Two Siblings with Familial Chylomicronemia Syndrome: Disease Course and Effectiveness of Early Treatment

There are no adequate data that evaluate the safety and effectiveness of lowering triglyceride levels in very young children. The authors report a family with two male siblings, 7 and 4 years old, affected by familial hyperchylomicronemia. The oldest was diagnosed at birth during evaluation of jaundice, and the youngest showed asymptomatic hypertriglyceridemia by 6 months of age. Due to high triglyceride levels, Gemfibrozil (a fibric acid derivative) was started at diagnosis. Close clinical followup and laboratory monitoring of these children showed no side effects from the drug, and the risk of acute pancreatitis was significantly reduced

Case Report Two Siblings with Familial Chylomicronemia Syndrome: Disease Course and Effectiveness of Early Treatment

There are no adequate data that evaluate the safety and effectiveness of lowering triglyceride levels in very young children. The authors report a family with two male siblings, 7 and 4 years old, affected by familial hyperchylomicronemia. The oldest was diagnosed at birth during evaluation of jaundice, and the youngest showed asymptomatic hypertriglyceridemia by 6 months of age. Due to high triglyceride levels, Gemfibrozil (a fibric acid derivative) was started at diagnosis. Close clinical followup and laboratory monitoring of these children showed no side effects from the drug, and the risk of acute pancreatitis was significantly reduced

A novel mutation in HSD11B2 causes apparent mineralocorticoid excess in an Omani kindred

Apparent mineralocorticoid excess (AME) is a rare autosomal recessive genetic disorder causing severe hypertension in childhood due to a deficiency of 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2), which is encoded by HSD11B2. Without treatment, chronic hypertension leads to early development of end-organ damage. Approximately 40 causative mutations in HSD11B2 have been identified in ∼100 AME patients worldwide. We have studied the clinical presentation, biochemical parameters, and molecular genetics in six patients from a consanguineous Omani family with AME. DNA sequence analysis of affected members of this family revealed homozygous c.799A>G mutations within exon 4 of HSD11B2, corresponding to a p.T267A mutation of 11βHSD2. The structural change and predicted consequences owing to the p.T267A mutation have been modeled in silico. We conclude that this novel mutation is responsible for AME in this family

Clinical, genetic, and structural basis of apparent mineralocorticoid excess due to 11β-hydroxysteroid dehydrogenase type 2 deficiency

Mutations in 11β-hydroxysteroid dehydrogenase type 2 gene (HSD11B2) cause an extraordinarily rare autosomal recessive disorder, apparent mineralocorticoid excess (AME). AME is a form of low renin hypertension that is potentially fatal if untreated. Mutations in the HSD11B2 gene result either in severe AME or a milder phenotype (type 2 AME). To date, ∼40 causative mutations have been identified. As part of the International Consortium for Rare Steroid Disorders, we have diagnosed and followed the largest single worldwide cohort of 36 AME patients. Here, we present the genotype and clinical phenotype of these patients, prominently from consanguineous marriages in the Middle East, who display profound hypertension and hypokalemic alkalosis. To correlate mutations with phenotypic severity, we constructed a computational model of the HSD11B2 protein. Having used a similar strategy for the in silico evaluation of 150 mutations of CYP21A2, the disease-causing gene in congenital adrenal hyperplasia, we now provide a full structural explanation for the clinical severity of AME resulting from each known HSD11B2 missense mutation. We find that mutations that allow the formation of an inactive dimer, alter substrate/coenzyme binding, or impair structural stability of HSD11B2 yield severe AME. In contrast, mutations that cause an indirect disruption of substrate binding or mildly alter intramolecular interactions result in type 2 AME. A simple in silico evaluation of novel missense mutations could help predict the often-diverse phenotypes of an extremely rare monogenic disorder

Newborn with Dilated Cardiomyopathy Secondary to Vitamin D Deficiency

Hypocalcemia is a rare but reversible cause of dilated cardiomyopathy with limited cases being reported in the literature. Vitamin D deficiency is the main cause of hypocalcemia in almost all reported cases. We report a newborn presented with hypocalcemia-induced dilated cardiomyopathy secondary to vitamin D deficiency. After calcium and vitamin D therapy, the baby showed a rapid recovery of the cardiac function

A Novel Mutation Causing 17-β-Hydroxysteroid Dehydrogenase Type 3 Deficiency in an Omani Child: First Case Report and Review of Literature

This is the first case report in Oman and the Gulf region of a 17-β-hydroxysteroid dehydrogenase type 3 (17-β-HSD3) deficiency with a novel mutation in the HSD17B3 gene that has not been previously described in the medical literature. An Omani child was diagnosed with 17-β-HSD3 deficiency and was followed up for 11 years at the Pediatric Endocrinology Clinic, Royal Hospital, Oman. He presented at the age of six weeks with ambiguous genitalia, stretched penile and bilateral undescended testes. Ultrasound showed no evidence of any uterine or ovarian structures with oval shaped solid structures in both inguinal regions that were confirmed by histology to be testicular tissues with immature seminiferous tubules only. The diagnosis was made by demonstrating low serum testosterone and high androstenedione, estrone, and androstenedione:testosterone ratio. Karyotyping confirmed 46,XY and the infant was raised as male. Testosterone injections (25mg once monthly) were given at two and six months and then three months before his surgeries at five and seven years of age when he underwent multiple operations for orchidopexy and hypospadias correction. At the age of 10 years he developed bilateral gynecomastia (stage 4). Laboratory investigations showed raised follicle-stimulating hormone, luteinizing hormone, androstenedione, and estrone with low-normal testosterone and low androstendiol glucurunide. Testosterone injections (50mg once monthly for six months) were given that resulted in significant reduction in his gynecomastia. Molecular analysis revealed a previously unreported homozygous variant in exon eight of the HSD17B3 gene (NM_000197.1:c.576G>A.Trp192*). This variant creates a premature stop codon, which is very likely to result in a truncated protein or loss of protein production. This is the first report in the medical literature of this novel HSD17B3 gene mutation. A literature review was conducted to identify the previous studies related to this disorder