Analysis of disease characteristics of a large patient cohort with congenital generalized lipodystrophy from the Middle East and North Africa.

BACKGROUND: Congenital generalized lipodystrophy (CGL) is a rare inherited disease characterized by a near-total absence of adipose tissue and is associated with organ system abnormalities and severe metabolic complications. Here, we have analyzed the disease characteristics of the largest CGL cohort from the Middle East and North Africa (MENA) who have not received lipodystrophy-specific treatment. METHODS: CGL was diagnosed clinically by treating physicians through physical assessment and supported by genetic analysis, fat loss patterns, family history, and the presence of parental consanguinity. Data were obtained at the time of patient diagnosis and during leptin-replacement naïve follow-up visits as permitted by available medical records. RESULTS: Data from 43 patients with CGL (37 females, 86%) were collected from centers located in eight countries. The mean (median, range) age at diagnosis was 5.1 (1.0, at birth-37) years. Genetic analysis of the overall cohort showed that CGL1 (n = 14, 33%) and CGL2 (n = 18, 42%) were the predominant CGL subtypes followed by CGL4 (n = 10, 23%); a genetic diagnosis was unavailable for one patient (2%). There was a high prevalence of parental consanguinity (93%) and family history (67%) of lipodystrophy, with 64% (n = 25/39) and 51% (n = 20/39) of patients presenting with acromegaloid features and acanthosis nigricans, respectively. Eighty-one percent (n = 35/43) of patients had at least one organ abnormality; the most frequently affected organs were the liver (70%, n = 30/43), the cardiovascular system (37%, n = 16/43) and the spleen (33%, n = 14/43). Thirteen out of 28 (46%) patients had HbA1c > 5.7% and 20/33 (61%) had triglyceride levels > 2.26 mmol/L (200 mg/dl). Generally, patients diagnosed in adolescence or later had a greater severity of metabolic disease versus those diagnosed during childhood; however, metabolic and organ system abnormalities were observed in a subset of patients diagnosed before or at 1 year of age. CONCLUSIONS: This analysis suggests that in addition to the early onset of fat loss, family history and high consanguinity enable the identification of young patients with CGL in the MENA region. In patients with CGL who have not received lipodystrophy-specific treatment, severe metabolic disease and organ abnormalities can develop by late childhood and worsen with age.

Tackling access and payer barriers for growth hormone therapy in Saudi Arabia: a consensus statement for the Saudi Working Group for Pediatric Endocrinology.

Prompt diagnosis and early treatment are key goals to optimize the outcomes of children with growth hormone deficiency (GHD) and attain the genetically expected adult height. Nonetheless, several barriers can hinder prompt diagnosis and treatment of GHD, including payer-related issues. In Saudi Arabia, moderate-to-severe short stature was reported in 13.1 and 11.7 % of healthy boys and girls, respectively. Several access and payer barriers can face pediatric endocrinologists during the diagnosis and treatment of GHD in Saudi Arabia. Insurance coverage policies can restrict access to diagnostic tests for GHD and recombinant human growth hormone (rhGH) due to their high costs and lack of gold-standard criteria. Some insurance policies may limit the duration of treatment with rhGH or the amount of medication covered per month. This consensus article gathered the insights of pediatric endocrinologists from Saudi Arabia to reflect the access and payer barriers to the diagnostic tests and treatment options of children with short stature. We also discussed the current payer-related challenges endocrinologists face during the investigations of children with short stature. The consensus identified potential strategies to overcome these challenges and optimize patient management.

SGLT2i Improves Glycemic Control in Patients With Congenital Severe Insulin Resistance.

Insulin-resistant diabetes in Rabson-Mendenhall syndrome (RMS) is relatively unresponsive to first-line antidiabetic treatments, including metformin and insulin. We report 2 patients with RMS treated with 2 different sodium-glucose cotransporter inhibitors 2: empagliflozin in an 11-year-old boy and dapagliflozin in a 12-year-old girl. In the first patient, we began empagliflozin at 2.5 mg/day and increased the dose to 10 mg/day over 3 months. During treatment with empagliflozin, the amount of time during which the patient maintained serum glucose in the 70 to 180 mg/dL target range increased by 2 hours per day. Hemoglobin A1C dropped from >14% to 11.9%, urinary calcium increased almost twofold, and ß-hydroxybutyrate remained <2.5 mmol/L. Because glycemic control did not further improve with dose escalation, we reverted to the 2.5 mg/day dose. We initiated dapagliflozin in a second patient at 5 mg/day and witnessed a reduction of hemoglobin A1C from 8.5% to 6.2% after 6 months and a mild increase in urinary excretion of phosphorus but not calcium. Insulin levels fell by >50%. In 2 patients with RMS, empagliflozin and dapagliflozin were well tolerated and improved glycemic control without significantly increasing ketonemia. Renal calcium excretion should be carefully monitored.

Subcutaneous Calcification and Fixed Flexion Deformity of the Right Elbow Joint in a Child with a GNAS Mutation: A Case Report.

INTRODUCTION: The art of medicine glorifies when a clinician listens carefully to the patient's story, gives a thorough examination, performs appropriate investigations, and finally links findings together to reach a definite diagnosis. An interesting case was reported here, highlighting the integration of different symptoms and manifestations with some relevant biochemical investigations to reach a final diagnosis. To the best of our knowledge, fixed flexion deformity, as a complication of subcutaneous calcification, has not been previously reported in a child with Albright hereditary osteodystrophy (AHO). CASE PRESENTATION: A 2.5-year-old boy was born at term with a birth weight of 3.5 kg (-0.49 SDS). The child was referred to a general pediatrician with a history of right elbow joint swelling noticed initially at six months of age. He then developed the limitation of right upper arm movement, which slowly progressed afterward. The patient had no history of trauma. At nine months of age, he was diagnosed with hypothyroidism, preceded by cold skin, dry hair, and constipation. At nine years of age, he presented with a fixed flexion deformity of the right elbow associated with markedly limited joint movement and symmetrical hands with hyperpigmented knuckles of right metacarpal bones. Subcutaneous masses were felt along the right forearm, showing tenderness on palpation. Investigations revealed elevated serum parathyroid hormone and normal calcium indicating parathyroid hormone resistance. Further genetic testing revealed GNAS mutation. The child was obese throughout his childhood. CONCLUSIONS: This case report describes an obese child with subcutaneous calcification that led to fixed flexion deformity of the elbow, starting at an incredibly early age. Hypothyroidism and pseudohypoparathyroidism raised the suspicion of AHO, which was later confirmed by genetic testing. This is the first case report on fixed flexion deformity in a patient with GNAS mutation (c.719-1G > A Chr20: 57484737) in West Asia.

Use of ambulatory glucose monitoring and analysis of ambulatory glucose profile in clinical practice for diabetes management; a position statement of the Arab Society of Paediatric Endocrinology and diabetes.

BACKGROUND AND AIM: Diabetes mellitus imposes a significant burden around the world generally and in the Middle East and North Africa specifically. Glucose monitoring is a cornerstone of diabetes management. METHODS: Glycated haemoglobin has always been the main metric for assessing glycaemic control, but its use is linked with multiple pitfalls. As an alternative, continuous glucose monitoring is becoming a standard of care in many countries. Intermittent scanning glucose monitoring (isCGM) has acquired a worldwide popularity and has been proven to improve glycaemic control, hypoglycaemia detection and prevention, and quality of life. RESULTS: The most recent International Society of Paediatric and Adolescent Diabetes practice. guidelines recommended its use in young people with diabetes observing Ramadan to ensure safe fasting. At a meeting in Abu Dhabi in November 2019, the Arab Society for Paediatric. Endocrinology and Diabetes brought together a number of regional diabetes experts, patient. representatives and international expert advisors to review the evidence for isCGM and propose. guidelines for its use in the Middle East and North Africa region. CONCLUSION: In this paper, the authors strongly recommend the use of isCGM for patients in MENA and present general recommendations and compressive specific guidance for physicians and patients, which they believe will also have wider resonance.

Molecular genetics and phenotype/genotype correlation of 5-α reductase deficiency in a highly consanguineous population.

CONTEXT AND OBJECTIVES: 5-α reductase deficiency is a rare 46,XY disorder of sex development. We present detailed phenotypic and genotypic features of a cohort of 24 subjects from a highly consanguineous population of Saudi Arabia SUBJECTS AND METHODS: We studied the clinical presentation and hormonal profiles of 24 subjects diagnosed with 5-α reductase deficiency and performed genetic testing on DNA isolated from their peripheral blood using polymerase chain reaction and direct sequencing of the SRD5A2. RESULTS: All subjects had 46,XY karyotype and presented with atypical appearance of external genitalia ranging from clitoromegaly, micophallus with hypospadias, undescended testes to completely normally looking female genitalia. Thirteen (54%) of them had severe under virilization and were assigned female sex at birth. The other 11 subjects were raised as males. Stimulated Testosterone:Dihydrotestosterone ratio was high in all 16 subjects in whom it was measured. The genetic testing revealed 2 nonsense mutations (p.R103X and p.R227X) in 2 unrelated subjects, 3 missense mutations (p.P181L, p.A228T, p.R246Q) in 11 subjects and a splice site mutation (IVS1-2A > G) in 11 other subjects. There was significant phenotypic variability even in subjects with the same mutation and also within the same family. CONCLUSION: This is the first and largest report of the clinical and molecular genetics of 5-α reductase deficiency from the Middle East. It shows weak genotype/phenotype correlation and significant phenotypic heterogeneity. IVS1-2A > G mutation is the most common mutation and is likely to be a founder mutation in this part of the world.

The potential effect of technology and distractions on undergraduate students' concentration.

BACKGROUND AND OBJECTIVES: In the present era, it is difficult to keep the concentration of college students at its maximum potential during the class time, as there are many distractions that negatively impact students' concentration and prevent optimal learning. Technologies such as laptops and cell phones have invaded the classroom, raising considerable concerns about their effects on college students' attention in the classroom. Despite these concerns, no research has been done in Saudi Arabia on the effects of technology and other types of classroom distractions on students' concentration. In the current study, we have attempted to identify students' perceptions of major distractions in the classroom based on seventeen internally (self-produced) and twenty-four externally produced classroom situations. METHODS: The students participating in this study rated the degree to which each distraction interferes with their concentration on the class materials and their ability to learn. Data were collected through surveys of 265 students (66 and 199 students from medical and basic classes, respectively), including 97 females and 168 males 17-23 years of age from the academic years 2010 to 2014. A validated self-administered questionnaire was handed to the students in the classroom. The students were asked to report and rate the classroom distraction produced by 24 external internal distracters (Table-II), on a 5-point scale. RESULTS: The results revealed that ringing cell phones in the class were the most commonly reported electronic external distractor for 68% of students, and 21% of them reported being extremely distracted by this noise. Having an instructor who is difficult to understand was the most commonly reported external behavioral distractor for 75% of students, and 48% of them rated this as extremely distracting. Students talking in class were the most self-produced distractor for 72% of students; negatively impacting their concentration and ability to learn, and 42% of them rated it as an extreme distractor. Wearing clothing with unusual words, drinking and eating in the classroom were minimally distracting colleagues. Overall, distractions (internal and external) were more significant for fifth-year students than the other years at a p-value < 0.001. CONCLUSION: Students believed that laptop and cell phone use in the classroom can effect their concentration and ability to learn. The students also felt that inappropriate behavior is a major distraction for students as well, and thus necessitates monitoring and improvement.

Pseudohypoaldosteronism in a Neonate Presenting as Life-Threatening Hyperkalemia.

Context. Pseudohypoaldosteronism type 1 (PHA1) is a life-threatening disease that causes severe hyperkalemia and cardiac arrest if not treated appropriately or if diagnosis is missed. Objective. To report a case of a newborn with vomiting and lethargy, ultimately diagnosed with pseudohypoaldosteronism. Patient. This case presented to the ED at an age of 14 days in hypovolemic shock. There was a family history of sudden infant death, her sister who was diagnosed with CAH and passed away at 3 months of age despite regular hormone replacement. Our patient had cardiac arrest in ED, due to hyperkalemia; while receiving fluid boluses, cardiopulmonary resuscitation was initiated. After stabilization, diagnostic workup demonstrated persistently low sodium, acidosis, and high potassium, which required peritoneal dialysis. Based on these findings, the patient was diagnosed with CAH. It turned out later that the patient had PHA1. Two years later, the patient had a new sibling with the same disease diagnosed at birth and started immediately on treatment without any complication. Conclusions and Outcome. This case highlights the significant diagnostic and therapeutic challenges in treating children with PHA1. Adrenal crisis is not always CAH; delayed diagnosis can lead to complication and even death. The presence of high plasma renin activity, aldosterone, and cortisol, along with the presence of hyponatremia and hyperkalemia, established the diagnosis of PHA type 1 and ruled out CAH.

Prevalence and characteristics of celiac disease in type I diabetes mellitus in Saudi Arabia.

OBJECTIVE: To examine the prevalence of celiac disease in young patients in the Kingdom of Saudi Arabia with type I diabetes mellitus. METHODS: Serum gliadin immunoglobulin (Ig) A and reticulin IgA antibody determination was performed in 123 patients with type I diabetes mellitus attending the pediatric diabetic clinic at King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia between 1995 and 1996. RESULTS: Elevated serum gliadin and reticulin IgA antibodies were found in the sera of 10 (8.1%) of the 123 diabetic children; none had gastrointestinal symptoms. Six of the 10 subjects had jejunal biopsy, which showed total villus atrophy. Four subjects did not undergo jejunal biopsy. The gender ratio of the biopsy positive is 5 male:1 female. All subjects with IgA positive were put on gluten free diet and normalized in a few months. CONCLUSION: The maximum prevalence of celiac disease in our population was 8.1% based on immunological marker and the minimum was 4.9% based on antibodies and biopsy results.