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Glycogen storage diseases (GSDs) are a group of carbohydrate metabolism disorders, most of which are inherited in autosomal recessive patterns. GSDs are of two types: those that have to do with liver and hypoglycaemia (hepatic GSDs) and those that are linked to neuromuscular presentation. This study aims to assess the impact of dietary intervention, including medium-chain triglyceride (MCT) oil, on anthropometric measurements, body composition analysis and metabolic parameters among Jordanian children and is expected to be the first in the country. A sample of 38 children with glycogen storage disease type 1 (GSD-1) (median age = 6.4 years) were on a diet that included uncooked cornstarch therapy and a fructose-, sucrose- and lactose-restricted diet. Patients started to take MCT oil along with the prescribed diet after the first body composition test. Patients' nutritional status was re-evaluated three months later. The study results show that the percentage of patients who suffered from hypoglycaemia at the beginning of the study decreased significantly from 94.7% to 7.9% ( p < 0.0001). The serum levels of triglycerides, cholesterol, uric acid and lactate decreased significantly after three months of intervention (100-71.1%, 73.7-21.1%, 97.4-52.6% and 94.7-18.4%, respectively). In contrast, there was no statistical difference in neutrophil count. Regarding clinical parameters, liver span was significantly reduced from (16.01 ± 2.65 cm) to (14.85 ± 2.26 cm) ( p < 0.0001). There were significant improvements in growth parameters, including height-for-age and BMI-for-age for children aged ≥2 years ( p = 0.034 and p = 0.074, respectively). Significant improvements in skeletal muscle mass and bone mineral content were also noticed at the end of the trial ( p ≤ 0.05). In conclusion, medium-chain triglyceride therapy is found to improve biochemical and growth parameters in children with GSD-1 in Jordan.

Introduction: Within the Canadian competency-based medical education system, entrustable professional activities (EPAs) are used to assess residents on performed clinical duties. This study aimed to determine whether implementing a bundle of two interventions (a case-based discussion intervention and a rotation-based nudging system) could increase the number of EPA assessments that could occur for our trainees., Methods: The authors designed an intervention bundle with two components: 1) a case-based workshop where trainees discussed which EPAs could be assessed with multiple cases and 2) a nudging system wherein each trainee was reminded of EPAs that would be useful to them on each rotation in their first year. We conducted a retrospective program evaluation to compare the intervention cohort (2019) to two historical cohorts using similar EPAs (2017, 2018)., Results: Data from 22 trainees (seven in 2017, eight in 2018, and seven in 2019) were analyzed. There was a marked increase in the total number of EPA assessments acquired in the 2019 cohort (average per resident = 285.7, 95% confidence interval [CI] = 256.1 to 312.3, range = 195-350) compared to the two other years (2018 [average = 132.4, 95% CI = 107.5 to 157.02, range = 107-167] and 2017 [70.1, 95% CI 45.3 to 91.0, range = 49-95]), yielding an effect size of Cohen's d = 4.02 for our intervention bundle., Conclusions: Within the limitations of a small sample size, there was a strong effect of introducing two interventions (a case-based orientation and a nudging system) upon EPA assessments with PGY-1 residents. These strategies may be useful to others seeking to improve EPA assessment numbers in other specialties and clinical environments., Competing Interests: Dr. Chan holds a grant from the Royal College of Physicians and Surgeons of Canada on the topic of entrustable professional activities in competency‐based medical education. For unrelated work, Dr. Chan receives a teaching stipend for her work as the chief strategic officer of the ALiEM Faculty Incubator program. She has also received research funding from the PSI Foundation for work on social media knowledge translation and education. The other authors have no potential conflicts to disclose., (© 2021 by the Society for Academic Emergency Medicine.)

Background: Data on the prevalence and type of endocrine disorders in β-thalassemia intermedia (β-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 β-TI patients., Methods: In this cross-sectional multicenter study, 726 β-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 β-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 β-TI compared with β-TM patients. However, regular monitoring with timely diagnosis and proper management is crucial to prevent endocrine complications in β-TI patients.

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.

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.

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., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

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.

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.

Lung function abnormality is a known complication of thalassemia, but the results of studies in pulmonary function have been inconsistent. This study was conducted to describe the type of lung impairment in thalassemic children. Pulmonary function tests were conducted in 40 children with beta-thalassemia major, 23 males and 17 females. Tests included spirometry, total lung capacity (TLC), single breath diffusing capacity of the lung for carbon monoxide (DL(CO)) and arterial blood gases. Serum ferritin level was measured in all children to study its relationship to lung function impairment. A predominantly restrictive pattern was seen in 14 patients (35%). These patients had a significant reduction in RV, FVC, TLC and PEF with an FEV1/FVC ratio of more than 75%. Obstructive airway disease was found in six patients (15%), with an FEV1/FVC ratio less than 75%, increased RV and reduced FEF(25%-75%). Impairment of diffusion was found in 10 patients (25%), with DL(CO) reduced to less than 80% of the predicted value. Arterial blood gases results showed that no patient was hypoxic. No correlation was found between the severity of restrictive or obstructive disease and the serum ferritin level. There was a significant linear correlation between age and serum ferritin level (P < 0.019). Patients with thalassemia have a predominantly restrictive lung dysfunction pattern. This may be due to pulmonary parenchymal pathology, although the reason for the obstructive pattern seen in a small proportion of patients remains obscure.

The objective of this study was to evaluate the rate of acute splenic sequestration (ASSC) in patients with sickle beta-thalassaemia and sickle cell anaemia, the risk of recurrence in those who survive the first episode, and the relationship between ASSC episodes and subsequent hypersplenism. All patients with confirmed diagnosis of sickle cell disease at a tertiary referral teaching hospital, between January 1994 and December 2002 were interviewed and had their medical records reviewed. Seventy-seven patients with sickle cell disease were identified. Their ages ranged between 2 and 18 years (mean, 10.1 years). There were 35 females and 38 males. Thirty-seven (50.6%) had sickle beta-thalassaemia, and 36 (49.4%) had homozygous sickle cell anaemia. Of these, 26 had high level of Hb F and 11 had normal level of fetal haemoglobin (Hb F). Twenty-one patients (28%) had 63 episodes of acute splenic sequestration. Thirty-seven episodes were experienced by 12 patients with sickle beta-thalassaemia; of these 11 were major attacks with one fatality. Twenty-six episodes were experienced by nine patients with sickle cell anaemia. Splenomegaly and hypersplenism were greater in the acute splenic sequestration group than in the rest of the sickle cell anaemia patients, and the differences were extremely significant. ASSC was found in nine siblings of sickle beta-thalassaemia group, while none were found in the sickle cell anaemia group. The mean age of the first episode was significantly higher in sickle beta-thalassaemia, with significant differences in the levels of Hb F, Hb S, size of spleen and severity of crisis between both groups. In the sickle cell anaemia group the only significant difference between patients with and these without acute splenic sequestration was the difference in the size of spleen. In this study, the rate of ASSC in the sickle beta-thalassaemia patients was 32%, in contrast to 25% in the sickle cell anaemia patients. The risk of recurrence was about 70% in those who survived their first episodes. There was a close relationship between ASSC and subsequent hypersplenism. Important predictable factors for ASSC in sickle beta-thalassaemia patients were the presence of splenomegaly of more than 5 cm below the costal margin, history of acute splenic sequestration in siblings and high Hb F. Most of first episodes in sickle cell anaemia occur under the age of 2 years, while in sickle beta-thalassaemia the majority of patients have their first crisis at the age of > or =3.5 years.

Objective: To evaluate the function of the hypothalamic-pituitary-gonadal axis in adolescent female patients with beta-thalassemia major., Materials and Methods: A prospective study of the function of the hypothalamic-pituitary-gonadal axis function of 31 beta-thalassemia major females aged between 13 and 22 years and in 12 control females aged between 12 and 22 years. All were treated at Princess Rahma Teaching Hospital, Irbid, Northern Jordan between April 2001 and April 2003., Results: Of the 31 beta-thalassemia major females, 13 (41.9%) had delayed puberty. Hypothalamic-pituitary-ovarian axis dysfunction was found in 15 patients (48.4%). Twelve patients (38.7%) had hypogonadotropic hypogonadism and 5 (16.1%) had ovarian failure. High levels of serum ferritin were significantly higher in patients with delayed puberty., Conclusion: Pituitary and ovarian dysfunction are common problems in beta-thalassemia major patients. The main possible cause is iron overload. This stresses the need for intensive and regular use of chelation therapy to prevent damage to the hypothalamic-pituitary-ovarian axis.

Aim: The aim of this study was to assess the prevalence and distribution of dental caries in subjects with thalassaemia major., Design: Clinical examination for dental caries, diagnosed according to the WHO criteria., Participants: A total of 54 thalassaemic patients, 23 aged 6-9 (14 males and 9 females) and 31 aged 12-18 (17 males and 14 females) were examined., Outcome Measures: dmft, DMFT and plaque scores., Results: The mean dmft was 6.92 for 6-7 year olds and 4.72 for 8-9 year olds. The DMFT values were 6.57 and 5.95 for ages 12-14 and 15-18, respectively. There was no statistically significant difference in caries prevalence (dmft/DMFT) between gender or between primary and permanent teeth. Only 17.4 per cent of the children aged 6-9 and 21.4 per cent of 12-18 years olds were caries free. The prevalence of dental caries in the thalassaemia patients was considerably higher (22.7 per cent) than that reported in a normal Jordanian sample (DMFT 6.26 vs 4.84). Very few fillings (1.4 per cent of the examined teeth) were observed, indicating a negligible rate of conservative treatment. More than half (61.1 per cent) of the patients had poor oral hygiene (plaque score > or = 2.0)., Conclusions: The need for effective preventive measures, education and dental treatment need to be stressed for this caries risk group.

The aetiology and complications of exchange transfusion (ET) were studied over a 6-year period in northern Jordan. During that time, 336 neonates (0.46% of total live births) underwent 386 ETs. There was a yearly reduction in the number of ETs, varying from 8.2% in the 1st year of the study to 2.7% in the last year. Thirty-nine (11.9%) required more than one ET. Twenty-five (7.4%) were preterm babies and the remainder full-term. The commonest cause of ET overall was G6PD deficiency, either alone or concomitant with ABO incompatibility (38.1%). ET complications occurred in 51 neonates (15.2%), the commonest being anaemia and bradycardia. Septicaemia occurred in only 3% of cases. Only one baby died. G6PD deficiency, either alone or concomitant with ABO isoimmunization, is the most common cause of ET in northern Jordan. Fewer preterm babies require ET and there is a low incidence of septicaemia following ET.

The effectiveness of desferrioxamine (DFO) in ameliorating the severity of the acute haemolysis of glucose-6-phosphate dehydrogenase (G6PD) deficiency was studied in 167 children with G6PD deficiency during an acute haemolytic crisis. All patients received packed cell transfusion on admission if their Hb levels were <8 g/dl, which was repeated as needed. Eighty patients also received a single dose of DFO 30-40 mg/kg by slow intravenous infusion (DFO group). The remaining 87 children did not receive DFO (control group). The need for more than one transfusion was less frequent in the DFO group as compared to the control group (p = 0. 01). The need for late transfusion (transfusion after 36 h of admission) was also less in the DFO group (7%) compared to 21% in the control group (p = 0.02). On average, children in the DFO group needed less packed red blood cells (16.5 ml/kg body weight) than the control group (22.8 ml/kg body weight) and the difference was highly significant (p = 0.0001). We conclude from this study that DFO in a small dose is effective in the treatment of acute haemolytic crises of G6PD deficiency. It shortens the duration of the crisis and decreases the amount of blood transfusion needed.

Unlabelled: Often the first evidence of variation from normal in human dentition is an observable difference in the color of the teeth. During the past decade, the demand for conservative esthetic dentistry has grown dramatically. Tooth discoloration is a frequent dental finding, associated with clinical and esthetic problems. It differs in etiology, appearance, composition, location, severity, and firmness in adherence to the tooth surface. Basically, there are two types of tooth discolorations: those caused by extrinsic factors and those caused by intrinsic congenital or systemic influence. The intensity of stains may be worsened if there are enamel defects. Tooth discoloration presents two major challenges to the dental team. The first challenge is to ascertain the cause of the stain; the second is its management., Clinical Significance: This article reviews the etiology and clinical presentation of dental stains and outlines treatment options.

Unlabelled: Pyostomatitis vegetans is an oral eruption, characterized by small pustules, ulcers and erythematous vegetations of the labial and buccal mucosae as well as labial-attached gingivae. Its importance lies in its high correlation with inflammatory bowel disease. It is commonly associated with skin and inflammatory bowel disease and is rare in children. We here report a sister and brother with onset of the disease at the age of 5 and 7 years, respectively. It is the first report of familial pyostomatitis vegetans occurring in the youngest patients hitherto reported., Conclusion: The observation of two sibs with pyostomatitis, vegetans pyoderma gangrenosum and inflammatory bowel disease suggest a hereditary disposition to this rare triad.

Unlabelled: Pyoderma gangrenosum (PG) is a rare, poorly understood skin disease that occurs in all age groups. Less than 0.4% of patients are infants and represent a diagnostic challenge as early lesions may resemble other skin disorders. Here we report for the first time three siblings affected with PG all presenting during infancy. Unlike the older age group, the ulcers spared the legs but involved the buttocks, thighs and perianal area in all the infants., Conclusion: This is the first reported family with PG affecting three siblings suggesting autosomal recessive inheritance. The diagnosis may be more difficult in infants due to absence of underlying associated disorders and the tendency of the lesions to appear in areas where infants frequently have other dermatoses. PG characteristically involves the buttocks, thighs and perianal area and spares the legs.

Homozygous sickle cell anaemia (SCA) is an inherited red blood cell disorder in which haemoglobin A is replaced by haemoglobin S. The disease exhibits a wide spectrum of clinical behaviour which has been well described in neighbouring countries. In Jordan, however, the disease has never been characterized. We used reviews of patients' notes and clinic interviews at Princess Badi'a Teaching Hospital, Irbid, Jordan to describe the clinical presentation of the disease in our area. The total number of patients was 41 (28 boys and 13 girls) and the median age was 9 years (range 1.5-21). The median age at presentation was 2.5 years (range 0.5-11). The commonest presenting feature was pallor (62%). An unusual feature of the disease in this series is the presence of a palpable spleen in 44% of patients older than 8 years. Associated G6PD deficiency was present in 29% of boys. Different clinical patterns of SCA were observed. Haemoglobin F is unlikely to be an explanation for this variability since it has not been shown to correlate with a number of severity indices of the disease such as the frequency of blood transfusions, hospitalizations and painful crises. Although the disease haplotype is not known in Jordan, our geographical location between Asia and Africa may suggest the presence of more than one haplotype and consequently different clinical patterns.

A prospective study was undertaken over a 1-year period in northern Jordan to determine the incidence, causes and characteristics of neonatal septicaemia which is a major cause of mortality and morbidity in newborns. The study identified 47 septicaemic neonates, representing an incidence of 2.3/1000 live births. Respiratory distress and hyperbilirubinaemia were the prominent presenting clinical findings. Gram-negative organisms were cultured from 46 neonates with Klebsiella species, accounting for 64% of cases. There were no cases of infection with group B Streptococcus or Listeria monocytogenes. The overall mortality rate was 40%. Prematurity and low birthweight, early onset septicaemia and concomitant meningitis were associated with high mortality. The high incidence of Gram-negative septicaemia and the antibiotic sensitivity pattern of the organisms indicated the use of cefotaxime or ceftazidime as initial therapy while awaiting culture results. Continued surveillance of neonatal septicaemia is mandatory due to temporal changes in the causative organisms and their antibiotic sensitivity.

We report two successful pregnancies in a 17-year-old Arab girl who had received modern combination chemotherapy and central nervous system minimal disease therapy for childhood acute lymphoblastic leukaemia at the age of 9.5 years.