Lipoid Congenital Adrenal Hyperplasia With a Novel StAR Gene Mutation.

Lipoid congenital adrenal hyperplasia (LCAH) is characterized by disturbance of adrenal and gonadal steroidogenesis (OMIM:201710). It is caused by mutation in the Steroidogenic Acute Regulatory Protein (StAR). We report a classic case of LCAH in a neonate (46, XY) with phenotypic female genitalia who presented with significant salt loss with a novel homozygous variant mutation c.745-1G>C p. in StAR gene.

Novel Melano-Cortin-2-Receptor Gene Mutation Presenting With Infantile Cholestasis: A Case Report.

Introduction: For many years, congenital panhypopituitarism has been recognized to cause infantile cholestasis. However, the isolated cortisol deficiency as a cause of cholestasis and liver failure was rarely reported. Case description: A 32-days old male infant presented to the hepatology clinic with infantile cholestasis. His initial workup revealed alanine transaminase (ALT) level of 138 U/L, aspartate transaminase level of 76 U/L, total bilirubin (T.Bil) of 103 mmol/L, direct bilirubin of (D.Bil) 83 mmol/L, gamma-glutamyl transpeptidase (GGT) level of 28 U/L with normal prothrombin time (PT) of 13 seconds. One week later, the patient developed severe bronchiolitis necessitating mechanical ventilation associated with acute liver failure and worsening cholestasis. His ALT increased to 303.5 U/L and direct bilirubin increased to 204 mmol/L with prolongation of PT to 18.9 seconds reflecting derangement in synthetic liver functions. There was associated hypoglycemia, hyponatremia and high normal potassium level with a picture of adrenal insufficiency. Hormonal workup and genetic testing revealed isolated cortisol deficiency with a novel homozygous mutation c.763_764delAT (p. Met255ValfsX17) in Melanocortin 2 receptor gene (MC2R) and the patient was diagnosed as familial primary glucocorticoid deficiency. The patient was maintained on cortisol replacement therapy with the resolution of cholestasis and normalization of liver functions. Conclusions: Patients presenting with infantile cholestasis associated with documented hypoglycemia should alert pediatricians about the possibility of familial glucocorticoid deficiency and prompt investigation of adrenal function should be considered. Cortisol replacement therapy leads to the resolution of cholestasis.

The Impact of COVID-19 Pandemic Lockdown on the Incidence of New-Onset Type 1 Diabetes and Ketoacidosis Among Saudi Children.

Background: Overburdened healthcare systems during the coronavirus disease (COVID-19) pandemic led to suboptimal chronic disease management, including that of pediatric type 1 diabetes mellitus (T1DM). The pandemic also caused delayed detection of new-onset diabetes in children; this increased the risk and severity of diabetic ketoacidosis (DKA). We therefore investigated the frequency of new-onset pediatric T1DM and DKA in Saudi Arabia during the COVID-19 pandemic and compared it to the same period in 2019. Methods: We conducted a multicenter retrospective cohort study, including patients aged 1-14 years admitted with new-onset T1DM or DKA during the COVID-19 pandemic (March-June 2020) and the same period in 2019. We assessed factors including age, sex, anthropometric measures, nationality, duration of diabetes, diabetes management, HbA1c levels, glycemic control, cause of admission, blood gas levels, etiology of DKA, DKA complications, length of hospital stay, and COVID-19 test status. Result: During the lockdown, 106 children, compared with 154 in 2019, were admitted to 6 pediatric diabetes centers. Among the admissions, DKA was higher in 2020 than in 2019 (83% vs. 73%; P=0.05; risk ratio=1.15; 95% confidence interval, 1.04-1.26), after adjusting for age and sex. DKA frequency among new-onset T1DM and HbA1c levels at diagnosis were higher in 2020 than in 2019 (26% vs. 13.4% [P=<0.001] and 12.1 ± 0.2 vs. 10.8 ± 0.25 [P<0.001], respectively). Females and older patients had a higher risk of DKA. Conclusion: The lockdown implemented in Saudi Arabia has significantly impacted children with T1DM and led to an increased DKA frequency, including children with new-onset T1DM, potentially owing to delayed presentation.

Vici syndrome with pathogenic homozygous EPG5 gene mutation: A case report and literature review.

RATIONALE: Vici syndrome (VICIS) is a rare, autosomal recessive neurodevelopmental disorder with multisystem involvement characterized by agenesis of the corpus callosum, congenital cataracts, cardiomyopathy, combined immunodeficiency, significant developmental delay, and hypopigmentation and in some cases loss of hearing. It is caused by mutations in Ectopic P-granules protein 5 gene, which is responsible for regulating autophagy activity. PATIENT CONCERN: We report a 6-month-old Saudi female patient who was the second-born baby of first cousins. She was born by normal spontaneous vertex vaginal delivery. Parents noticed that she had global developmental delay and recurrent hospital admissions due to chest infections. DIAGNOSIS: Brain magnetic resonance imaging showed brain atrophy with corpus callosum agenesis. Ophthalmology examination revealed bilateral congenital cataract. Molecular genetic testing identified the pathogenic homozygous variant c.4751T>A p. (Leu1584*) on exon 27 of the EPG5 gene and confirmed the diagnosis of Vici syndrome. INTERVENTIONS: Supportive multidisciplinary care plan was initiated to this untreatable syndrome. OUTCOMES: The patient died at the age of 6 months due to sepsis with uncompensated septic shock. LESSONS: VICIS is a rare untreatable disorder with worldwide distribution. High index of suspicion is needed to diagnose it and family genetic counselling is crucial.

Sotos syndrome: A case report of 1st genetically proven case from Saudi Arabia with a novel mutation in NSD1 gene.

RATIONALE: Sotos syndrome is a rare genetic disorder characterized by rapid growth during infancy and childhood; ≥2 SD for height and head circumference; distinctive facial appearance and developmental delay.Ten clinically diagnosed cases have been reported from Saudi Arabia; none of them was genetically confirmed. PATIENT CONCERNS: A male Saudi patient, who had a birth length and head circumference above 97th centile, presented with abnormal rapid growth, delayed motor and mental milestones, aggressive behavior, obsession to close doors, nail biting, defective attention, and hyperactivity. DIAGNOSES: Sotos syndrome was suspected INTERVENTIONS:: Molecular genetic analysis for NSD1 gene was carried for the patient. OUTCOMES: A novel heterozygous deletion of all exons 1 to 23 of the NSD1 gene was detected. Genetic counseling was carried for the family with extended genetic testing for the parents and his siblings with normal results. LESSONS: Despite its worldwide distribution, Sotos syndrome may be under-reported. Besides its characteristic clinical picture, molecular genetic testing is also extremely recommended.

Late presentation of necrotizing enterocolitis associated with rotavirus infection in a term infant with hyperinsulinism on octreotide therapy: A case report.

RATIONALE: Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycemia in infancy that can cause permanent brain damage. Consequently, optimal management is extremely important. Current pharmacologic and surgical treatment were available that included diazoxide and octreotides. PATIENT CONCERNS: A 4 month old Saudi male patient diagnosed at our hospital as CHI, treated with near total pancreatectomy and octreotide therapy of 30 mcg/kg/day presented with severe abdominal distension, vomiting and bloody diarrhea. DIAGNOSES: The patient was diagnosed as necrotising enterocolitis (NEC) associated with Rota virus infection which played together with octeriotides as risk factors for NEC. INTERVENTIONS: Radiological investigations and multidisciplinary team management with endocrinologist, neonatologist, pediatric surgeon, and gastroenterologist. OUTCOMES: Resolution of NEC with conservative medical management and was discharged after 1 month of hospital stay with follow up with all concerned sub specialties. LESSONS: NEC can develop in patients treated with octreotides especially when associated with another risk factor such as rotavirus infection.

Idiopathic hypoparathyroidism with extensive intracranial calcification in children: First report from Saudi Arabia.

RATIONALE: Pediatric idiopathic hypoparathyroidism with extensive intracranial calcifications outside the basal ganglia (BG) is extremely rare with less than 10 cases worldwide. PATIENT CONCERNS: An 11-year-old Saudi male child presented with tetany with otherwise normal neurological and other body system examination diagnoses severe hypocalcemia for differential diagnosis. INTERVENTIONS: Further investigations revealed hyperphosphatemia and undetectable serum intact parathyroid hormone. Brain computed tomography revealed BG and extensive brain calcifications. He has no dysmorphic features, vitiligo, mucocuataneous manifestations, or hair loss. He had normal hemoglobin, electroencephalogram, and skeletal survey, with negative autoantibodies to alpha and omega interferons and negative genetic testing for Glial Cell Missing 2 (GCM2) and calcium-sensing receptors (CaSRs) excluding known causes of hypoparathyroidism. OUTCOMES: This case presents a rare entity of idiopathic hypoparathyroidism with extensive intracranial calcification, not only in BG but also outside the extrapyramidal system with normal mentality, development, pubertal achievement, and neurological examination. To our knowledge, this is the first report from Saudi Arabia in pediatrics. LESSONS: Idiopathic hypoparathyroidism is a diagnosis of exclusion after ruling out all known causes of hypoparathyroidism. It is associated with BG calcifications, but extensive intracranial calcifications outside the BG are extremely rare.