The Dicarboxylic Acidurias

The genetically determined defect of membrane carnitine transport is the only known condition that fulfills the criteria for primary carnitine deficiency [4, 9]. This condition, like the other conditions involving the carnitine cycle, is not associated with dicarboxylic aciduria. It is... 

A few patients have been described with a defect involving the carnitine-acylcarnitine translocase system, which facilitates the movement of long-chain acylcarnitine esters across the inner membrane of the mitochondrion (Fig. 42-2). These patients have extremely low carnitine concentrations and minimal dicarboxylic aciduria [4]. 

Carnitine uptake defect (CUD, 14.1) is due to a defect in the high-affinity carnitine transporter [1]. Plasma free and total carnitine levels are extremely low. Clinically two forms exist an early childhood-onset cardiomyopathic form and a hepatic form with recurrent crises of Reye-like syndrome. In general the response to oral carnitine supplements is very good. Plasma acylcarnitines are normal, there are scattered reports on moderate dicarboxylic aciduria. 

CPTl deficiency (14.2) has only hepatic involvement cardiomyopathy is absent. The clinical presentation is rather homogenous with recurrent episodes of hepatic dysfunction, often accompanied by hypoglycemia. Many patients develop renal tubular acidosis (unexplained) [2]. This is one of the defects in which the mother of a patient may experience acute fatty liver of pregnancy [3]. Plasma-free carnitine is reportedly increased, but normal values have been observed. Dicarboxylic aciduria is a rarity. 

Three forms of VLCAD deficiency (14.5) are known, i.e. a (lethal) neonatal cardiomyopathic form, a childhood form with recurrent Reye-like episodes, and an adolescent/adult muscular form [6]. The latter may be accompanied by severe rhabdomyolysis and sometimes renal failure. Diagnostic criteria are the abnormal plasma acylcarnitine and organic acid profile (Ci4 i, Ci4 2 and Ci6 i) and the Cg-Cio dicarboxylic aciduria, especially in young patients. 

Carnitine and its esters (see [1]) cannot be introduced to the mass spectrometer by gas chromatography, as they incorporate quaternary amine functions and will decompose in the attempt. Fast atom bombardment (FAB) and electrospray ionization (ESI) can use the formal charge on the quaternary amine function to advantage, as carnitine and its esters are very easily desorbed from glycerol on the FAB probe and from aerosol sprays in ESI. Eigure 7A illustrates the use of EAB in the quantitation of carnitine and its esters excreted in the urine of a patient presenting with a severe dicarboxylic aciduria associated with medium-chain acyl-CoA dehydrogenase (MCAD) deficiency. 

Gregersen, N., Lauritzen, R. and Rasmussen, K. (1976), Suberylglycine excretion in the urine from a patient with dicarboxylic aciduria. Clin. Chim. Acta, 70,417. 

The dissimilarity of these patients from those with apparent multiple acyl-CoA dehydrogenase deficiency (Section 14.2.1) and other dicarboxylic acidurias is noticeable and the primary defect remains unknown. 

Chalmers, R. A. and Lawson, A.M. (1979), Identification of 5-hydroxyhexanoic acid in the urine of twin siblings with a Reye s-like syndrome associated with dicarboxylic aciduria and hypoglycaemia and with similarities to Jamaican Vomiting Sickness. Biomed. Mass Spectrom., 6,444. 

---