Clinical and molecular characteristics of two transaldolase-deficient patients

Abstract

Transaldolase (TALDO) deficiency is a rare metabolic disease in the pentose phosphate pathway, which manifests as a severe, early-onset multisystem disease. The body fluids of affected patients contain increased polyol concentrations and seven-carbon chain carbohydrates. We report the molecular and clinical findings in two recently diagnosed transaldolase-deficient children, both presented at birth. During infancy, they presented thin skin with a network of visible vessels, spider telangiectasias and multiple haemangiomas. Such unusual skin changes are characteristic of liver damage. Later, the patients developed rapidly progressive nodular liver fibrosis, tubulopathy and severe clotting disturbances. The clinical features of these patients were in line with previously studied patients with transaldolase deficiency. The diagnosis was established by detecting high concentrations of erythritol, ribitol, arabitol, sedoheptitol, perseitol, sedoheptulose and sedoheptulose-7-phosphate in the urine. Detection was made by gas chromatography and liquid chromatography-tandem mass spectrometry and then confirmed by molecular analysis of the TALDO gene. Conclusion: Transaldolase deficiency, a rare early-onset multisystem disease, should be considered by neonatologists, paediatricians, hepatologists and nephrologists in the differential diagnosis of patients presenting hepatosplenomegaly, thrombocytopenia, anaemia, bleeding diathesis, liver failure and tubulopathy.

Unexpected roles for ADH1 and SORD in catalyzing the final step of erythritol biosynthesis

“…1) (3). In a recent case report, deficiency in the PPP enzyme transaldolase (TALDO) was accompanied by high concentrations of polyols including erythritol, ribitol, and sedoheptitol in the urine, supporting the link between erythritol production and the PPP (6). Although the metabolic pathway for erythritol synthesis is now recognized to be active in humans, the identity of the enzyme(s) catalyzing the conversion of erythrose to erythritol remains unknown.…”

Long-Term Systematic Monitoring of Four Polish Transaldolase Deficient Patients

“…Anemia, thrombocytopenia, slightly elevated transaminases, and bleeding diathesis were still noted. Sugars and polyols were measured, revealing elevated excretion in the urine (Tylki-Szymanska et al 2014). A homozygous deletion c.462-174_981+53del in the TALDO1 gene was identified.…”

“…A homozygous deletion c.462-174_981+53del in the TALDO1 gene was identified. This deletion spans 1,317 bps and alters the acceptor splice site of exon 5 (Tylki-Szymanska et al 2014).…”

“…At the age of 15 months, urinary sugars and polyols were measured, and the profile suggested TALDO deficiency (Tylki-Szymanska et al 2014). Molecular analysis revealed two mutations (c.575G>A, c.462-174_981+53del) in the TALDO1 gene.…”

Hepato- and splenomegaly in selected metabolic diseases – diagnostics and differentiation

“…W wybranych schorzeniach metabolicznych, np. w chorobie Niemanna-Picka typu C czy deficycie transaldolazy (zaburzenie przemiany pentoz), znaczne powiększenie śledziony może występować już w okresie noworodkowym [6][7][8].…”