title: A newborn with severe liver failure, cardiomyopathy and transaldolase deficiency.
abstract: 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.
authors.affiliation: Metabolic Laboratory, Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands. n.verhoeven@vumc.nl
authors.forename: N M
authors.initials: NM
authors.lastname: Verhoeven
authors.forename: M
authors.initials: M
authors.lastname: Wallot
authors.forename: J H J
authors.initials: JH
authors.lastname: Huck
authors.forename: O
authors.initials: O
authors.lastname: Dirsch
authors.forename: A
authors.initials: A
authors.lastname: Ballauf
authors.forename: U
authors.initials: U
authors.lastname: Neudorf
authors.forename: G S
authors.initials: GS
authors.lastname: Salomons
authors.forename: M S
authors.initials: MS
authors.lastname: van der Knaap
authors.forename: T
authors.initials: T
authors.lastname: Voit
authors.forename: C
authors.initials: C
authors.lastname: Jakobs
mesh_terms: D009202:Cardiomyopathies / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000175:diagnosis / Q000209:etiology / Q000235:genetics; D017114:Liver Failure, Acute / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism; D008661:Metabolism, Inborn Errors / Q000150:complications* / Q000175:diagnosis / Q000235:genetics; D009005:Monosaccharides / Q000652:urine; D020125:Mutation, Missense; D011108:Polymers / Q000378:metabolism; D012720:Severity of Illness Index; D014153:Transaldolase / Q000172:deficiency / Q000235:genetics*
chemical_list: D009005:Monosaccharides; D011108:Polymers; C024617:polyol; D014153:Transaldolase