Chronic steroid‐response pancytopenia and increased bone density due to thromboxane synthase deficiency

Abstract

Diagnosis of bone marrow failure (BMF) disorders is challenging but essential for optimal patient management. Here, we report a young adult from nonconsanguineous parents with progressive pancytopenia since childhood, bone pain, increased bone density, and haphazard ossification replacing hematopoiesis within the bone marrow. Sequencing revealed two novel biallelic variants of unknown significance within the thromboxane A synthase gene, TBXAS1 (c.266T > C; c.989T > C), bioinformatically predicted to disrupt the protein. TBXAS1 mutations result in Ghosal hematodiaphyseal dysplasia (OMIM 231095), the autosomal recessive syndrome associated with abnormal bone structure and BMF. Identification of the genetic defect prompted steroid therapy leading to resolution of symptoms.

Ghosal Hematodiaphyseal Dysplasia: A Case Report

“…Elevated PGE2 may suppress erythroid precursor cells, resulting in refractory anemia seen in GHDD patients. It is also suggested that TXAS and TXA2 may also play a key role in bone remodeling as PGE2 that can stimulate both bone resorption and formation 2,7,8 . Progressive diaphyseal dysplasia (PDD) also known as Camurati-Engelmann disease is a close radiologic differential diagnosis of GHDD.…”

Bone fragility in patients affected by congenital diseases non skeletal in origin

“…Severe congenital neutropenia (SCN) patients are affected by congenital severe neutropenia, with an absolute neutrophil count (ANC) of less than 0.2 × 10 9 /L [ 115 ]. Bone marrow examination in the majority of cases reveals a maturation arrest of myelopoiesis at the level of promyelocytes, which generally leads to reduced neutrophil counts but increased numbers of atypical promyelocytes.…”

“…Bone marrow examination in the majority of cases reveals a maturation arrest of myelopoiesis at the level of promyelocytes, which generally leads to reduced neutrophil counts but increased numbers of atypical promyelocytes. In these patients, the risk of infections such as otitis, gingivitis, skin infections, pneumonia, deep abscesses and septicemia begins in the neonatal period [ 115 ]. Furthermore, patients with severe congenital neutropenia have an increased risk of developing leukemia [ 115 ] .…”

“…In these patients, the risk of infections such as otitis, gingivitis, skin infections, pneumonia, deep abscesses and septicemia begins in the neonatal period [ 115 ]. Furthermore, patients with severe congenital neutropenia have an increased risk of developing leukemia [ 115 ] . The prevalence of SCN is estimated to be 3–8.5 cases per million individuals.…”

“…Demographics play an important part in epidemiology. Worldwide, autosomal dominant disorders seem to be more common, whereas the recessive disorders are usually diagnosed in consanguineous kindreds [ 115 ]. Several genes can be involved in severe congenital neutropenia and play a role in the maturation and function of neutrophils, promoting cell survival and response to immune signals.…”