patients with pyruvate-carboxylase deficiency present with failure to thrive, developmental delay, recurrent seizures and metabolic acidosis. Lactate, pyruvate, alanine, [3-hydroxybutyrate and acetoacetate concentrations are elevated in blood and urine. Hypoglycemia is not a consistent finding despite the fact that pyruvate carboxylase is the first rate-limiting step in gluconeogenesis. 

In liver phosphorylase deficiency (glycogenosis type VI, Hers disease Fig. 42-1) and in two genetic forms of phosphorylase kinase deficiency, one of which is X-linked recessive, the other of which is autosomal recessive, hypoglycemia is either absent or mild. Symptoms of brain dysfunction do not usually occur (type VIII, Fig. 42-1) [1],... 

Glutaric aciduria type II, which is a defect of P-oxida-tion, may affect muscle exclusively or in conjunction with other tissues. Glutaric aciduria type II, also termed multiple acyl-CoA dehydrogenase deficiency (Fig. 42-2), usually causes respiratory distress, hypoglycemia, hyperammonemia, systemic carnitine deficiency, nonketotic metabolic acidosis in the neonatal period and death within the first week. A few patients with onset in childhood or adult life showed lipid-storage myopathy, with weakness or premature fatigue [4]. Short-chain acyl-CoA deficiency (Fig. 42-2) was described in one woman with proximal limb weakness and exercise intolerance. Muscle biopsy showed marked accumulation of lipid droplets. Although... 

Cushing s disease, hyperparathyroidism, hyperthyroidism, hypothyroidism, hypoglycemia, hyponatremia, hyperkalemia, pheochromocytoma, vitamin B12 or folate deficiencies Neurologic... 

Deficiency of hepatic glucose 6-phosphatase produces a profound fasting hypoglycemia, lactic acidosis, and hepatomegaly. Additional symptoms include ... 

Hypoglycemia Hypoglycemia does not occur in patients receiving metformin alone under usual circumstances, but could occur with deficient caloric intake, strenuous exercise not compensated by caloric supplementation, or during concomitant use with other glucose-lowering agents (such as sulfonylureas) or ethanol. 

The answer is B. While all of the listed conditions are consistent with lethargy and developmental defects, the lactic acidosis rules out pyruvate kinase deficiency. Thiamine and niacin deficiencies are unlikely due to the lack of effect of vitamin supplementation. Excess pyruvate is the source of the elevated alanine in the serum. The clinical findings are thus consistent with pyruvate carboxylase deficiency, which is associated with severe hypoglycemia due to fasting due to impaired gluconeogenesis. 

The answer is C. Pyruvate kinase deficiency is ruled out by the elevated serum lactate levels. The coma is associated with a fasting hypoglycemia, which is indicative of pyruvate carboxylase deficiency. The elevated citrulline and lysine in the serum are due to a reduction of aspartic acid levels, which are caused by the reduced levels of oxaloacetate, the product of the pymvate carboxylase reaction. 

CPT-I deficiency produces a fasting hypoglycemia due to impaired liver function as a consequence of the inability to utilize LCFAs as fuel. 

CPT-II deficiency is more common and mainly manifests as muscle weakness, myoglobinemia, and myoglobinuria upon exercise severe cases lead to hyperketotic hypoglycemia, hyperammonemia, and death. 

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