Neonatal cholestasis

Gene: TALDO1

Comment on list classification: Presumed pathogenic variants in TALDO1 have been reported in 34 cases from 25 families. 11 variants have been reported, most of which are homozygous in affected individuals, who are usually from consanguineous families. One variant, c.574C>T (p.R192C), is thought to show a founder effect although haplotype analysis has not been carried out. Biochemical analysis (urine polyols and/or TALDO activity) was carried out in the majority of cases and was supportive of a pathogenic effect of the variants in all cases. Phenotypic variability is reported, however liver cirrhosis (with or without deranged liver function) was present in a significant proportion of cases, particularly those which presented neonatally (77%). Liver dysfunction in TALDO1 deficiency does not seem to be typically associated with cholestasis, however the clinical presentation is often with neonatal liver dysfunction, which is included in the scope of this panel.

Created: 29 Aug 2018, 8:55 a.m.

Genomics England clinical team have confirmed that Transaldolase deficiency is relevant to the neonatal cholestasis panel.

Created: 3 Sep 2018, 8:30 p.m.

Checking with Genomics England clinical team of relevance of the Transaldolase deficiency to this panel.

Created: 16 Aug 2018, 8:37 a.m.

Comment on publications: Added publications from OMIM

Created: 16 Aug 2018, 8:35 a.m.

In OMIM TALDO1 is associated with Transaldolase deficiency. Evidence comes from Verhoeven et al. (2001) (PMID: 11283793) who report deficiency of transaldolase in the first child of healthy, consanguineous Turkish parents. The patient presented with liver cirrhosis and hepatosplenomegaly during early infancy. A homozygous 3-bp deletion, resulting in the absence of serine at position 171 of the transaldolase protein was identified. Eyaid et al. (2013) (PMID: 23315216) reported 12 cases of transaldolase deficiency from 6 families. All had a single-bp deletion at c.793delC, which resulted in a frameshift with premature termination. All patients had multiple clinical features including hepatosplenomegaly, anemia, and thrombocytopenia. Seven of 12 had liver dysfunction. All 12 cases were diagnosed as children.

Created: 16 Aug 2018, 8:35 a.m.

I don't know

Comment on mode of inheritance: added MOI from literature and OMIM

Created: 27 Jul 2018, 10:19 a.m.

Comment on phenotypes: added phenotypes from OMIM

Created: 27 Jul 2018, 10:19 a.m.

TALDO1 is on the King's College Hospital NHS Foundation Trust diagnostic cholestasis gene panel for Transaldolase deficiency.

Created: 25 Jul 2018, 4:25 p.m.