Glucose inborn errors

The twins were referred subsequently to a metabolic specialist because of the suspicion of an inborn error of metabolism. Biochemical testing revealed each had a hyperchloremic (increased blood chloride concentration) metabolic acidosis that was more profound in Elizabeth. Serum levels of glucose and liver transaminases were normal. Urinary organic acids revealed modestly increased concentrations of lactate and ketone bodies. Blood samples and fibroblasts from skin biopsies from both girls were sent to an established diagnostic laboratory for genetic mitochondrial diseases. Tests of respiratory chain complex enzymatic activities were normal. 

In the majority of cases, a UCD can be distinguished from other inborn errors of metabolism by routinely available clinical chemistry tests such as blood gases, acid/base balance, plasma glucose, ammonium, or lactate. Urea production, and hence serum urea nitrogen, is decreased in UCDs. Respiratory alkalosis has few causes and is an important diagnostic clue of hyperammonemia that should trigger measurement of plasma ammonium. 

The greatest advances at the enzyme level have been in understanding the inborn errors associated with lipid metabolism (27). At least nine of these diseases have been described at the enzyme level (Table II). The first five diseases listed in Table II involve enzymes which successively degrade Cer-Glc-Gal-(NeuNAc)-GalNAc-Gal to ceramide, glucose, galactose, and neuraminic acid. No genetic diseases associated... 

Various inborn errors of metabolism (Table 25-1) result from deficiencies or absence of some of the enzymes listed in Figure 25-9. Some of these are discussed later in the chapter. The relationship of carbohydrate metabolism to the production of lactate, ketone bodies, and triglycerides is also depicted in Figure 25-9. The pentose phosphate pathway, also known as the hexose monophosphate shunt, is an alternative pathway for glucose metaboUsm that generates the reduced form of nicotinamide-adenine dinucleotide phosphate (NADPH), which is used in maintaining the integrity of red blood cell membranes, in lipid and steroid biosynthesis, in hydroxylation reactions, and in other anabolic reactions. The complete picture of intermediary metabolism of carbohydrates is rather complex and interwoven with the metabolism of lipids and amino acids. For details, readers should consult a biochemistry textbook. 

TarlovAR, Brewer GJ, Carson PE, et al. 1962. Primaquine sensitivity Glucose-6-phosphate dehydrogenase deficiency An inborn error of metabolism of medical and biological significance. 

Gaucher s disease is an inborn error of sphingolipid metabolism caused by a deficiency of the lysosomal enzyme, acid p-glucosidase (EC 3.2.1.45) which is responsible for cleaving glucosylceramide (GlcCer) into glucose and... 

As the primary site of amino acid, Upid, and glucose metabolism, the liver has a disproportionally high involvanent in inborn errors of metabolisms. 

Some inborn errors of metabolism present with hypoglycemia, occurring after periods of extended fasting. Disorders of reduced tolerance to fasting include glucose homeostasis... 

Overview Sample Handling Glucose Sarcosine, Creatine, and Creatinine Inborn Errors of Metabolism. Polycyclic Aromatic Hydrocarbons Environmental Applications. Sample Handling Comminution of Samples Automated Sample Preparation Robotics. Sampling Theory. 

Chapter 3 Inborn Errors of Metabolism Ceramide Glucose Galactose Galactose N-acetylgalactosamine... 

Cystinuria is the prototype of a number of inborn errors of metabolism believed to result from the deficiency of carrier proteins involved in transporting molecules through the cell membrane. Transport defects in kidney, intestine, or both have also been described for other amino acids— glycine, cystine, tryptophan, methionine—for glucose and galactose, and even for electrolytes such as calcium, chloride, and sodium [173]. Some of these inborn errors are described in other chapters. 

In evaluating food requirements in infancy, one must consider that the infant s enzymic arsenal is not equivalent to that of the adult. We have already mentioned that in guinea pigs and rats, glucose-6-phospha-tase is practically nonexistent until shortly before term, but after term it rises rapidly. In humans, phenylalanine hydroxylase is absent from liver until several weeks after term. If the formation of the enzyme molecules is completely inhibited because of a genetic defect, an inborn error of metabolism develops. In rats, tyrosine transaminase increases immediately after birth and reaches a maximum 12 hours after birth. 

Food contains one polysaccharide (starch) and three disaccharides (maltose, sucrose, and lactose). Salivary and pancreatic amylase digests starch to yield maltose and sucrose, and lactose to yield maltose and sucrose. Sucrose, maltose, and lactose are split by invertase, maltase, and lactase, respectively. The products of the disaccharidase reactions are fructose, glucose, and galactose. Whenever amylase or one of the disacchari-dases is absent from the intestinal content, the undigested sugars pass in the lower part of the intestinal tract and are fermented by the bacterial flora. As a result, lactic acid and volatile acids are formed and stimulate peristalsis and fluid secretion by the intestinal mucosa. Liquid foaming acid and foul-smelling feces are emitted. Amylase may be absent in pancreatic disease. Inborn errors characterized by the absence of intestinal lactase, maltase, and invertase have been described. 

Sucrase (also called saccharase and invertase) hydrolyzes sucrose. In contrast to the abundant information available on the yeast invertase, little is known of the mammalian sucrases. The significance of invertase and lactase in absorption is illustrated by inborn errors of metabolism in which these two enzymes are absent in the intestinal secretion. (The fact that lactase deficiency does not interfere with growth indicates that the galactose needed for biosynthesis of brain lipids or lens proteins can be synthesized endogenously in amounts sufficient to fulfill the metabolic requirements.) In that case, there is an intolerance to lactose or sucrose with no increase in blood glucose levels or without an increase in the levels of disaccharides... 

A monosaccharide obtained from dietary sources, either as the free sugar or as a part of the sucrose molecule. It is normally metabolized by the liver and kidney to glucose. Two inborn errors of fructose metabolism have been described ... 

An inborn error in which there is a defect in the metabolism of galactose. Galactose is normally metabolized to glucose via the following pathway. 

This monosaccharide can be both synthesized by the body and derived from dietary sources (especially from the disaccharide, lactose, where it constitutes one of the monosaccharide components). It is metabolized by the liver to glucose and glycogen. A failure to metabolize galactose occurs in the inborn error ol metabolism, galactosaemia. 

An inborn error of metabolism, characterized by the accumulation in the tissues of cerebrosides containing glucose residues. It is due to a deficiency of glucocerebrosidase which normally cleaves glucose from glucosyl ceramides. The disease is characterized by the accumulation of lipid-laden cells in the bone marrow and spleen. 

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