DICER1 Syndrome in Twins With Ovarian Sertoli-Leydig Cell Tumor and Papillary Thyroid Carcinoma.

DICER1 syndrome is a rare autosomal dominant syndrome resulting in benign and malignant tumors in various organs with tumors in endocrine organs (pituitary, thyroid, adrenal, ovaries, and pancreas). Here we present a rare case of 18-year-old twin sisters with DICER1 syndrome who presented at the age of 15 years with hirsutism, deepening of the voice, and amenorrhea. They were diagnosed with a Sertoli-Leydig cell tumor of the ovary and underwent unilateral oophorectomy, with no evidence of recurrence or metastasis during follow-up. Genetic analysis showed the same germline DICER1 mutation in both cases. They also had large multinodular goiters (nodule size ranging from 1.0 to 2.3 cm) nodules were increasing in size. Fine needle aspiration cytology (FNAC) of thyroid nodules for both the sisters showed atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), and they both underwent total thyroidectomy revealing papillary thyroid carcinoma. No pituitary lesion was observed in the brain magnetic resonance imaging (MRI) of either of them. A chest CT scan showed bilateral sub-pleural benign-looking nodules in both patients. The twin sisters developed some features, such as Sertoli-Leydig cell tumor, multinodular goiter, and papillary thyroid carcinoma, and had positive genetic tests for DICER1 germline mutation. The father and paternal grandfather had a family history of papillary thyroid carcinoma. Both patients require active surveillance due to the increased risk of developing tumors in multiple organs associated with this disease.

Higher carbohydrate intake in relation to non-alcoholic fatty liver disease in patients with type 2 diabetes.

Background: Non-alcoholic fatty liver disease (NAFLD) is an overlooked complication of type 2 diabetes (T2D). Current recommendations for the management of NAFLD are mainly focused on weight reduction, overlooking the role of macronutrient composition. Although dietary carbohydrates play a major role in intrahepatic fat synthesis, their association with the progression of liver steatosis has not been fully investigated in patients with T2D. Aim: To investigate the association between higher carbohydrate intake and the presence of liver steatosis in patients with T2D. Methods: This cross-sectional study included men and women aged 18-60 years diagnosed with T2D. Anthropometric measurements, hepatic steatosis assessment using the controlled attenuation parameter (CAP), blood samples, and dietary data were analyzed. Participants were divided into two groups: NAFLD and NAFLD-free. A two-sample t-test was used to evaluate the differences between the two groups. Stepwise multiple linear regression models adjusted for potential confounders were used to determine the association between CAP values and higher carbohydrate intake. Results: In total, 358 participants were included. NAFLD was present in 79.3% of the participants. Body mass index, waist circumference, ALT, HbA1c, and triglycerides showed direct, while HDL-Cholesterol revealed inverse associations with CAP values. No significant relationship was found between carbohydrate intake and steatosis in the total study sample; however, multiple linear regression analysis revealed a significant relationship between carbohydrate intake and CAP values in patients aged ≤50 years. Conclusion: In patients with T2D, higher carbohydrate intake was associated with liver steatosis in those aged 50 years and below. Further studies are required to confirm the causality between carbohydrate intake and liver steatosis.

Transient elastography for the prevalence of non-alcoholic fatty liver disease in patients with type 2 diabetes: Evidence from the CORDIAL cohort study.

Background: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in patients with type 2 diabetes mellitus (T2DM). This study aimed to investigate the prevalence of NAFLD among Saudi patients with T2DM using transient elastography. Methods: A total of 490 patients with T2DM who attended diabetes and primary care clinics were recruited. Controlled attenuation parameter (CAP) and liver stiffness measurements (LSM) were obtained via FibroScan to assess steatosis and fibrosis. Results: Of the examined 490 patients with T2DM, 396 (80.8%) had hepatic steatosis (CAP ≥248 dB/m): 326 (66.5%) had severe steatosis (CAP ≥280 dB/m), while 41 (8.4%) and 29 (5.9%) had mild (CAP ≥248 to <268 dB/m) and moderate steatosis (CAP ≥268 to <280 dB/m), respectively. Of the 396 patients with steatosis, only 35 (8.8%) had LSM ≥7.9 kPa, suggesting the presence of fibrosis, while 361 (91%) had LSM <7.9 kPa, indicating the absence of fibrosis. Increased body mass index (BMI), waist circumference, systolic blood pressure (SBP), and alanine aminotransferase (ALT) were positively associated with both steatosis and fibrosis. After adjusting for age and gender, data from logistic regression analysis demonstrated BMI, waist circumference, SBP, ALT, and high-density lipoprotein (HDL) as significant independent factors for steatosis, while SBP was the only significant predictor associated with fibrosis. Conclusions: Our results demonstrate an increase in prevalence of NAFLD in Saudi patients with T2DM, based on transient elastography and CAP score. The risk of NAFLD appears to be higher in T2DM patients with abdominal obesity, elevated SBP, and increased ALT levels, which supports the screening of these conditions in patients with T2DM.

Three Siblings With Woodhouse-Sakati Syndrome: A Case Report of A New Saudi Family.

Woodhouse-Sakati syndrome (WSS) is a rare autosomal recessive multi-system genetic disease caused by loss of function mutations in the DCAF17 gene on chromosome 2q31.1. The disease is characterized by gradual neurologic degeneration and polyendocrinopathy, particularly noteworthy for hypogonadism, beginning in early adolescence. Clinical features show wide variability with no clear genotype-phenotype correlation. The pathophysiology of WSS is unclear at present and no specific treatment is available other than hormone replacement which is administered in the course of individualized symptomatic multidisciplinary care. Genetic testing helps in confirming the diagnosis along with genetic counseling of the patient and family members. Here we report multiple cases of WSS in three siblings from a new Saudi Arabia family who were diagnosed with WSS as a consequence of a common founder mutation in the DCAF17 gene with DNA analysis showing a homozygous single nucleotide frameshift deletion (c.436delC) in exon 4 of the gene.

A Case of Fluorosis: Fluoride-Induced Osteopetrosis.

There are multiple etiologies of increased bone density, including osteopetrosis and fluorosis. Osteopetrosis can either be a malignant autosomal recessive condition found in children or a benign autosomal dominant adult variant; both of which are characterized by decreased bone resorption. In contrast, fluorosis is characterized by increased bone formation secondary to chronic fluoride intoxication, but with a similar clinical manifestations to osteopetrosis. A 70-year-old lady with generalized joint aches, stiffness as well as fatigue, was found to have high bone mineral density and alarmingly high fluoride levels. The patient was found to be drinking fluoride containing water from an untreated local well for many years. Fluorosis results in increased bone mineral density and disease progression correlates with length of exposure. Fluorosis can result in reversible musculocutaneous symptoms and radiological findings. However, severe chronic cases may develop irreversible neurologic manifestations. Urinary fluoride testing is the screening modality of choice, and the key component of management is avoidance of the source of fluoride intoxication as well as monitoring of urinary fluoride levels.

Association of HLA-DR-DQ alleles, haplotypes, and diplotypes with type 1 diabetes in Saudis.

AIMS: Type 1 diabetes (T1D) is an autoimmune disease that affects many children worldwide. Genetic factors and environmental triggers play crucial interacting roles in the aetiology. This study aimed to assess the contribution of HLA-DRB1-DQA1-DQB1 alleles, haplotypes, and genotypes to the risk of T1D among Saudis. METHODS: A total of 222 children with T1D and 342 controls were genotyped for HLA-DRB1, -DQA1, and -DQB1 using reverse sequence-specific oligonucleotide (rSSO) Lab Type high definition (HD) kits. Alleles, haplotypes, and diplotypes were compared between cases and controls using the SAS statistical package. RESULTS: DRB1*03:01-DQA1*05:01-DQB1*02:01 (32.4%; OR = 3.68; Pc < .0001), DRB1*04:05-DQA1*03:02-DQB1*03:02 (6.6%; OR = 6.76; Pc < .0001), DRB1*04:02-DQA1*03:01-DQB1*03:02 (6.0%; OR = 3.10; Pc = .0194), DRB1*04:01-DQA1*03:01-DQB1*03:02 (3.7%; OR = 4.22; Pc = .0335), and DRB1*04:05-DQA1*03:02-DQB1*02:02 (2.7%; OR = 6.31; Pc = .0326) haplotypes were significantly increased in cases compared to controls, whereas DRB1*07:01-DQA1*02:01-DQB1*02:02 (OR = 0.41; Pc = .0001), DRB1*13:01-DQA1*01:03-DQB1*06:03 (OR = 0.05; Pc < .0001), DRB1*15:01-DQA1*01:02-DQB1*06:02 (OR = 0.03; Pc < .0001), and DRB1*11:01-DQA1*05:05-DQB1*03:01 (OR = 0.07; Pc = .0291) were significantly decreased. Homozygous DRB1*03:01-DQA1*05:01-DQB1*02:01 genotypes and combinations of DRB1*03:01-DQA1*05:01-DQB1*02:01 with DRB1*04:05-DQA1*03:02-DQB1*03:02, DRB1*04:02-DQA1*03:01-DQB1*03:02, and DRB1*04:01-DQA1*03:01-DQB1*03:02 were significantly increased in cases than controls. Combinations of DRB1*03:01-DQA1*05:01-DQB1*02:01 with DRB1*07:01-DQA1*02:01-DQB1*02:02 and DRB1*13:02-DQA1*01:02-DQB1*06:04 showed low OR values but did not remain significantly decreased after Bonferroni correction. CONCLUSIONS: HLA-DRB1-DQA1-DQB1 alleles, haplotypes, and diplotypes in Saudis with T1D are not markedly different from those observed in Western and Middle-Eastern populations but are quite different than those of East Asians.

Neurosyphilis in a young Indian expatriate.

Neurosyphilis is the infection of the central nervous system with treponema pallidum species, and true to its reputation as the old mimic, can present with a multitude of clinical scenarios, one of which is stroke in the young. Rare in developed countries, except for an at-risk population of drug abusers and HIV infected patients; it is still common in the rest of the world. We describe the case of a young Indian male, his presentation, diagnosis and treatment, and remarkable recovery on aqueous penicillin G therapy following his presentation with a stroke.

Disseminated Candida albicans infection in an immunocompetent host.

Candida albicans CA is an opportunistic fungus, which lives in close association with its human host. Immuno-competence is the barrier to its tendency to invade. Normal skin, commensal bacteria and neutrophils are the first hurdles and once broken down by indwelling catheters, antibiotics or ablative chemotherapies, dissemination can occur with grave consequences. We describe a young patient with apparent full immune competence, who suffered from disseminated CA infection, her presentation, diagnosis and therapy with amphotericin B deoxycholate, which lead to her complete recovery and return to a productive life.

Combined brucella melitensis and streptococcal viridans endocarditis.

Infectious endocarditis is a potentially lethal inflammation of the hearts' inner lining invaded by microorganisms. The mortality from this illness increases as the number of infective organisms rises to 2, due to involvement of the left side of the heart. These microorganisms usually arise from the patient's own flora but can be acquired from the environment. Fever and heart murmurs are the principal clinical manifestations followed by a plethora of peripheral signs due to dissemination of microorganisms via the bloodstream. Echocardiographic imaging and sensitive culture techniques form the cornerstone of diagnosis. We report a patient with rheumatic heart disease who had combined brucella melitensis and streptococcus viridans endocarditis complicated by heart failure and an aortic root abscess. He was diagnosed on the basis of a history of prolonged fever and occupational risk as a shepherd, the presence of heart murmurs, positive blood cultures and echocardiographic evidence of aortic vegetations. He had an excellent response to intravenous antibiotic therapy combined with aortic valve replacement, which nowadays is regarded as the safest therapeutic approach for aortic valve endocarditis.

Traumatic fat embolism syndrome.

Traumatic fat embolism syndrome occurs most often following fractures of long bones sustained in road traffic accidents and is a common cause of medical consultation from the orthopedic surgery department. The sub-clinical presentation is subtle and expresses itself by the presence of hypoxemia, while the full clinical syndrome compromises respiratory insufficiency, an altered consciousness and a characteristic petechial rash. Recognition is simple once the patient is viewed in the context of his or her clinical setting. Diagnosis is aided further by the presence of hematological and biochemical abnormalities including anemia, thrombocytopenia, an elevated erythrocyte sedimentation rate and fat macroglobulinemia. Imaging by chest radiograph, computed tomography or magnetic resonance of the brain is used to confirm the extent of the respective organ involvement and to exclude alternative pathologies. The release of free fatty acids into the circulation and their subsequent effects is the key pathological event. Treatment is based on supportive care and high-dose corticosteroid therapy. We report a patient with traumatic fat embolism syndrome who developed the syndromes classical symptoms and signs following fracture of the long bones of his left lower leg. Admission to an intensive care unit, mechanical ventilatory support with positive end-expiratory pressure and corticosteroid therapy lead to his improvement and allowed eventual open reduction and internal fixation and discharge of our patient. Modern therapy offers a relatively good prognosis for patients with traumatic fat embolism syndrome; the optimal dose and timing of corticosteroid therapy in prophylaxis and treatment however, remain the subject of intense debate.