A Patient With Pelizaeus-Merzbacher Disease Caused by a c.67G>A Mutation in the PLP1 Gene.

Pelizaeus-Merzbacher disease is a tremendously rare genetic disorder caused by a mutation on the X chromosome. The mutation affects a gene critical to white matter myelination and results in significant neurological issues. Here, we present one such case of a child diagnosed with Pelizaeus-Merzbacher disease. A relatively normal gestation and birth belied the underlying issue until he presented to the emergency department a month after birth with seizure-like activity and failure to thrive. After intensive evaluation and treatment, the patient was diagnosed with the illness and received surgery to place a tracheostomy and a gastrostomy tube to treat the stridor and failure to thrive caused by his illness. After approximately a month and a half of inpatient treatment, the patient was able to be discharged home in stable condition.

Rheumatoid Arthritis-Linked Artificial Joint Infections Leading to Amputations.

Rheumatoid arthritis (RA) is a common autoimmune condition that can rarely cause more serious complications, such as permanent joint damage or infection, and may pose a significant additional risk during certain routine procedures. One major consequence of RA is that it can lead to serious and permanent joint damage requiring arthroplasty. Additionally, RA is a known cause of infection, with orthopedic prosthetic joint infections (PJIs) being documented. We explore one such serious case of a patient with long-term RA and a left knee joint replacement who presented to the emergency room with a serious PJI. History revealed that he repeatedly was affected by infections and had an extensive and severe clinical course, including nine revision surgeries. After a physical examination, imaging was performed, which further supported the diagnosis of joint infection. Considering the extensive number of attempts to salvage the joint, clinicians decided an above-knee amputation was necessary. This case highlights the fact that RA both increases the need for orthopedic arthroplasties and the risk of complications from these procedures, complicating clinical decision-making for physicians. Additionally, this patient had other underlying medical conditions and social habits that may have contributed to his severe clinical course, and we hope to explore these, discuss possible methods of modifying them, and assist clinicians in not only better treating similar patients but also emphasizing the importance of further developing standardized predictive algorithms and scoring tools.

Phenazopyridine-Induced Methemoglobinemia: A Case Report.

Methemoglobinemia is a condition caused by increased methemoglobin, a reduced form of hemoglobin, in the blood. This causes the molecules to bind oxygen more tightly and decreases their ability to release that oxygen to tissue. Most cases of methemoglobinemia are acquired and occur either in pediatric populations or in individuals with predisposing conditions. This report illustrates a case of an otherwise healthy 31-year-old patient presenting to the emergency department with cyanosis of the hands and mouth and an O2 saturation of 78% after taking increased doses of the over-the-counter medication phenazopyridine. A "chocolate-brown" color of her arterial blood, and increased methemoglobin levels of 20.2%, confirmed the diagnosis of methemoglobinemia. She was treated with both methylene blue and ascorbic acid, and her oxygen saturation and serum chemistry returned to normal levels within a few hours. The case highlights the importance of discussing the dosage of all over-the-counter medications with patients and recognizing the signs and symptoms of methemoglobinemia.

Necrotizing Fasciitis Presenting as Generalized Weakness, Malaise, and Acute Kidney Injury.

Necrotizing fasciitis (NF) is a surgical emergency that must be diagnosed promptly in order to avoid serious consequences or death. Additionally, symptoms of this condition are similar to less severe skin and soft tissue infections such as cellulitis or erysipelas and can be easily confused. In this case, the patient presented to the emergency department with systemic symptoms, notably malaise and generalized weakness. A cutaneous complaint, a "labial cyst", was only elicited after more specific questioning. Laboratory investigations revealed abnormal renal function tests (RFTs), suggestive of an acute kidney injury. An abdominal/pelvic computed tomography (CT) showed gas in the subcutaneous tissue. These findings led to clinical suspicion of NF, prompting a general surgery consultation. The surgeon proceeded to perform extensive debridement following the discovery of necrotic tissue. The prompt diagnosis and treatment of this condition resulted in patient survival and expected recovery. It is, therefore, critical to keep this condition in mind when diagnosing apparent skin and soft tissue infections presenting with abnormal RFTs due to the possibility of rapid decline and death if the NF is left untreated. Additionally, this is a case of less frequent Fournier's gangrene in a non-diabetic female. Finally, it underlines the importance of eliciting additional symptoms, even those that may seem unrelated, or less concerning, to the patient's initial complaint.

Spider Bite-Induced Facial Nerve Palsy.

Spider bites, while rarely confirmed beyond a doubt, should always be in the differential for any severe symptoms or infection out of proportion to presentation with the suspected presence of appropriate vectors. While most arthropod bites will only result in mild localized irritation, the potential to cause severe cutaneous and systemic effects should not be overlooked. We present one such case, in which a presumed brown recluse (Loxosceles reclusa) bite on the neck resulted in severe illness with systemic manifestations. The patient presented to the emergency room minimally responsive with left-sided facial nerve palsy and septic shock. While the admitting physician initially prioritized stabilizing the patient, he noted the left-sided cervical cellulitis. Thorough history taking revealed that the patient had been worsening since being bitten by a spider three days prior to admission. After a month-long hospital stay and multidisciplinary treatment, the patient was transferred to a larger center with facial paralysis still present.

CRISPR/Cas9 interrogation of the mouse Pcdhg gene cluster reveals a crucial isoform-specific role for Pcdhgc4.

The mammalian Pcdhg gene cluster encodes a family of 22 cell adhesion molecules, the gamma-Protocadherins (γ-Pcdhs), critical for neuronal survival and neural circuit formation. The extent to which isoform diversity-a γ-Pcdh hallmark-is required for their functions remains unclear. We used a CRISPR/Cas9 approach to reduce isoform diversity, targeting each Pcdhg variable exon with pooled sgRNAs to generate an allelic series of 26 mouse lines with 1 to 21 isoforms disrupted via discrete indels at guide sites and/or larger deletions/rearrangements. Analysis of 5 mutant lines indicates that postnatal viability and neuronal survival do not require isoform diversity. Surprisingly, given reports that it might not independently engage in trans-interactions, we find that γC4, encoded by Pcdhgc4, is the only critical isoform. Because the human orthologue is the only PCDHG gene constrained in humans, our results indicate a conserved γC4 function that likely involves distinct molecular mechanisms.