Ashu Rastogi

Novel **SOST** gene mutation in a sclerosteosis patient and her parents

INTRODUCTION Sclerosteosis (OMIM 269500) is a rare autosomal recessive condition characterized by increased bone density associated with syndactyly. It is linked to a genetic defect in the SOST gene coding for sclerostin. So far, six different loss-of-function mutations in SOST have been reported in patients with sclerosteosis. Our objective was to sequence and identify mutation in the SOST and LRP5 genes which are known to be causal for craniotubular hyperostosis in a patient from India. PATIENT AND METHODS A 22year old woman presented with typical features of sclerosteosis in form of progressive visual and hearing loss, syndactyly and radiographs revealing increased density of bone. Genomic sequencing of the SOST gene as well as exons 2, 3 and 4 of the LRP5 gene was performed. RESULTS We identified a novel homozygous mutation in the (SOST) gene, characterized as one nucleotide insertion resulting in a frame shift mutation and loss of functional sclerostin. Her parents were also found to have a similar but heterozygous mutation in the (SOST) gene. CONCLUSION A novel frame shift mutation in the (SOST) gene causing loss of functional sclerostin was identified in a patient with sclerosteosis and her parents.

Celiac disease: A missed cause of metabolic bone disease.

Introduction: Celiac disease (CD) is a highly prevalent autoimmune disease. The symptoms of CD are varied and atypical, with many patients having no gastrointestinal symptoms. Metabolic bone disease (MBD) is a less recognized manifestation of CD associated with spectrum of musculoskeletal signs and symptoms, viz. bone pains, proximal muscle weakness, osteopenia, osteoporosis, and fracture. We here report five patients who presented with severe MBD as the only manifestation of CD. Materials and Methods: Records of 825 patients of CD diagnosed during 2002–2010 were retrospectively analyzed for clinical features, risk factors, signs, biochemical, and radiological parameters. Results: We were able to identify five patients (0.6%) of CD who had monosymptomatic presentation with musculoskeletal symptoms and signs in the form of bone pains, proximal myopathy, and fragility fractures without any gastrointestinal manifestation. All the five patients had severe MBD in the form of osteopenia, osteoporosis, and fragility fractures. Four of the five patients had additional risk factors such as antiepileptic drugs, chronic alcohol consumption, malnutrition, and associated vitamin D deficiency which might have contributed to the severity of MBD. Conclusion: Severe metabolic disease as the only presentation of CD is rare. Patients show significant improvement in clinical, biochemical, and radiological parameters with gluten-free diet, calcium, and vitamin D supplementation. CD should be looked for routinely in patients presenting with unexplained MBD.

An unusual presentation of a usual disorder: Van Wyk-Grumbach syndrome

Van Wyk-Grumbach syndrome (VWGS) is characterized by juvenile hypothyroidism, delayed bone age, and isosexual precocious puberty. A 10.7-year-old girl presented with premature menarche and isosexual precocity. She had delayed bone age and multicystic ovaries. High circulating levels of TSH with prepubertal LH confirmed the diagnosis of VWGS. Tendency to manifest sexual precocity in VWGS may be directly related to the severity of the TSH elevation. High circulating levels of TSH acting directly on FSH receptors are the actual mediators of precocity.

Recurrent diabetic myonecrosis: a rare complication of a common disease.

Spontaneous aseptic diabetic muscle infarction (DMI) is one of the rare complications of diabetes. We report a case of type 2 diabetes mellitus with advanced microvascular complications presenting with severe muscular pain. She was diagnosed as DMI on the basis of clinical presentation, radiological and histopathological investigations. She was managed conservatively. During 18 months of follow up, she had good improvement but subsequently other muscle groups were involved suggesting recurrent DMI.

Recurrent thyroid nodule: spindle epithelial tumor with thymus like differentiation (SETTLE).

Thyroid nodules are uncommon in childhood and recurrent thyroid nodules even rarer. Spindle epithelial tumor with thymus-like differentiation (SETTLE), a rare and distinctive lowgrade neoplasm is amongst the differential diagnosis of solitary thyroid nodule in children. We describe a boy who underwent completion thyroidectomy for SETTLE in the thyroid remnant four years after initial lobectomy was performed for the same diagnosis. Patients with SETTLE are to be closely followed as multifocality may manifest and be detected later.

The microbiology of diabetic foot infections in patients recently treated with antibiotic therapy: A prospective study from India

AIM Clinicians often treat clinically infected diabetic foot ulcers without information from cultures of the wound. The results of wound cultures may also be affected by previous antibiotic therapy. Thus, we aimed to study the microbial isolates, and antimicrobial sensitivity of previously treated patients with a clinically infected DFU. RESEARCH DESIGN AND METHODS 293 consecutive patients with clinically infected DFU on prior antimicrobial treatment within the immediate past few days for a duration greater than one week were evaluated for microbial etiology, antibiotic sensitivity and final outcomes. Appropriate tissue samples i.e. purulent drainage, soft-tissue and/ or bone were obtained for aerobic/anaerobic cultures and antimicrobial sensitivities. 71 patients with missing prior antibiotic data were excluded. RESULTS 313 tissue samples obtained from 222 patients isolated 317 causative organisms. Most of the culture results from tissue specimens were mono-microbial (93.2%) compared to 37% in our previous cohort of 60 patients. Pseudomonas aeruginosa was the most common organism isolated on culture of bone (26.9%) or soft tissue (23.2%) specimen, respectively. Only 23% and 64% of P. aeruginosa isolates and 5.6% and 44% of Acinetobacter sp. were sensitive to quinolones and cephalosporins, respectively. CONCLUSIONS Clinically infected DFU recently treated with antibiotics have predominant monomicrobial and multi drug-resistant infection. Quinolones as an empirical antibiotic choice may not be appropriate in this setting.

Osteonecrosis of jaw associated with bisphosphonate use

Bisphosphonates are associated with osteonecrosis of the jaw (ONJ) that is defined as an area of exposed, nonvital bone in the maxilla or mandible persisting over 6–8 weeks. We describe a case of 55-year-old female who developed ONJ after tooth extraction and had been receiving oral ibandronate for osteoporosis. Diagnosis of ONJ was confirmed on CT scan. The patient was managed conservatively as she denied teriparatide therapy because of cost constraints.

Comparative study of clinical features of patients with celiac disease & those with concurrent celiac disease & type 1 diabetes mellitus

Background & objectives: Celiac disease (CD) and type 1 diabetes mellitus (T1DM) share a common genetic locus and clinical manifestations. The present study was planned to compare clinical, biochemical and hormonal profiles of patients with CD and CD with T1DM. Methods: Records of CD patients with age ≤20 yr, available anthropometric measurements, haematological, biochemical and hormonal workup with tissue transglutaminase IgA antibody and duodenal biopsy (Marsh grade) were screened. The patients were divided into two groups i.e., CD alone (Group A) and concurrent CD with T1DM (Group B). Results: One hundred and nine patients of CD (57 male) with a mean age of 14.9±2.9 yr were evaluated. Of these, 86 (78.9%) patients had CD alone and 23 (13 females) (21.1%) patients had CD with T1DM. The age at diagnosis and the lag duration for the diagnosis of CD were 11.5±4.6 versus 13.8±3.4 yr (P<0.05) and 48.8 ±43.3 versus 20.2±31.8 months (P<0.05) in groups A and B, respectively. The most common histopathological grade was type 3b (59.2%) in group A and type 2 (42.1%) in group B. Short stature (87% vs. 40.9%; P<0.01), anaemia (80.9% vs. 45%, P<0.01) and delayed puberty (61.9% vs. 29.4%; P<0.01) were more common in group A. Interpretation & conclusions: Patients with CD alone have a longer lag time to diagnosis and consequent sequel in the form of anaemia, short stature and delayed puberty, as compared to patients with concurrent CD and T1DM.

A comparison between intensive and conventional cabergoline treatment of newly diagnosed patients with macroprolactinoma

Intensive treatment with cabergoline may lead to earlier reduction in prolactin and tumour volume in comparison to conventional schedule.

Herlyn- werner- wunderlich syndrome: A rare urogenital anomaly masquerading as acute abdomen

A 14-yr-old girl presented with chief complaint of lower abdominal pain during menses for last 1 year. Her menstrual history suggested no abnormality except dysmenorrhea. On examination secondary sexual characters were normal for age. Per abdomen examination and rest of the systemic examination was also normal. A provisional diagnosis of primary dysmenorrhea was made and the patient counseled accordingly. She was advised to take anti-spasmodic drugs during her menstrual periods and follow up monthly.