Transaldolase Deficiency

A number sign (#) is used with this entry because of evidence that transaldolase deficiency is caused by homozygous or compound heterozygous mutation in the TALDO1 gene (602063) on chromosome 11p15.

Description

Transaldolase deficiency is a rare inborn error of pentose metabolism. Typical features include intrauterine growth restriction, triangular vase, loose wrinkly skin at birth, and development of progressive liver failure (summary by Lee-Barber et al., 2019).

Clinical Features

Verhoeven et al. (2001) described deficiency of transaldolase in the first child of healthy, consanguineous Turkish parents. Soon after birth, the patient had undergone surgical correction of aortic coarctation. Within several months, she developed hepatosplenomegaly. Elevated concentrations of ribitol, D-arabitol, and erythritol were found in urine and plasma. At the age of 10 years, the patient showed many telangiectases of the skin, hepatosplenomegaly, and enlarged clitoris. She had persistent thrombocytopenia which was thought to be caused by splenic pooling due to the hepatosplenomegaly. A deficiency of transaldolase was discovered by incubating the patient's lymphoblasts and erythrocytes with ribose-5-phosphate and subsequently analyzing phosphate sugar metabolites.

Eyaid et al. (2013) reported 12 cases of transaldolase deficiency from 6 families who were followed for 8 years. All 12 patients had cardiac defects, wrinkly skin, and dysmorphic facial features characterized by triangular face, low-set ears, prominent philtrum, infraorbital creases, wide mouth, and thin lips. All had hepatosplenomegaly, anemia, and thrombocytopenia. Seven of 12 had liver dysfunction. Poor growth was quite common. Cardiac defects included patent ductus arteriosus (PDA) and persistent foramen ovale (PFO). One patient (patient 2, family 3) had dextrocardia with moderate PDA; he also had situs inversus totalis and mild right hydronephrosis. Urine samples from 8 patients were analyzed for polyols, heptuloses, and sedoheptulose-7P. In all urine samples, elevated excretion of erythritol, ribitol, arabitol, sedoheptitol, perseitol, sedoheptulose, mannoheptulose, and sedoheptulose-7P were detected, consistent with transaldolase deficiency. The sugar phosphates ribose-5-P and xylulose (+ribulose)-5P were also highly elevated in urine. Plasma samples received from 9 patients showed elevated concentrations of the polyols erythritol, arabitol, and ribitol. Eyaid et al. (2013) remarked that cutis laxa and dysmorphism were most notable in the neonatal period but appeared to be less recognizable after infancy, whereas the bleeding tendency and liver involvement followed a more irregular course that waxed and waned but was very severe in some.

Lee-Barber et al. (2019) reported a 13-month old boy with transaldolase deficiency who developed mild liver failure after receiving standard doses of acetaminophen during a respiratory infection. At birth and throughout the first year of life, the boy had a bronzed, aged appearance with minimal subcutaneous fat, prominent wrinkles in the skin of his hands, visible scalp veins, large abdomen without reported hepatomegaly, and thin extremities. After receiving standard doses of acetaminophen, he was found to have neutropenia, thrombocytopenia, and an enlarged nodular liver with accompanying splenomegaly as well as rising alpha-fetoprotein levels, which peaked 2 weeks after acetaminophen exposure. After discontinuation of acetaminophen, his elevated alpha-fetoprotein levels resolved, suggesting that acetaminophen had initiated the liver failure.

Molecular Genetics

By sequence analysis of the TALDO1 gene in a patient with transaldolase deficiency, Verhoeven et al. (2001) identified a homozygous 3-bp deletion, resulting in the absence of serine at position 171 of the transaldolase protein (602063.0001).

In all 12 patients studied with transaldolase deficiency, Eyaid et al. (2013) identified homozygosity for a frameshift mutation in the TALDO1 gene (602063.0002).

By whole-exome sequencing in a 13-month-old boy with transaldolase deficiency, Lee-Barber et al. (2019) identified compound heterozygosity for the previously identified 3-bp deletion (602063.0001) and a missense mutation (G311W; 602063.0003) in the TALDO1 gene. Each parent was heterozygous for one of the mutations.