A Rare Cause of Hypergonadotropic Hypogonadism: Transaldolase Deficiency in Two Siblings.

Transaldolase deficiency is a rare inborn autosomal recessive disorder caused by biallelic mutations in the TALDO1 gene. It is characterized by intrauterine growth restriction, dysmorphism, cytopenia, hepatosplenomegaly, liver cirrhosis, endocrine problems, and skin, renal and cardiac abnormalities. We present two siblings of Turkish origin with an early-onset form of transaldolase deficiency and hypergonadotropic hypogonadism in both sexes. The girl (index) was followed-up for cryptogenic cirrhosis, leukopenia and thrombocytopenia, skin abnormalities, congenital heart defects, hypercalciuria, nephrolithiasis, proteinuria, and chronic kidney disease throughout childhood. She developed hypergonadotropic hypogonadism in adolescence. Whole exome sequencing due to the multisystemic involvement revealed a previously described homozygous, inframe deletion in TALDO1. Her brother was born small for gestational age and was also followed-up with cryptogenic cirrhosis from infancy, together with cytopenia, congenital heart defects, bilateral cryptorchidism, short stature, hypercalciuria, proteinuria and chronic kidney disease in childhood. He presented with testicular microlithiasis and hypergonadotropic hypogonadism in adolescence. Sanger sequencing of TALDO1 confirmed the presence of the same homozygous deletion as his sister. The mother was found to be a heterozygous carrier for this deletion. We describe two patients with multisystemic involvement since the neonatal period who presented with additional hypergonadotropic hypogonadism in adolescence. The diagnosis of transaldolase deficiency should be kept in mind for these patients, and they must be evaluated for gonadal functions, especially during puberty.