A founder RAB27A variant causes Griscelli syndrome type 2 with phenotypic heterogeneity in Qatari families.

Griscelli syndrome type 2 (GS2) is a rare autosomal recessive disorder caused by pathogenic variants in the RAB27A gene and characterized by partial albinism, immunodeficiency, and occasional hematological and neurological involvement. We reviewed and analyzed the medical records of 12 individuals with GS2 from six families belonging to a highly consanguineous Qatari tribe and with a recurrent pathogenic variant in the RAB27A gene (NM_004580.4: c.244C > T, p.Arg82Cys). Detailed demographic, clinical, and molecular data were collected. Cutaneous manifestations were the most common presentation (42%), followed by neurological abnormalities (33%) and immunodeficiency (25%). The most severe manifestation was HLH (33%). Among the 12 patients, three patients (25%) underwent HSCT, and four (33%) died. The cause of death in all four patients was deemed HLH, providing evidence for this complication's fatal nature. Interestingly, two affected patients (16%) were asymptomatic. This report highlights the broad spectrum of clinical presentations of GS2 associated with a founder variant in the RAB27A gene (c.244C > T, p.Arg82Cys). Early suspicion of GS2 among Qatari patients with cutaneous manifestations, neurological findings, immunodeficiency, and HLH would shorten the diagnostic odyssey, guide early and appropriate treatment, and prevent fatal outcomes.

In patients with chronic heart failure which polypharmacy pheno-groups are associated with adverse health outcomes? (Polypharmacy pheno-groups and heart failure outcomes).

BACKGROUND: Patients with heart failure are living longer with the inevitable morbidity of rising medication counts. It remains uncertain what fraction of this ensuing polypharmacy exactly predicts adverse clinical outcomes. METHODS: This prospective study examined records of patients admitted to a Weill Cornell-affiliated tertiary medical institution with a confirmed diagnosis of heart failure between January 2018 to January 2022. Each patient's medications for the past four months were tallied, and a definitional threshold of ≤4, ≥5, ≥10 medications was established. The primary outcome was all-cause mortality within the study period. RESULTS: Out of a total of 7354 patients included in the study, 70 % were males with a median age of 59 years IQR (48-71). The median (IQR) age-adjusted Charlson Comorbidity Index (CCI) was 21-5. A total of 1475 (20 %) participants died within the study period. Patient cohorts with excessive polypharmacy (≥9 medications) had the highest probability of survival up to 1.6 years compared to those with lower medication thresholds (≤4); the mortality rate decreased by 18 % for patients with excessive polypharmacy [HR = 0.82, 95 % CI: 0.71-0.94]). Conversely, patients with non-heart failure-related polypharmacy had increased risks of ICU admissions (aOR = 1.78, 95 % CI: 1.13-2.70). CONCLUSION: In an examination of a database of patients with chronic heart failure, major non-heart failure-related polypharmacy was associated with increased risks in intensive care admissions. Excessive polypharmacy was associated with increased rates of survival.

Myxedema Psychosis: Neuropsychiatric Manifestations and Rhabdomyolysis Unmasking Hypothyroidism.

Background. Hypothyroidism is a prevalent endocrine disorder, often presenting with a spectrum of symptoms reflecting a hypothyroid state. It is also generally linked to causing mood swings, psychomotor slowing, and fatigue; however, in rare instances, it may lead to or induce acute psychosis, a condition referred to as myxedema psychosis (MP). We report a case of myxedema psychosis and present a literature review discussing its presentation, diagnosis, management, and prognosis. Case Presentation. A 36-year-old lady presented with one-week history of persecutory and paranoid delusions, along with visual and auditory hallucinations. She had no prior history of psychiatric illnesses. She underwent total thyroidectomy three years before the current presentation due to papillary thyroid cancer. She was not on regular follow-up, nor any specific therapy. On examination, she was agitated and violent. There were no signs of myxedema, and the physical exam was unremarkable. The initial workup showed a mild elevation in serum creatinine. Additional investigations revealed a high thyroid-stimulating hormone (TSH) of 56.6 mIU/L, low free T4 < 0.5 pmol/L, elevated creatine kinase of 3601 U/L, and urine dipstick positive for blood, suggestive of myoglobinuria. MRI of the head was unremarkable. We diagnosed her as a case of myxedema psychosis and mild rhabdomyolysis. She was started on oral thyroxine 100 mcg/day, fluoxetine 20 mg daily, and as-needed haloperidol. She was closely followed and later transferred to the Psychiatry Hospital for further management. Within one week, her symptoms improved completely, and she was discharged off antipsychotics with additional scheduled follow-ups to monitor TFTs and observe for any recurrence. Discussion and Conclusion. Myxedema psychosis is a rare presentation of hypothyroidism-a common endocrine disorder. Scarce data are describing this entity; hence, there is currently a lack of awareness amongst clinicians regarding proper identification and management. Moreover, the atypical nature of presentations occasionally adds to a diagnostic dilemma. Thus, any patient with new-onset psychosis should be screened for hypothyroidism, and awareness of this entity must be emphasized amongst clinicians and guideline makers.

The Unusual Late-Onset Graves' Disease following Hashimoto's Related Hypothyroidism: A Case Report and Literature Review.

Background. The shift of Graves' disease (GD) to Hashimoto's disease- (HD-) related hypothyroidism is well established. However, the opposite is rare. This is likely to the loss of critical thyroid mass available for stimulation by thyroid hormone receptor stimulating antibody, making this shift unusual. Herein, we report a young lady with a late shift from HD into GD and present a scoping literature review. Case presentation. We report a twenty-five-year-old lady with a sixteen-year-history of Hashimoto's-related hypothyroidism stable on levothyroxine. While following in the clinic, she started developing thyrotoxic symptoms in the form of anxiety, weight loss, and palpitation. Physical examination was remarkable for mild exophthalmos. The thyroid function test confirmed hyperthyroidism. Levothyroxine-induced hyperthyroidism was initially suspected; however, the symptoms did not improve despite reducing and stopping levothyroxine. Subsequent workup confirmed the diagnosis of GD. Discussion and Conclusion. This case highlights a unique association that has significant diagnostic and management implications. This shift should be considered when hyperthyroidism persists despite reducing or stopping levothyroxine. The diagnosis is made utilizing antibody titers and radioiodine update scan. While the management depends on the disease's stage and the treating physician preference, antithyroid agents can be used initially. Following up these patients is essential as the shift can be transient.

Acute Confusional Migraine: Unusual Great Masquerader-Case Report and Literature Review.

Background. Acute confusional migraine (ACM) is a rare variant of migraine, mainly prevalent in children and adolescents. It is not currently indexed as a distinct variant of migraine likely since only a few cases were reported in the adult population. We report a case of delayed ACM diagnosis in a young man and present a concise-related literature review. Case Presentation. A thirty-eight-year-old man with a past medical history of migraine, not on any treatment, presented with headaches accompanied by confusion. Over a two-year period before the current presentation, he experienced two episodes of confusion, which required hospital admission for evaluation: once mislabeled as a psychiatric illness and diagnosed as a migrainous infarct in the second hospitalization. In the current presentation, he reported a similar history of headache accompanied by confusion. The examination was remarkable for disorientation; otherwise, no focal deficit was elicited. Laboratory testing, cerebrospinal fluid, and neurological imaging were all unremarkable. His symptoms improved spontaneously within less than twenty-four hours, similar to his previous presentations. After two-year history of episodic confusion and after excluding other plausible causes of confusion, guided by proposed diagnostic criteria, we diagnosed him as a case of ACM. The patient remains well at the follow-up of two months after discharge. Discussion and Conclusion. ACM is a rare variant of migraine and is often a challenge for clinicians to diagnose appropriately. Until recent years, the disease was thought to be limited to children and adolescents. However, recently few reports also expanded the incidence of this entity to the adult population. There is a significant gap in knowledge about proper identification and treatment of this condition, leading to delayed or overlooked ACM diagnosis. Moreover, the recent edition of the International Classification of Headache Disorders (ICHD-3) does not account for this entity, thereby further adding to physicians' lack of awareness regarding this migraine subtype. The authors emphasize that clinicians be aware of this entity and adequately utilize the existing proposed diagnostic criteria for ACM until standardized and validated tools are available. We also believe that this entity should be acknowledged in the subsequent migraine guidelines and classifications.

Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids, with Cranial and Caudal Extension.

A 23-year-old lady presented with vertigo and imbalance in walking, blurring of vision, diplopia, and headache, in addition to numbness in the lower limbs over a period of six days. On examination patient had nystagmus, ataxia, positive Romberg test, and hyperreflexia. MRI examination of the brain and spinal cord showed evidence of faint bright signal intensity foci in T2/FLAIR involving bilateral cerebral hemispheres, subcortical deep white matter, bilateral thalami, posterior pons and left brachium pontis, and basal ganglia, with small nodular enhancement that aligned along curvilinear structures; those lesions also were apparent along the spinal cord at multiple levels. The clinical and radiological features suggested CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) syndrome. Symptoms improved dramatically with high dose oral corticosteroids. Our report addresses the radiological and clinical pattern of a case of CLIPPERS rhombencephalitis, with added superior and inferior extension to involve the brain and spinal cord, which is to emphasize the importance of raising the awareness of this disease and the combined role of radiologist and physicians for the diagnosis of this potentially treatable entity, responsive to glucocorticosteroid immunosuppression.