Transaldolase Deficiency: A New Case Expands the Phenotypic Spectrum

Abstract

Transaldolase (TALDO) deficiency has various clinical manifestations including liver dysfunction, hepatosplenomegaly, anemia, thrombocytopenia, and dysmorphic features. We report a case presenting prenatally with hyperechogenic bowel and intrauterine growth restriction. The infant was born small for gestational age, with cutis laxa and hypertrichosis. Postnatally, meconium plug was identified, complicated with intestinal obstruction necessitating laparotomy, partial resection of the intestine, and ileostomy. Liver biopsy revealed cholangiolar proliferation and portal fibrosis. He also suffered from persistent congenital thrombocytopenia requiring platelet transfusions and severe hypothyroidism with normal anatomical and structural gland responding only to the combination of T3 and T4 treatment. Neurologically, severe hypotonia and anisocoria were noted at the age of 2 months. Brain MRI was normal. Shortly after the abdominal surgery, a rapid liver failure ensued, which eventually led to his death. Specific metabolic tests ruled out glycosylation disorders, yet urine analysis using 1H NMR showed accumulation of sedoheptulose which was previously described in patients with transaldolase deficiency. Sequencing of the gene-encoding transaldolase (TALDO1) revealed a homozygous stop mutation c.669C>G; p.Tyr223*. In conclusion, we present an infant with a novel homozygous mutation in TALDO1, causing TALDO deficiency, and extend the clinical characteristics of this rare syndrome.

Keywords: Cutis laxa; Echogenic bowel; Hypothyroidism; Microarray analysis; Transaldolase.

Fig. 1

TALDO deficiency in the patient. (a) TALDO1 homozygous pathogenic mutation c.669C>G; p.Tyr223* in the patient and his parents. Sanger sequencing of the patient and his parents: both parents are heterozygous for the mutation and a wild-type allele. TALDO1 mutation is not found in controls of the same background (not included). (b) A 1H-NMR spectrum of the patient urine sample showing abnormally high levels of sugars at about 3.3–4.5 ppm. Sedoheptulose (a ketoheptose) was identified using the S1, S3, and S4 signals of sedoheptulose which were previously characterized in a urine sample from a patient with TALDO deficiency (Engelke et al. 2010). Erythronic acid was not detected in the patient’s urine, as depicted by the lack of the characteristic doublet signal at 4.325 (position marked E2) (Engelke et al 2010). (c) TALDO1 gene cDNA schematic structure. Mutations are presented on the diagram. The following are the mutations previously described: c.512_514delCCT, p.Ser171del; c.512C>T, p.Ser171Phe; c.574C>T, p.Arg192Cys; c.575G>A, p.Arg192His; c.793delC, p.Gln265ArgfsX56; c.895_897delAAC, p.Asn299del; c.931G>A, p.Gly311Arg; c.462-174_981+53del. The mutation in the patient described in this article is colored in red