Organic acids in urine of patients with congenital lactic acidoses: An aid to differential diagnosis

Abstract

The differential diagnosis of patients with apparent congenital lactic acidoses poses one of the most intractable problems in the study of patients with disorders of organic acid metabolism. An outline of the factors leading to a lactic acidosis, particularly in infants and young children, together with a brief review of the known causes of congenital lactic acidosis, are presented. Quantitative examination of the organic acids excreted by patients with proven enzyme deficiencies causing congenital lactic acidosis has demonstrated the characteristic patterns that are associated with specific disorders of this kind. After exclusion of uninherited, acquired and secondary metabolic causes of lactic acidosis, the quantitative patterns of organic acid excretion, together with other clinical and biochemical observations, provide valuable indicators of the area of the underlying primary metabolic disorder for subsequent selected, confirmatory, enzymology. The study of organic acids has a key and central role in the approach to the clinical and biochemical investigation and diagnosis of patients with congenital lactic acidoses.

Glycerol‐3‐phosphate excretion in fructose‐1,6‐diphosphatase deficiency

“…had fructose-l,6-diphosphatase deficiency definitively diagnosed enzymatically by the total absence of this enzyme in her white blood cells. The raised urine excretion of lactate, pyruvate, 2-oxoglutarate and ~-hydroxybutyrate in this patient is consistent with observations previously reported in this condition (Chalmers, 1984). As similar organic acid abnormalities occur in glucose-6-phosphatase deficiency they do not lend themselves to differentiating between these two conditions (Chalmers, 1984).…”

Urinary Excretion of Lactate, 2-Oxoglutarate, Citrate, and Glycerol in Patients with Glycogenosis Type I

“…4), as tio (0) of patient MD with GSD-IA. Diet 1 at home; GDF during 12 h, has been found earlier (19). This finding does not tally with the irregular meals at daytime, total energy 2100 kcallday.…”

Feeding Problems and Lactic Acidosis in a 10-Week-Old Boy

“…El deficiency (pyruvate decarboxylase deficiency) can present as an acute neonatal disease with acidosis, as deterioration in psychomotor skills in a toddler, or as spinocerebellar atrophy in late adolescence; deficiency of this enzyme may account for some cases of Friedreich's ataxia [7]. In favor of a deficiency in this enzyme in our case is the fact that absence of the corpus callosum has been described with this defect [4], Against the diagnosis is the fact that with this enzyme missing, 2-oxoglutaric acid is elevated in the urine as the same enzyme is required to convert 2-oxoglutarate to succinyl CoA in the Kreb cycle [5]. Therefore, one would not expect urinary organic acids to be normal.…”

“…Ragged red fibers are expected in these defects, but our patient never had a muscle biopsy; at least 1 case of fatal infantile disease had normal liver mitochondria [15]. Normal urine or ganic acids are expected in defects involving the respira tory chain [5], so it seems possible that this baby could have an infantile myopathy related to a defect in the respiratory chain.…”