Atypical neuroleptic malignant syndrome. “Doing more harm than gain”

Neuroleptic malignant syndrome (NMS) a rare, idiosyncratic, and potentially fatal adverse reaction can be deceptive especially when the hallmark features are lacking. Most diagnostic criteria include fever and muscle rigidity, although NMS may present without either. Delirium, agitation and catatonia can be the earliest features of NMS and in acute care settings, concomitant use of sedatives and anti-psychotics by the attending clinicians may even obscure the sentinel signs of NMS and further aggravate the underlying insult. A strong clinical suspicion based on clinical history is crucial for early diagnosis and treatment and the strict adherence to the classical criteria of NMS may lead to a diagnostic delay and dire consequences for these patients and sometimes this delay can procure death

Whole exome screening identifies novel and recurrent WISP3 mutations causing progressive pseudorheumatoid dysplasia in Jammu and Kashmir-India

We report identification and genetic characterization of a rare skeletal disorder that remained unidentified for decades in a village of Jammu and Kashmir, India. The population residing in this region is highly consanguineous and a lack of understanding of the disorder has hindered clinical management and genetic counseling for the many affected individuals in the region. We collected familial information and identified two large extended multiplex pedigrees displaying apparent autosomal recessive inheritance of an uncharacterized skeletal dysplasia. Whole exome sequencing (WES) in members of one pedigree revealed a rare mutation in WISP3:c.156C > A (NP-003871.1:p.Cys52Ter), that perfectly segregated with the disease in the family. To our surprise, Sanger sequencing the WISP3 gene in the second family identified a distinct, novel splice site mutation c.643+1G > A, that perfectly segregated with the disease. Combining our next generation sequencing data with careful clinical documentation (familial histories, genetic data, clinical and radiological findings), we have diagnosed the families with Progressive Pseudorheumatoid Dysplasia (PPD). Our results underscore the utility of WES in arriving at definitive diagnoses for rare skeletal dysplasias. This genetic characterization will aid in genetic counseling and management, critically required to curb this rare disorder in the families

“Toxic” beef bone soup

Hypercalcaemia is most commonly caused by primary hyperparathyroidism or malignancy. Vitamin D intoxication, also a cause of hypercalcaemia, is mostly caused by excessive administration of vitamin D-containing medications and excessive intake of foods fortified with vitamin D. We present a young cricketer, with recurrent vomiting due to hypercalcaemia and hypervitaminosis D, who used to drink large volumes of soup prepared by boiling long beef bones, for many months. This case presentation highlights the importance of in-depth dietary history for arriving at proper diagnosis

Tuberculosis masquerading as polymyalgia rheumatica

Polymyalgia rheumatica (PMR) is a connective tissue disorder of unknown aetiology. It is hypothesized that, in a genetically predisposed person, its pathogenesis is triggered by an environmental factor, possibly a hitherto unknown infectious agent. We present the case of a 68-year-old woman who is being treated for PMR. She developed tubercular lymphadenitis and erythema nodosum and improved with antitubercular treatment. We hypothesize that the trigger for pathogenesis of PMR in this lady was antigen of Mycobacterium tuberculosis

Double osteomalacia

35-year old woman presented, with chronic vague ill health, subacute symptoms of decreased appetite, increased thirst, excessive urination, and rib pains, and acute quadriparesis. On evaluation, she was found to have type 1 Renal tubular acidosis, pseudofractures of ribs and Hypovitaminosis D. Administration of oral solution containing potassium citrate and citric acid along with pharmacological doses of Vitamin D and supportive treatment improved her condition remarkably. This case report highlights interesting coexistence of two disorders, one very common (Hypovitaminosis D) and one rare (Distal Renal Tubular Acidosis dRTA), in same patient, producing same pathology (osteomalacia

Fever of unknown origin - Hidden in the head

The original algorithmic approach, as outlined by de Kleijn and colleagues and practiced commonly, envisages performing computed tomography (CT) of chest, abdomen, and pelvis in patients with classical fever of unknown origin (FUO), in whom no potentially diagnostic clue exists. It further envisages performing positron emission tomography (PET) scan, if CT scan is unrevealing. Imaging of head and neck especially magnetic resonance imaging (MRI) has not been included in this algorithm, that leaves these important regions unexplored in most settings where PET scan is unavailable. MRI is a safe modality for evaluating central nervous system lesions and its role in FUO has not been adequately evaluated. We present three patients of FUO in whom the diagnosis of tuberculoma of brain as a cause of prolonged pyrexia got delayed because the MRI of head was not done initially, to comply with the approach of minimum diagnostic evaluation

“Peripheral Neuropathy Crippling Bronchial Asthma”: Two Rare Case Reports of Churg-Strauss Syndrome

Churg-Strauss syndrome (CSS) is a rare cause of vasculitic neuropathy. Although rare and potentially fatal, Churg-Strauss syndrome (CSS) is easily diagnosable and treatable. The presence of bronchial asthma with peripheral neuropathy in a patient alerts a physician to this diagnosis. This is vividly illustrated by the presented two cases who had neuropathy associated with bronchial asthma, eosinophilia, sinusitis, and positive perinuclear antineutrophil cytoplasmic antibodies (p-ANCA) test, which improved with administration of steroids

Geographic Isolation and Endogamous Practices Provide Higher Risk of Genetic Disorders in Jammu and Kashmir

Rare disorders are poorly understood, most often remain uncharacterized or patients are misdiagnosed due to lack of specific clinical resources. Understanding the basics of inheritance is essential in such cases as it helps to figure out the plausibility of a disorder as an inherited or genetic disease. Though identification and characterization of such disorders is complicated, Next generation Sequencing has come up as a tool in recent times and is of great help. It is quite visible in literature that since the advent of this methodology, a drastic increase in identification and genetic characterization of various rare diseases across the world has occurred. We emphasize on NGS/WES, as an effective method in understanding uncharacterized Mendelian Disorders. It is of great help, especially in developing countries and regions like Jammu and Kashmir where, such familial disorders exist in abundance, due to very high consanguinity, but remain undiagnosed/misdiagnosed due to lack of specialized testing. We have collected huge number of highly extended families representing various rare genetic disorders and trying to elucidate the genetic cause and biology of the diseases in these families

“Excess gooD can be Dangerous”. A case series of iatrogenic symptomatic hypercalcemia due to hypervitaminosis D

Vitamin D is increasingly recognized to have several beneficial effects. Its toxicity, causing hypercalcemia, is considered as extremely rare. We report case series of 15 patients (most of them being elderly subjects) with iatrogenic symptomatic hypercalcemia in whom toxicity occurred due to empirical excessive administration of vitamin D by oral and parenteral rout