A rare case of Evans syndrome associated with sudden loss of vision: A case report.

PURPOSE: To report a case of Evans syndrome with a vascular occlusive event leading to severe loss of vision. CASE REPORT: A 12-year-old boy with Evans syndrome presented with painless acute loss of vision in the left eye during a period of remission from the disease. Examination showed visual acuity of hand motion in the left eye, left relative afferent pupillary defect, pale optic nerve head, and attenuated vessels. Optical coherence tomography showed thin macula in both eyes, and fundus fluorescein angiography revealed delayed filling time of the arterial phase in the left eye, with attenuation and sclerosis of the arterioles. An electrophysiological study showed an electronegative electroretinogram. Based on these findings, we reached a concurrent diagnosis of atypical retinitis pigmentosa in both eyes along with a major superimposed vascular occlusive event in the left eye leading to severe visual loss. CONCLUSION: This is a case describing a rare ocular complication of Evans syndrome, leading to severe loss of vision due to vascular occlusion of unknown mechanism.

Evaluation of endocrine complications in beta-thalassemia intermedia (ß-TI): a cross-sectional multicenter study.

BACKGROUND: Data on the prevalence and type of endocrine disorders in ß-thalassemia intermedia (ß-TI) patients are scarce. This multicenter study was designed to determine the prevalence of endocrine complications and the associated risk factors in a large group of ß-TI patients. METHODS: In this cross-sectional multicenter study, 726 ß-TI patients, aged 2.5-80 years, registered at 12 thalassemic centers, from nine countries, were enrolled during 2017. In a subgroup of 522 patients (mean age 30.8 ± 12.1; range: 2.5-80 years) from Qatar, Iran, Oman, Cyprus, and Jordan detailed data were available. RESULTS: Overall, the most prevalent complications were osteopenia/osteoporosis (22.3%), hypogonadism (10.1%), and primary hypothyroidism (5.3%). In the subgroup multivariate analysis, older age was a risk factor for osteoporosis (Odds ratio: 7.870, 95% CI: 4.729-13.099, P < 0.001), hypogonadism (Odds ratio: 6.310, 95% CI: 2.944-13.521, P < 0.001), and non-insulin-dependent diabetes mellitus (NIDDM; Odds ratio: 17.67, 95% CI: 2.217-140.968, P = 0.007). Splenectomy was a risk factor for osteoporosis (Odds ratio: 1.736, 95% CI: 1.012-2.977, P = 0.045). Hydroxyurea was identified as a "protective factor" for NIDDM (Odds ratio: 0.259, 95% CI: 0.074-0.902, P = 0.034). CONCLUSIONS: To the best of our knowledge, this is the largest cohort of ß-TI patients with endocrine disorders evaluated in extremely heterogenic thalassemic populations for age, clinical, hematological, and molecular composition. The study demonstrates that endocrine complications are less common in patients with ß-TI compared with ß-TM patients. However, regular monitoring with timely diagnosis and proper management is crucial to prevent endocrine complications in ß-TI patients.

An ICET- A survey on Hypoparathyroidism in Patients with Thalassaemia Major and Intermedia: A preliminary report.

Hypoparathyroidism (HPT) is a rare disease with leading symptoms of hypocalcemia, associated with high serum phosphorus levels and absent or inappropriately low levels of parathyroid hormone (PTH). In patients with thalassemias it is mainly attributed to transfusional iron overload, and suboptimal iron chelation therapy. The main objectives of this survey were to provide data on the prevalence, demographic and clinical features of HPT in thalassemia major (TM) and intermedia (TI) patients living in different countries, and to assess its impact in clinical medical practice. A questionnaire was sent to all Thalassemia Centres participating to the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescence Medicine (ICET-A) Network.Seventeen centers, treating a total of 3023 TM and 739 TI patients, participated to the study. HPT was reported in 206 (6.8%) TM patients and 33 (4.4%) TI patients. In general, ages ranged from 10.5 to 57 years for the TM group and from 20 to 54 years for the TI group. Of the 206 TM patients and 33 TI patients with HPT, 117 (48.9%) had a serum ferritin level >2.500 ng/ml (54.3% TM and 15.1% TI patients) at the last observation. Hypocalcemia varied in its clinical presentation from an asymptomatic biochemical abnormality to a life-threatening condition, requiring hospitalization. Calcium and vitamin D metabolites are currently the cornerstone of therapy in HPT. In TM patients, HPT was preceded or followed by other endocrine and non-endocrine complications. Growth retardation and hypogonadism were the most common complications (53.3% and 67.4%, respectively). Although endocrine complications were more common in patients with TM, non-transfused or infrequently transfused patients with TI suffered a similar spectrum of complications but at a lower rate than their regularly transfused counterparts.In conclusion, although a large international registry would help to better define the prevalence, comorbidities and best treatment of HPT, through the result of this survey we hope to give a clearer understanding of the burden of this disease and its unmet needs. HPT requires lifelong therapy with vitamin D or metabolites and is often associated with complications and comorbidities.Therefore, it is important for endocrinologists and other physicians, who care for these patients, to be aware of recent advances of this disorder.

Gastrointestinal Findings in the Largest Series of Patients With Hereditary Biallelic Mismatch Repair Deficiency Syndrome: Report from the International Consortium.

OBJECTIVES: Hereditary biallelic mismatch repair deficiency (BMMRD) is caused by biallelic mutations in the mismatch repair (MMR) genes and manifests features of neurofibromatosis type 1, gastrointestinal (GI) polyposis, and GI, brain, and hematological cancers. This is the first study to characterize the GI phenotype in BMMRD using both retrospective and prospective surveillance data. METHODS: The International BMMRD Consortium was created to collect information on BMMRD families referred from around the world. All patients had germline biallelic MMR mutations or lack of MMR protein staining in normal and tumor tissue. GI screening data were obtained through medical records with annual updates. RESULTS: Thirty-five individuals from seven countries were identified with BMMRD. GI data were available on 24 of 33 individuals (73%) of screening age, totaling 53 person-years. The youngest age of colonic adenomas was 7, and small bowel adenoma was 11. Eight patients had 19 colorectal adenocarcinomas (CRC; median age 16.7 years, range 8-25), and 11 of 18 (61%) CRC were distal to the splenic flexure. Eleven patients had 15 colorectal surgeries (median 14 years, range 9-25). Four patients had five small bowel adenocarcinomas (SBC; median 18 years, range 11-33). Two CRC and two SBC were detected during surveillance within 6-11 months and 9-16 months, respectively, of last consecutive endoscopy. No patient undergoing surveillance died of a GI malignancy. Familial clustering of GI cancer was observed. CONCLUSIONS: The prevalence and penetrance of GI neoplasia in children with BMMRD is high, with rapid development of carcinoma. Colorectal and small bowel surveillance should commence at ages 3-5 and 8 years, respectively.

Genetic and clinical determinants of constitutional mismatch repair deficiency syndrome: report from the constitutional mismatch repair deficiency consortium.

BACKGROUND: Constitutional mismatch repair deficiency (CMMRD) is a devastating cancer predisposition syndrome for which data regarding clinical manifestations, molecular screening tools and management are limited. METHODS: We established an international CMMRD consortium and collected comprehensive clinical and genetic data. Molecular diagnosis of tumour and germline biospecimens was performed. A surveillance protocol was developed and implemented. RESULTS: Overall, 22/23 (96%) of children with CMMRD developed 40 different tumours. While childhood CMMRD related tumours were observed in all families, Lynch related tumours in adults were observed in only 2/14 families (p=0.0007). All children with CMMRD had café-au-lait spots and 11/14 came from consanguineous families. Brain tumours were the most common cancers reported (48%) followed by gastrointestinal (32%) and haematological malignancies (15%). Importantly, 12 (30%) of these were low grade and resectable cancers. Tumour immunohistochemistry was 100% sensitive and specific in diagnosing mismatch repair (MMR) deficiency of the corresponding gene while microsatellite instability was neither sensitive nor specific as a diagnostic tool (p<0.0001). Furthermore, screening of normal tissue by immunohistochemistry correlated with genetic confirmation of CMMRD. The surveillance protocol detected 39 lesions which included asymptomatic malignant gliomas and gastrointestinal carcinomas. All tumours were amenable to complete resection and all patients undergoing surveillance are alive. DISCUSSION: CMMRD is a highly penetrant syndrome where family history of cancer may not be contributory. Screening tumours and normal tissues using immunohistochemistry for abnormal expression of MMR gene products may help in diagnosis and early implementation of surveillance for these children.

MECC regional initiative in pediatric palliative care: Middle Eastern course on pain management.

In all the major medical centers throughout the Middle East, there is a functioning pediatric hematology oncology department. In almost all countries, opioids such as morphine, oxycodone, and fentanyl are available. Pediatric palliative care services are still in their infancy and await further recognition and development. Unfortunately, there are still countries in the Middle East where children with cancer are diagnosed when the disease is already at stage III or IV, when the only option left is palliation. To decrease the incidence of late presentation, more effort is needed concerning public awareness, and concomitantly, an urgent need to develop hospital-based and community-based palliative and supportive care services. The initial step in this direction would involve more training of health care providers: Pediatricians, Pediatric Oncologists, Oncology Nurses, and Social Workers with updated pharmacological and nonpharmacological modalities of treatment.

Pediatric oncology situation analysis (Jordan).

This article highlights the current situation of pediatric oncology in Jordan by reviewing the available population based data from the surveillance. Cancer among children aged less than 15 years make up 4 to 6% of all registered new cancer cases in all ages each year. The major types of cancer in females for the year 2008 are leukemia 32.2%, central nervous system 18.8%, skeletal and soft tissue 8.8%, lymphomas 5.5%, and sympathetic 5.5%, whereas in males, they are leukemia 28.1%, central nervous system 18.8%, lymphomas 16.2%, skeletal and soft tissue 7% and sympathetic 6.3%. Children with cancer receive treatment through pediatric oncology wards in King Hussein Cancer Center (KHCC) and Royal Medical Services hospital or through pediatric departments in King Abdullah university Hospital and Princes Rahma hospital with full government coverage of the treatment expenses. Currently the pediatric palliative care program is limited to KHCC which provides inpatient care, and out-patients and drop-in care on a daily basis to provide symptom management, counseling, and other services as appropriate. The lack of palliative care in other hospital and pediatric home care coverage stress the need to develop special plan of action to initiate these services.

Intrauterine upper limb ischemia associated with fetal thrombophilia: a case report and review of the literature.

Neonatal extremity gangrene is rare, even rarer are those born with evidence of intrauterine vascular occlusion. Intrauterine limb ischemia has been attributed to several etiological factors which include thromboembolic disease occluding the arteries of the affected limb or compression of the limb during intrauterine life. In this report, we present a case of brachioradial arterial thrombosis associated with mild homocysteinemia and double heterozygosity of methylenetetrahydrofolate reductase 677C-T and factor V Leiden gene mutations. We suggest investigating the neonates and their mothers for possible genetic prothrombotic risk factors when they present with intrauterine thrombosis as this issue is important for management and counseling.

Mediterranean glucose-6-phosphate dehydrogenase (G6PD(C563T)) mutation among Jordanian females with acute hemolytic crisis.

OBJECTIVE: To evaluate the G6PD(C563T) Mediterranean mutation among Jordanian females who were admitted to Princess Rahma Teaching Hospital (PRTH) with/or previous history of favism. STUDY DESIGN: A descriptive study. PLACE AND DURATION OF STUDY: Jordanian University of Science and Technology and PRTH, from October 2003 to October 2004. METHODOLOGY: After obtaining approval from the Ethics Committee of Jordanian University of Science and Technology, a total of 32 females were included in this study. Samples from 15 healthy individual females were used as a negative control. Blood samples from these patients were collected and analyzed by allele-specific polymerase chain reaction (AS-PCR) to determine the G6PD(C563T) mutation. RESULTS: Twenty one out of 32 patients were found to be G6PD(C563T) Mediterranean mutation (65.6%) positive. Three out of 21 patients were homozygous and remaining 18 were heterozygous for G6PD(C563T) Mediterranean mutation. Eleven (34.4%) out of 32 patients were found to be negative for G6PD(C563T) mutation indicating the presence of other G6PD mutations in the study sample. CONCLUSION: G6PD(C563T) Mediterranean mutation accounted for 65.6% of the study sample with favism in the North of Jordan. There is likely to be another G6PD deficiency variant implicated in acute hemolytic crisis (favism).

Idiopathic hypertrophic pachymeningitis in a child with hydrocephalus.

Idiopathic hypertrophic pachymeningitis is a rare but increasingly recognized disorder characterized by diffuse thickening of the dura mater of unknown etiology. The inflammation usually involves the cranial or spinal dura mater, with resultant neurologic deficits. Although it is reported primarily in adults, there is one previous report describing the condition in a child. Described here is the case of a child who presented at the age of 3.5 years with idiopathic hypertrophic pachymeningitis involving the entire central nervous system, with poor response to steroids, cyclophosphamide, and intraventricular cytarabine.

Predictors of severe hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency following exposure to oxidant stresses.

BACKGROUND AND OBJECTIVES: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a genetic enzymatic disorder that affects millions of people worldwide, and is a major health problem in Jordan. We studied factors that may predict severe hemolysis in children with G6PD deficiency. METHODS: We reviewed the records of patients with low G6PD activity admitted to a teaching hospital be- tween 1996 to 2007. We collected demographic data, details of sign and symptoms, history and type of fava bean ingestion, blood and Rh group, history of neonatal jaundice, history and type of drug use, abdominal pain at admission and the results of tests for hemoglobin, white blood cells (WBC), and hepatic function. We classified patients into mild and severe groups based on hemoglobin levels at admission. RESULTS: Of 428 children with G6PD deficiency, 79 (18%) were severe cases and 349 (82%) patients with mild disease. There were no statistically significant differences in most factors between the two groups. Factors that achieved statistical significance for severe hemolysis included younger age (P<.05), male gender (P<.05), higher alkaline phosphatase (ALP) (P<.05), presence of fever at admission (P<.01), presence of vomiting during the at- tack (P=.006), and a negative family history for G6PD deficiency (P=.005). CONCLUSIONS: Severe hemolysis can be predicted during hemolytic episodes in children with low G6PD by young age, male gender, a negative family history of G6PD deficiency, the presence of fever and vomiting and a high ALP.

Sport participation in adolescents with sickle cell disease.

Adolescents with blood diseases should be encouraged to participate in exercise. Physical activity helps to build stronger muscles, to give better support to the joints, and to improve the patient's overall health and fitness. It also improves emotional well being by improving self-esteem and providing social interaction. Sports and exercise in sickle cell anemia and sickle cell trait need special consideration. Young athletes with sickle cell disease are at high risk of dehydration, heat-related injury, exhaustion, painful episodes, and hip joint problems. Gradual acclimatization to heat, humidity and high altitude, slow conditioning over weeks and avoidance of dehydration are recommended for all adolescents with sickle cell disease to make their sport activity safe. Effort should be made to educate those with sickle cell disease that their condition is not a handicap and that they are fit to lead a normal life.

Pubertal evaluation of adolescent boys with beta-thalassemia major and delayed puberty.

OBJECTIVE: To examine the hormonal status of the hypothalamic-pituitary-gonadal axis in adolescent males with beta-thalassemia major. DESIGN: Controlled clinical study. SETTING: Tertiary referral teaching hospital. PATIENT(S): Thirty-three adolescent males with beta-thalassemia major. INTERVENTION(S): Basal LH, FSH, and T were examined. All individuals received 100 microg GnRH analogue. Four hours later the hormone levels were retested. Patients with beta-thalassemia and low T levels received hCG. MAIN OUTCOME MEASURE(S): The preintervention and postintervention levels of FSH, LH, and T were examined. RESULT(S): Of the 33 beta-thalassemia major adolescents, 17 had delayed puberty. The difference in basal LH, FSH, and T levels between delayed and normal puberty beta-thalassemia groups were statistically significant. These levels were significantly lower compared with the constitutional delayed puberty group and become even more significant after GnRH analogue administration. The T levels in the beta-thalassemia group were significantly lower than in the control group. After hCG administration, the T levels remained significantly lower in the delayed-puberty beta-thalassemia compared to the normal-puberty beta-thalassemia group. CONCLUSION(S): Despite recent therapeutic advances in the management of beta-thalassemia major, the risk of secondary endocrine dysfunction remains high. Hypogonadism is one of the most frequent endocrine complications.

Emergency peripartum hysterectomy in Northern Jordan: indications and obstetric outcome (an 8-year review).

OBJECTIVE: To review cases of emergency peripartum hysterectomy regarding their incidence, risk factors, indications and complications and their results were carefully analysed. MATERIALS AND METHODS: A retrospective study of cases of emergency peripartum hysterectomy which were performed in the period between February 1994 and February 2002 at the Princess Badeea Teaching Hospital in Northern Jordan. Demographic and clinical data were extracted and closely interpreted RESULTS: In the study period there were a 70,252 deliveries and 61 cases of emergency peripartum hysterectomies. The overall incidence was 0.87 peripartum hysterectomies per 1,000 deliveries. There were 50 cases (82%) delivered by caesarean section and 11 cases (18%) were delivered vaginally. Caesarean hysterectomy was performed in 50 cases and postpartum hysterectomy was performed in 11 cases. Total hysterectomy was performed in 39 cases (64%) and subtotal hysterectomy was performed in 22 cases (36%). The main indications for hysterectomy were morbidly adherent placenta (47.5%), ruptured uterus (27.9%) and uncontrollable haemorrhage from uterine atony (21.3%). There were two maternal deaths and 7 cases of stillbirths and 4 cases of early neonatal deaths. CONCLUSION: Peripartum hysterectomy is a dramatic with high risk but a life saving operation. It is usually associated with significant maternal and fetal morbidity and mortality. Obstetricians should identify patients at risk and anticipate the procedure and complications, as early intervention and proper management facilitate optimal outcome.