Hypoglycaemia deficiency

Box 7.2 A deficiency of the hepatic glycogen store hypoglycaemia and ketosis in a child... 

Children with a primary deficiency of the carnitine transporter present with acute episodes of hypoglycaemia leading to loss of consciousness during even a short fast. (See Chapter 9 for a role of carnitine) in the Krebs cycle. 

Baker L, Winegrad AI (1970) Fasting hypoglycaemia and metabolic acidosis associated with deficiency of hepatic fructose-1,6-diphosphatase activity. Lancet ii 13 16... 

The adrenal cortex secretes steroid hormones, primarily glucocorticoids and mineralocorticoids. Deficiency of these steroids results in Addison s disease, characterized by hypoglycaemia, lethargy and weight loss, anorexia and nausea and hypotension, which can be severe and may result in cardiovascular collapse. Treatment includes replacement of the missing steroids. 

Primary carnitine deficiency is caused by a deficiency in the plasma-membrane carnitine transporter. Intracellular carnitine deficiency impairs the entry of long-chain fatty acids into the mitochondrial matrix. Consequently, long-chain fatty acids are not available for p oxidation and energy production, and the production of ketone bodies (which are used by the brain) is also impaired. Regulation of intramitochondrial free CoA is also affected, with accumulation of acyl-CoA esters in the mitochondria. This in turn affects the pathways of intermediary metabolism that require CoA, for example the TCA cycle, pyruvate oxidation, amino acid metabolism, and mitochondrial and peroxisomal -oxidation. Cardiac muscle is affected by progressive cardiomyopathy (the most common form of presentation), the CNS is affected by encephalopathy caused by hypoketotic hypoglycaemia, and skeletal muscle is affected by myopathy. 

Growth hormone deficiency may be present from birth or due to later pituitary-failure. A variety of stimulation tests have been used to evaluate GH deficiency. Seram GH concentrations rise in response to exercise, and this may be u.sed as a preliminary screening test. They also rise during sleep, and high concentrations in a nocturnal sample may exclude GH deficiency. The lack of GH response to clonidine, a potent stimulant of GH secretion, isdiagnostic. Some centres have now abandoned the use of insulin-induced hypoglycaemia as a diagnostic test in children because of its hazards. 

MCAD deficiency is the most common defect of P-oxidation in humans. It is an autosomal, recessively-inherited, potentially fatal disease, usually manifesting within the first years of life. The clinical manifestations can be quite diverse, but usually include fasting-induced non-ketotic hypoglycaemia, lethargy, even coma. Up to 25% of the first of such attacks can be fatal, although affected individuals who remain symptom free for years have also been reported. " The wide clinical spectrum is partially due to the fact that fasting, sometimes in connection with infection and fever, is required to trigger the disease. 

Figure 26.4 GSD III, Cori s disease. This is named after husband and wife, Carl and Gerty Cori (so note the apostrophe if you prefer Coris s disease). GSD III is caused by a deficiency of debranching enzyme so liinit dextrin accumulates, which is an abnormal form of glycogen where the branches are reduced to a-(l —>6) stumps. GSD III presents with hypoglycaemia and hepatomegaly.

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.

In carnitine deficiency, fatty acids cannot enter the mitochondrion. Consequently 3-oxidation is inhibited, resulting in hypoglycaemia. 

Deficiency Biotin deficiency is unusual on a normal diet. However, in the late 1970s biotin deficiency in infants was implicated as a possible cause of sudden infant death syndrome, ft was proposed that biotin deficiency nsstric ted gluconeogenesis causing fetal hypoglycaemia. 

MCAD deficiency. The most frequent inborn error of fatty acid oxidation (1 12000 to 20000 in Caucasians from northern Europe). It affects the medium chain acyl-CoA dehydrogenase and in around 80% of the affected alleles a single common missense mutation has been identified. Symptoms typically appear during infancy or early childhood and can include vomiting, lethargy and hypoglycaemia. 

Since the first report of CAC deficiency (OMIM entry 212138) by Stanley et al., 1 cases have been reported. Most patients suffer from hypoketotic hypoglycaemia and... 

Destruction of the adrenal cortex results in a deficiency of glucocorticoids, mineralocorticoids and androgens, and the features of the disease are a reflection of this. Mineralocorticoid deficiency leads to sodium deficiency, which in turn leads to dehydration and this can present as an Addisonian crisis. The deficiency of glucocorticoids leads to hypoglycaemia and pronounced insulin sensitivity with a flat glucose tolerance curve. Because of the glucocorticoid deficiency, the pituitary produces maximal... 

Hereditary fructose intolerance which is a more serious condition in which there are metabolic disturbances, e.g. hypoglycaemia, after fructose ingestion. It is due to a deficiency of the enzyme fructose-1-phosphate aldolase. 

Biotin. Biotin deficiency blocks pyruvate carboxylase resulting in an accumulation of pyruvate and lactate. It suppresses gluconeogenesis and causes fasting hypoglycaemia. 

Glycerol is used as a therapeutic agent to reduce elevated intracranial and intraocular pressure and, until recently, was considered safe for oral and intravenous use. However, children with hepatic fructose-1,6-diphosphatase deficiency may develop lactic acidosis and hypoglycaemia after the use of glycerol. In adults, 20% glycerol in isotonic saline has caused haemolysis, haemoglobinuria and acute renal failure (42). 

Schutgens, R.B.H., Wadman, S.K. and Duran, M. (1978), Severe lethal hypoglycaemia in a child due to deficiency of 3-hydroxy-3-methylglutaryl coenzyme A lyase. Proc. Ann. Meet. Soc. Study Inborn Errors Metab. 16th, Bristol, July, 1978. 

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