ABSTRACT. Concentrations of I-carnitine and acylcarnitines have been determined in urine from patients with disorders of organic acid metabolism associated with an intramitochondrial accumulation of acyl-CoA intermediates. These included propionic acidemia, methylmalonic aciduria, isovaleric acidemia, multicarboxylase deficiency, 3-hydroxy-3-methylglutaric aciduria, methylacetoacetylCoA thiolase deficiency, and various dicarboxylic acidurias including glutaric aciduria, medium-chain acyl-CoA dehydrogenase deficiency, and multiple acyl-CoA dehydrogenase deficiency. In all cases, concentrations of acylcarnitines were greatly increased above normal with free carnitine concentrations ranging from undetectable to supranorma1 values. The ratios of acylcarnitinelcarnitine were elevated above the normal value of 2.0 f 1.1. I-Carnitine was given to three of these patients; in each case, concentrations of plasma and urine carnitines increased accompanied by a marked increase in concentrations of short-chain acylcarnitines. These acylcarnitines have been examined using fast atom bombardment mass spectrometry in some of these diseases and have been shown to be propionylcarnitine in methylmalonic aciduria and propionic acidemia, isovalerylcarnitine in isovaleric acidemia, and hexanoylcarnitine and octanoylcarnitine in medium-chain acyl-CoA dehydrogenase deficiency. The excretion of these acylcarnitines is compatible with the known accumulation of the corresponding acyl-CoA esters in these diseases.In this group of disorders, the increased acylcarnitinel carnitine ratio in urine and plasma indicates an imbalance of mitochondria1 mass action homeostasis and, hence, of acyl-CoAICoA ratios. Despite naturally occurring attempts to increase endogeneous I-carnitine biosynthesis, there is insufficient carnitine available to restore the mass action ratio as demonstrated by the further increase in acylcarnitine excretion when patients were given oral I-carnitine. Thus, I-carnitine insufficiency is a general phenomenon in these diseases. ( Roe and Bohun (15) observed absence of free I-carnitine in urine of a patient with propionic acidemia (propionyl-CoA carboxylase deficiency), with favorable clinical responses to I-carnitine challenge and treatment. This observation prompted reports of reduced plasma free carnitine in patients with a variety of other metabolic disorders (1, 16) and Seccombe et al. (1 8) also reported increased acylcarnitine to carnitine ratios in a patient with methylmalonic aciduria. Similar observations of reduced plasma carnitine and increased acylcarnitine excretion in a patient with multiple acyl-CoA dehydrogenation defects ("glutaric aciduria type 11") have been made (I I). The importance of measurement of acylcarnitine concentrations in such conditions was undeqlined by the observation that under ketotic conditions acylcarnitine concentrations increase at the expense of free carnitine (12). This suggests that a shift in mitochondrial metabolite ratios and mass action homeostasis occurs under these circumstance...

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In order to obtain an estimate of the frequency of platelet-specific and granulocyte-specific antibodies and of the effect of such antibodies on the platelet count and granulocyte count of the newborn infant, serum from 147 women in their second or subsequent pregnancies was tested. No platelet-specific antibodies were found but 29 of the women had granulocyte-specific antibodies and the corresponding infants had granulocyte counts which were significantly lower than those of infants without antibodies. HLA antibodies were found in the sera of 57 women but were not associated with diminished platelet or granulocyte counts in the corresponding infants. Maternal granulocyte antibodies may be an underestimated contributory factor in the pathogenesis of neonatal neutropenia.