A newborn with severe liver failure, cardiomyopathy and transaldolase deficiency.

This paper describes the second patient found to be affected with a deficiency of transaldolase (TALDO1; EC 2.2.1.2). Clinically, this patient presented in the neonatal period with several signs of severe liver failure: severe coagulopathy, low serum protein, elevated blood ammonia, and hypoglycaemia. She had generalized oedema, moderate muscular hypotonia, and dysmorphic signs. Liver size was decreased, and the spleen was moderately enlarged. There was severe cardiomegaly. The clinical course was characterized by intractable liver failure and progressive myocardial hypertrophy. The child died at the age of 18 days from respiratory failure. In urine, elevations of erythritol, arabitol and ribitol were found, suggesting a deficiency of transaldolase. Enzyme studies in cultured fibroblasts showed undetectable transaldolase activity. DNA sequence analysis of the TALDO1 gene showed a homozygous missense mutation (575G>A), resulting in an amino acid alteration at position 192 (arginine to histidine, R192H). This amino acid is part of the catalytic site of the transaldolase protein. Discovery of this second patient affected with transaldolase deficiency and liver failure suggests that this disorder has a heterogeneous clinical presentation with highly variable severity.

Clinical presentations of patients with polyol abnormalities.

Since our description of a patient with leukoencephalopathy and highly elevated polyols in the brain and body fluids, we started screening for polyol abnormalities in patients highly suspected of a metabolic disorder. We identified four additional patients with consistent abnormalities in sugar and polyol profiles in body fluids. The clinical, neuroimaging, and biochemical findings of the five patients detected so far are described in the present paper. In four patients neurological problems dominated the clinical picture, whereas liver failure dominated in the other patient. The sugar and polyol profiles were abnormal in body fluids in all patients, but the profiles were different in individual patients. A deficiency of transaldolase was found in the patient presenting with liver failure. We were not able to identify the basic defect in the four patients with predominantly neurological problems. The differences in clinical picture, MRI abnormalities, and sugar and polyol profiles in these patients suggest that the underlying defects may be different. Whether the abnormal sugar and polyol profiles are directly related to the cause of disease via defects in polyol metabolism or transport remains to be elucidated.

Transaldolase deficiency: liver cirrhosis associated with a new inborn error in the pentose phosphate pathway.

This article describes the first patient with a deficiency of transaldolase (TALDO1 [E.C.2.2.1.2]). Clinically, the patient presented with liver cirrhosis and hepatosplenomegaly during early infancy. In urine and plasma, elevated concentrations of ribitol, D-arabitol, and erythritol were found. By incubating the patient's lymphoblasts and erythrocytes with ribose-5-phosphate and subsequently analyzing phosphate sugar metabolites, we discovered a deficiency of transaldolase. Sequence analysis of the transaldolase gene from this patient showed a homozygous deletion of 3 bp. This deletion results in absence of serine at position 171 of the transaldolase protein. This amino acid is invariable between species and is located in a conserved region, indicating its importance for enzyme activity. The detection of this new inborn error of pentose metabolism has implications for the diagnostic workup of liver problems of unknown etiology.

Achieving high-quality comprehensive dentistry with i.v. sedation.

This comprehensive approach requires a high-tech/touch staff environment and a dedication to excellence in all areas of patient care. Its rewards are financial and personal because it creates a highly satisfied and appreciative patient.