Case Report: Hepatic Adenomatosis in a Patient With Prader-Willi Syndrome.

Prader-Willi syndrome (PWS) is a genetic disorder caused by the lack of expression of genes on the paternally inherited chromosome region 15q11.2-q13. It is a multisystem disorder that is characterized by severe hypotonia with poor suck and feeding difficulties in early infancy, followed in early childhood by excessive eating and gradual development of morbid obesity. The incidence of type 2 diabetes mellitus is high, particularly in obese patients. Non-alcoholic fatty liver disease has also been reported in some patients with PWS. Liver adenomatosis is a benign vascular lesion of the liver, defined by the presence of >10 adenomas, in the otherwise healthy liver parenchyma. We report the first case of a patient with PWS with severe obesity, type 2 diabetes mellitus, and non-alcoholic fatty liver who also developed liver adenomatosis, review the pediatric literature on liver adenomatosis, and discuss the potential underlying mechanisms.

The clinical and genetic characteristics of permanent neonatal diabetes (PNDM) in the state of Qatar.

BACKGROUND: Neonatal diabetes mellitus (NDM) is a rare condition that occurs within the first six months of life. Permanent NDM (PNDM) is caused by mutations in specific genes that are known for their expression at early and/or late stages of pancreatic beta- cell development, and are either involved in beta-cell survival, insulin processing, regulation, and release. The native population in Qatar continues to practice consanguineous marriages that lead to a high level of homozygosity. To our knowledge, there is no previous report on the genomics of NDM among the Qatari population. The aims of the current study are to identify patients with NDM diagnosed between 2001 and 2016, and examine their clinical and genetic characteristics. METHODS: To calculate the incidence of PNDM, all patients with PNDM diagnosed between 2001 and 2016 were compared to the total number of live births over the 16-year-period. Whole Genome Sequencing (WGS) was used to investigate the genetic etiology in the PNDM cohort. RESULTS: PNDM was diagnosed in nine (n = 9) patients with an estimated incidence rate of 1:22,938 live births among the indigenous Qatari. Seven different mutations in six genes (PTF1A, GCK, SLC2A2, EIF2AK3, INS, and HNF1B) were identified. In the majority of cases, the genetic etiology was part of a previously identified autosomal recessive disorder. Two novel de novo mutations were identified in INS and HNF1B. CONCLUSION: Qatar has the second highest reported incidence of PNDM worldwide. A majority of PNDM cases present as rare familial autosomal recessive disorders. Pancreas associated transcription factor 1a (PTF1A) enhancer deletions are the most common cause of PNDM in Qatar, with only a few previous cases reported in the literature.

Treatment results of neo-adjuvant chemotherapy in advanced head and neck cancer in Oman.

BACKGROUND AND OBJECTIVES: A prospective, single-arm study was carried out to evaluate the safety and efficacy of neo-adjuvant chemotherapy in advanced head and neck cancer (HNC) in Oman. MATERIALS AND METHODS: The study was carried out in the Oncology and Ear, Nose and Throat (ENT) Departments, Muscat, Oman between October 1998 and December 2001. Eligible, previously untreated patients with confirmed diagnosis of locally advanced non-metastatic carcinoma of the head and neck were examined. A maximum of three cycles of neo-adjuvant chemotherapy (Cisplatin 100mg/m2 Day 1 plus 5-Fluorouracil 1gm/m2 continuous infusion for four days) were administered, followed by radical radiotherapy according to primary site. The main end-points were toxicity, response rate, disease-free survival and overall survival. RESULTS: Seventy-three patients (45 males and 28 females) were eligible; all were evaluable for response and toxicity. The median age of studied patients was 52 years (range: 17-83 years). Forty-four patients (60%) had stage III disease and 29 (40%) had stage IV disease. After neo-adjuvant chemotherapy, Overall Response (OR) [Complete Response (CR) + Partial Response (PR)] was observed in 50 patients (68%), 33 patients (45%) had clinical CR and 17 patients (23%) had PR. Sixteen patients (22%) showed Stable Disease (SD) and 7 patients (10%) progressed while on chemotherapy. After completion of radiotherapy, the OR rate was 80%. Forty patients (55%) had clinically confirmed CR, 18 (25%) had PR, 9 patients (12%) had SD and 6 patients (8%) had progressive disease (PD). The median follow-up period was 16 months (range 3-48 months). The initial response to chemotherapy had a significant effect on survival (p= 0.011). The nasopharyngeal primary was significantly associated with high CR and longer survival (p= 0.01 and 0.02 respectively). CONCLUSIONS: Head and neck carcinoma is not a common malignancy in Oman. The treatment results with cisplatin and 5-FU compare favorably to similar international studies and treatment-related toxicities are tolerable.