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.

Clinical characteristics and phenotype-genotype review of 25 Omani children with congenital hyperinsulinism in infancy. A one-decade single-center experience.

OBJECTIVES: To report the genotype-phenotype characteristics, demographic features and clinical outcome of Omani patients with congenital hyperinsulinism (CHI). Methods: We retrospectively analyzed the clinical, biochemical, genotypical, phenotypical characteristics and outcomes of  children with CHI who were presented to the pediatric endocrine team in the Royal Hospital, Muscat, Oman between January 2007 and December 2016. Results: Analysis of 25 patients with CHI genetically revealed homozygous mutation in ABCC8 in 23 (92%) patients and 2 patients (8%) with compound heterozygous mutation in ABCC8. Fifteen (60%) patients underwent subtotal pancreatectomy as medical therapy failed and 2 (8%) patients showed response to medical therapy. Three patients expired during the neonatal period, 2 had cardiomyopathy and sepsis, and one had sepsis and severe metabolic acidosis. Out of the 15 patients who underwent pancreatectomy, 6 developed diabetes mellitus, 6 continued to have hypoglycemia and required medical therapy and one had pancreatic exocrine dysfunction post-pancreatectomy, following up with gastroenterology clinic and was placed on pancreatic enzyme supplements, while 2 patients continued to have hypoglycemia and both had abdominal MRI and 18-F-fluoro-L-DOPA positron emission tomography scan (PET-scan), that showed  persistent of the disease and started on medical therapy. Conclusion:  Mutation in ABCC8 is the most common cause of CHI and reflects the early age of presentation. There is a need for early diagnosis and appropriate therapeutic strategy.