Hepatitis and Vasodilatory Shock due to an Unsuspected Culprit: A Rare Presentation of Multisystem Langerhans Cell Histiocytosis

Introduction: Langerhans cell histiocytosis (LCH) is a rare hematologic condition which can affect multiple organ systems and has variable presentation. LCH is more commonly seen as a malignancy of childhood. LCH in adulthood can have poor outcomes depending on the involvement of critical organs. Case Presentation: We report a case of a 71-year-old female who presented with progressive weakness, weight loss, diarrhea, and jaundice, and had been undergoing outpatient workup for elevated liver enzymes for the last 2 years. She required admission to the intensive care unit for vasodilatory shock, requiring vasopressor and chronotropic support. Imaging showed an underlying multiorgan process involving the gastrointestinal tract, liver, spleen, and central nervous system. A repeat liver biopsy after a prior inconclusive one revealed the diagnosis of multisystem LCH presenting as secondary sclerosing cholangitis. Conclusion: The uniqueness of this multisystem LCH case lies not only in its rarity but also in the diagnostic journey that necessitated a repeat biopsy for a conclusive diagnosis. Early identification and targeted intervention can help in ensuring better patient outcomes, especially when the presentation can overlap with various other possible conditions

Nonconvulsive status epilepticus secondary to acute porphyria crisis

Both variegate and acute intermittent porphyria can manifest with various neurological symptoms. Although acute symptomatic seizures have been previously described, they are typically tonic–clonic and focal impaired awareness seizures. Convulsive status epilepticus and epilepsia partialis continua are rare and have been described on a case report basis. To our knowledge, there are no previously reported cases describing non-convulsive status epilepticus (NCSE) with electroencephalogram (EEG) documentation in the setting of acute porphyria crisis. We report a unique presentation of NCSE, which resolved after administering levetiracetam in a patient with variegate porphyria, without a known seizure disorder. Keywords: Variegate porphyria, Non-convulsive status epilepticus, Electroencephalogram, Anticonvulsant medication, Acute porphyria crisi

A SUMO-ubiquitin relay recruits proteasomes to chromosome axes to regulate meiotic recombination

Meiosis produces haploid gametes through a succession of chromosomal events, including pairing, synapsis, and recombination. Mechanisms that orchestrate these events remain poorly understood. We found that the SUMO (small ubiquitin-like modifier)-modification and ubiquitin-proteasome systems regulate the major events of meiotic prophase in mouse. Interdependent localization of SUMO, ubiquitin, and proteasomes along chromosome axes was mediated largely by RNF212 and HEI10, two E3 ligases that are also essential for crossover recombination. RNF212-dependent SUMO conjugation effected a checkpointlike process that stalls recombination by rendering the turnover of a subset of recombination factors dependent on HEI10-mediated ubiquitylation. We propose that SUMO conjugation establishes a precondition for designating crossover sites via selective protein stabilization. Thus, meiotic chromosome axes are hubs for regulated proteolysis via SUMO-dependent control of the ubiquitin-proteasome system