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.

Diagnosis and management of X-linked hypophosphatemia in children and adolescent in the Gulf Cooperation Council countries.

INTRODUCTION: X-linked hypophosphatemia (XLH) is a rare inherited cause of hypophosphatemic rickets and osteomalacia. It is caused by mutations in the phosphate-regulating endopeptidase homolog, X-linked (PHEX). This results in increased plasma fibroblast growth factor-23 (FGF23), which leads to loss of renal sodium-phosphate co-transporter expression leading to chronic renal phosphate excretion. It also leads to low serum 1,25-dihydroxyvitamin D (1,25(OH)2D), resulting in impaired intestinal phosphate absorption. Chronic hypophosphatemia in XLH leads to impaired endochondral mineralization of the growth plates of long bones with bony deformities. XLH in children and adolescents also causes impaired growth, myopathy, bone pain, and dental abscesses. XLH is the most frequent inherited cause of phosphopenic rickets/osteomalacia. Hypophosphatemia is also found in calcipenic rickets/osteomalacia as a result of secondary hyperparathyroidism. Thus, chronic hypophosphatemia is a common etiologic factor in all types of rickets. RESULTS: There is considerable overlap between symptoms and signs of phosphopenic and calcipenic rickets/osteomalacia. Wrong diagnosis leads to inappropriate treatment of rickets/osteomalacia. Nutritional rickets and osteomalacia are common in the Gulf Cooperation Council countries which include Saudi Arabia, United Arab Emirates, Kuwait, Qatar, Bahrain, and Oman. Due to high levels of consanguinity in the region, genetic causes of phosphopenic and calcipenic rickets/osteomalacia are also common. CONCLUSION: This guideline was developed to provide an approach to the diagnosis of XLH, especially where there is no family history of the disease, and that other related conditions are not mistaken for XLH. We also guide the medical management of XLH with conventional treatment and with burosumab, a recombinant human IgG1 monoclonal antibody to FGF23.

The prevalence, risk factors, and screening measure for prediabetes and diabetes among Emirati overweight/obese children and adolescents.

BACKGROUND: The aim of the study was to estimate the prevalence of prediabetes and type 2 diabetes (T2D) among overweight/obese children and adolescents using different diagnostic/screening methods in comparison. METHODS: We recruited overweight/obese Emirati students; grade 6-12 (age 11-17 years) from 16 government schools in Sharjah (UAE). Anthropometric, demographic, and clinical history data was measured by standard methods. Body mass index (BMI) was categorized according to BMI percentile charts for age and sex - CDC. Capillary fasting blood glucose (FBG) and glycated hemoglobin (HbA1c) were measured by finger prick test, followed by confirmatory oral glucose tolerance tests (OGTT) and venous HbA1c for students with abnormal capillary FBG and/or HbA1c. RESULTS: Of a total of 1034 participants (45 % females) median age 14.7 years, 443 (43 %) students had abnormal screening results. The prevalence of prediabetes and T2D was 5.4 % and 0.87 %, respectively, based on OGTT (gold standard). HbA1c showed a considerable discrepancy regarding the prevalence of prediabetes (21.9 %), but not diabetes. There was a statistically significant difference in the BMI Z-scores between the three different groups of students showing normal glycemic testing, prediabetes and T2D (p = 0.041). Univariate logistic regression analysis showed that glycemic status was significantly associated with family history of T2D first-degree relatives [OR 1.87: 95 % CI: 1.04-3.36; P = 0.036], parents employment [OR 1.79: 95 % CI: 1.06-3.02; P = 0.029] and levels of triglycerides [OR 2.28: 95 % CI: 1.11-4.68; P = 0.024]. CONCLUSIONS: The prevalence of prediabetes and diabetes was high among overweight/obese Emirati children and adolescents. The numbers for prediabetes were considerably higher when using HbA1c as compared to OGTT. Overall adiposity, family history of T2D, employment and high levels of triglycerides were risk factors associated with abnormal glycemic testing.