Unfavorable switching of skewed X chromosome inactivation leads to Menkes disease in a female infant.

Menkes disease is an X-linked disorder of copper metabolism caused by mutations in the ATP7A gene, and female carriers are usually asymptomatic. We describe a 7-month-old female patient with severe intellectual disability, epilepsy, and low levels of serum copper and ceruloplasmin. While heterozygous deletion of exons 16 and 17 of the ATP7A gene was detected in the proband, her mother, and her grandmother, only the proband suffered from Menkes disease clinically. Intriguingly, X chromosome inactivation (XCI) analysis demonstrated that the grandmother and the mother showed skewing of XCI toward the allele with the ATP7A deletion and that the proband had extremely skewed XCI toward the normal allele, resulting in exclusive expression of the pathogenic ATP7A mRNA transcripts. Expression bias analysis and recombination mapping of the X chromosome by the combination of whole genome and RNA sequencing demonstrated that meiotic recombination occurred at Xp21-p22 and Xq26-q28. Assuming that a genetic factor on the X chromosome enhanced or suppressed XCI of its allele, the factor must be on either of the two distal regions derived from her grandfather. Although we were unable to fully uncover the molecular mechanism, we concluded that unfavorable switching of skewed XCI caused Menkes disease in the proband.

High Plasma Presepsin Levels in Children With Hemophagocytic Lymphohistiocytosis.

Presepsin is reported as a novel diagnostic and prognostic biomarker for sepsis, and its optimal cutoff value is reported to be 600 to 650 pg/mL. Three children were diagnosed with hemophagocytic lymphohistiocytosis (HLH). The cause of HLH was unknown in cases 1 and 2, while Epstein-Barr virus infection was the cause in case 3. The plasma presepsin levels at the diagnosis were 1020, 1080, and 3160 pg/mL in cases 1, 2, and 3, respectively. In case 1, the plasma level of presepsin decreased to 164 pg/mL on day 19 of her sickness, when symptoms improved. Follow-up plasma presepsin levels were missing for cases 2 and 3. No microbiological pathogens were detected in the blood cultures of any of the patients. Our cases suggest that plasma presepsin levels can be elevated in childhood HLH.

Rapid blood cell recovery with immunosuppressive therapy combined with romiplostim in a patient with very severe hepatitis-associated aplastic anemia who underwent liver transplantation.

Patients with hepatitis-associated aplastic anemia (HAA) who undergo living-donor liver transplantation (LDLT) have a poor prognosis with infections and bleeding complications. Rapid recovery of blood cells is critical for preventing these complications and improving the outcome. Immunosuppressive therapy (IST) combined with thrombopoietin receptor agonists is considered effective for aplastic anemia. However, there are no data on the benefits of adding thrombopoietin receptor agonists to IST for HAA. We present the case of a child with severe HAA who underwent LDLT, and who achieved rapid blood cell recovery with IST combined with romiplostim, a thrombopoietin receptor agonist. In addition, despite having undergone LDLT, the patient had no adverse events such as serious liver dysfunction or thrombosis. This case suggests that IST combined with thrombopoietin receptor agonists may be a promising treatment option for HAA patients undergoing LDLT.