Hyperammonemia, hereditary

Symptoms of hereditary hyperammonemia include many of the neurologic manifestations of acquired hyperammonemia, but they are seen mainly in infants and frequently lead to mental retardation. 

The answer is B. All the findings are consistent with a diagnosis of hyperammonemia. A clue to its hereditary etiology is provided by the family history suggesting that the patient s sibling may have died of a similar condition. It is likely that the patient is suffering from a deficiency of one of the enzymes of the urea cycle the most common... 

A number of amino acid transport disorders may be associated with one or several of the systems described in Table 20.4. These are characterized by the excretion of amino acids in the urine but no increase in amino acid levels in the bloodstream. They are usually of hereditary origin. The most common disorder is cystinuria, characterized by the excretion of cystine. Because cystine is only slightly water soluble, cystinuria is often accompanied by the deposition of cystine-containing stones in the genitourinary tract. Cystinuria is apparently caused by a defect in the cationic amino acid transport system. Another disease that affects this system is lysinuric protein intolerance, which is associated with a failure to transport lysine, ornithine, arginine, and citrulline across membranes. Citrulline and ornithine are urea cycle intermediates (see later), and a disruption of their interorgan traffic results in hyperammonemia. 

Phenylketonuria Alcaptonuria Hyperammonemia I Hyperammonemia II McArdle s syndrome Hypophosphatasia Congenital lactase deficiency Hereditary fructose intolerance Gout... 

Hyperammonemia resulting from any of the enzymatic disorders of the biosynthesis of urea, must be distinguished from other conditions in which plasma ammonia is raised, sometimes sufficiently so to cause clinical manifestation. Severe liver disease as a primary cause of acquired hyperammonemia may be excluded from consideration since it is readily distinguishable from urea cycle defects. However, there are a number of other conditions described with hyperammonia as a prime manifestation, which because they show some clinical and biochemical similarity to hereditary enzyme defects of the urea cycle, have been claimed to be urea cycle disorders. 

Methylmalonyl-CoA mutase (EC 5.4.99.2). Failure to convert (/ )-methylmalonyl-CoA into succinyl-CoA. Large quantities of methylmalonic acid appear in plasma and urine. Affected children fail to thrive and show pronounced ketoacidosis. Often fatal in early life. Hyperammonemia and intermittent hyperglycinemia are also typical. Restricted protein intake and synthetic diets are helpful, in particular low intakes of leucine, isoleucine, valine, threonine and methionine. A similar condition may arise from a congenital deficiency of methylmalonyl-CoA epimerase (EC 5.1.99.1). Both conditions unresponsive to vitamin Bj2. Another type of methylmalonyl aciduria is thought to result from an hereditary deficiency of deoxyadenosyl transferase (transfers the 5 -deoxyade-nosyl group in cobalamin synthesis), which provides the coenzyme of methylmalonyl-CoA mutase. This condition responds to injection of B,2. Dietary B12 deficiency also results in methylmalonic aciduria. 

Seiler, N., C. Grauffel, G. Dauneanglard, S. Sarhan, and B. Knodgen, 1994. Decreased hyperammonemia and orotic aciduria due to inactivation of ornithine aminotransferase in mice with a hereditary abnormal ornithine carbamoyltransferase. J. Inherit. Metab. Dis. 17, 691-703. 

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