Hypergonadotropic Hypogonadism Due to Transaldolase Deficiency: Two Cases and Literature Review.

Transaldolase deficiency is a rare autosomal recessive inborn error of carbohydrate metabolism caused by pathogenic/likely pathogenic biallelic mutations in the gene. This disorder is characterized by multisystem involvement with variable phenotypes, including intrauterine growth restriction; dysmorphic features; abnormal skin; hepatosplenomegaly; cytopenia; and cardiac, renal, and endocrine abnormalities. Herein, we present two Emirati patients with hypergonadotropic hypogonadism due to transaldolase deficiency and variable phenotypes of systemic involvement.

mTOR-dependent loss of PON1 secretion and antiphospholipid autoantibody production underlie autoimmunity-mediated cirrhosis in transaldolase deficiency.

Transaldolase deficiency predisposes to chronic liver disease progressing from cirrhosis to hepatocellular carcinoma (HCC). Transition from cirrhosis to hepatocarcinogenesis depends on mitochondrial oxidative stress, as controlled by cytosolic aldose metabolism through the pentose phosphate pathway (PPP). Progression to HCC is critically dependent on NADPH depletion and polyol buildup by aldose reductase (AR), while this enzyme protects from carbon trapping in the PPP and growth restriction in TAL deficiency.

Pathologic and Immunophenotypic Characterization of Syncytial Giant Cell Variant of Pediatric Hepatocellular Carcinoma. A Distinct Subtype.

Introduction: Hepatocellular carcinoma (HCC) in pediatrics has a uniformly poor prognosis. Complete surgical resection or liver transplantation remain the only curative options. In contrast to adult HCC, literature on pediatric HCC is sparse and a majority of the distinct subtypes are undefined with regards to their histology, immunohistochemistry and prognosis.