Clinical and molecular characterization of familial chylomicronemia in Saudi patients: a retrospective study

IntroductionFamilial chylomicronemia syndrome (FCS) is a severe type of hypertriglyceridemia (HTG). Despite its rarity, we have encountered more than 100 patients with FCS at our center. Therefore, we aimed to provide a useful resource for clinicians who may encounter such patients and help the scientific community accumulate knowledge to manage this disease.MethodsThis retrospective study described the clinical characteristics and management of FCS patients at (King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia).ResultsIn total, 29 pediatric patients were included, with a median age of 2.2 months [IQR: 1.3, 12]. Males predominated (62.0%). Key symptoms included a milky blood sample (72.4%), a family history of HTG (65.5%), hepatosplenomegaly (44.8%), acute pancreatitis (31.0%), and eruptive xanthoma (13.8%). Gemfibrozil (22 patients) reduced TG from 47.6 ± 55.7 to 9.4 ± 7.5 mmol/L (mean reduction 38.2 ± 54.5 mmol/L, P<0.001). Fenofibrate (19 patients) lowered TG from 45.4 ± 56.4 to 18.4 ± 13.1 mmol/L (mean difference 27.1 ± 52.0 mmol/L, P=0.001). While the Niacin-aspirin (4 patients) and diet alone (4 patients) had no significant effect (P=1.000) and (P=0.125), respectively.DiscussionThe rarity of FCS makes it more challenging for scientists and clinicians to achieve advancements in its management. We observed that anti-TG medications, especially fibrate derivatives, can be used safely in pediatric patients. They displayed excellent ability to control TG levels in combination with diet restrictions, and treatment compliance was good. Among fibrate derivatives, gemfibrozil controlled TG levels better than fenofibrate, and neither drug had significant side effects

The role of digital health in growth hormone therapy: perspectives from Gulf Cooperation Council pediatric endocrinologists

BackgroundWith the increasing use of digital health tools patient-generated health data play a crucial role in clinical decision-making, particularly for monitoring treatment adherence. However, integrating data into routine practice remains challenging, especially for chronic conditions such as growth disorders requiring growth hormone therapy (GHT). Integrating these data is essential to improve treatment adherence and growth outcomes in pediatric patients on GHT.AimTo explore perspectives of pediatric endocrinologists in the Gulf Cooperation Council (GCC) region on patient-generated health data for improving GHT adherence and identified strategies for integrating such data into clinical practice.MethodsA participatory workshop was conducted on March 2, 2024, in Dubai, United Arab Emirates, using the nominal group technique. Twelve pediatric endocrinologists from the GCC region, one chairman, and two moderators participated in the session. The session centered on three clinical scenarios: GHT naïve (recently diagnosed), poorly adherent, and poor responders. Through two structured voting rounds, experts individually identified, discussed, and ranked the top five most relevant and useful patient-generated health data factors. The first round prioritized key factors, while the second round allowed participants to reassess and refine their selections to reach consensus. The final discussion focused on how identified factors could integrate into clinical practice.ResultsTwenty-two influencing factors were identified, representing the most relevant and useful types of patient-generated health data for integration into clinical practice. Top factors in the first ranking round included demographic data (21 points: age, income level, familiarity with technology); patient’s feelings about treatments and satisfaction (19 points); and social background (17 points: family support, insurance, caregiving responsibilities). Other considerations included reasons for missed injections and educational needs (15 points each). In the second round, social background (35 points) ranked highest, followed by injection context (34 points: timing, comfort, administration support) and patient’s feelings about treatments and satisfaction (30 points) emphasized motivational and emotional aspects of adherence.ConclusionThe study highlights the significant role of social background, injection contexts, and patient satisfaction as key patient-generated health data factors for pediatric endocrinologists in the GCC region. These findings highlight their potential integration into GHT workflows to enhance clinical decision-making

A Saudi child with Sphingosine Phosphate Lyase insufficiency syndrome

Background: Sphingosine Phosphate Lyase Insufficiency Syndrome SPLIS is a recently described condition, which is associated with loss of function mutations in SGPL1, encoding sphingosine-1-phosphate lyase. In 2017, several groups reported this novel childhood syndrome that featured a wide range of presentations including fetal hydrops, steroid-resistant nephrotic syndrome (SRNS), primary adrenal insufficiency (PAI), rapid or insidious neurological deterioration, immunodeficiency, acanthosis and endocrine abnormalities. Case Presentation: A 7-year-old boy was presented to us with primary adrenal insufficiency on hydrocortisone following pediatrics endocrinology at our hospital. Genetic testing identified a homozygous variant of sphingosine-1-phosphate lyase 1 (NM 003901: exon8: c.665G&amp;gt;A: p.R222Q). At the same time, he was found to have nephrotic syndrome, and renal function rapidly deteriorated. Biopsy of the right kidney showed focal segmental glomerulosclerosis with collapsing features and acute interstitial nephritis. Later, he received a living- related renal transplant. He is doing well after the transplant. Conclusion: Patients with primary adrenal insufficiency should be carefully followed to develop nephrotic syndrome features, and molecular testing is the key to the diagnosis of the underlying etiology. This is the first reported case with sphingosine-1-phosphate lyase 1 that underwent renal transplantation in our region.</jats:p

Congenital adrenal hyperplasia with maple syrup urine disease: an example of consanguinity impact

Background: Maple syrup urine disease (MSUD) is a rare autosomal recessive metabolically inherited disorder, caused by an abnormal function of the branched-chain &#945;-keto acid dehydrogenase complex in the mitochondria. Case Presentation: The proband was born after a full-term pregnancy and normal vaginal delivery, with a good Apgar score (8, 9 at 1 and 5 minutes) and the birth weight of 2.5 kg with ambiguous genitalia in the form of phallus-like structure (3 cm), the fusion of labio-scrotal folds and urogenital sinus. The third day after birth, the proband was lethargic and developed hyperkalemia and hyponatremia, which required intravenous fluid therapy and hormonal replacement with hydrocortisone and fludrocortisone. The treatment was based on the positive family history of congenital adrenal hyperplasia in an older male sibling. Laboratory tests, cytogenetic study, tandem mass spectroscopy, and surgery were performed for the affected individual (II-8) using standard procedures. The laboratory and the treatment revealed significant improvements. Follow-up tandem mass spectroscopy results were observed in the normal range. The affected individual was treated with prednisone (2.5 mg bid) and Florinef (Fludrocortisone) (0.1 mg OD). The subject had regular menses, while acne and hirsutism were not observed. Conclusion: We are reporting the first case of MSUD associated with CAH, 21-hydroxylase deficiency salt-losing type and suggest that glucocorticoids might have an important role in treating MSUD cases. [JBCGenetics 2019; 2(2.000): 151-155

Coexistence of endocrinopathies in children with rheumatic diseases

AbstractBackground and objectivesTo examine the frequency of endocrinopathies in children with systemic lupus erythematosus (SLE) and juvenile idiopathic arthritis (JIA).Design and settingA cross-sectional study.Patients and methodsA study was conducted in Saudi children with SLE and JIA who were seen at King Faisal Specialist Hospital and Research Centre, Riyadh, between September 2013 and April 2015. All enrolled patients completed the clinical evaluation, which included information about family history of autoimmune disease, growth parameters and tanner stage, as well as the following assessments: vitamin D profile (parathyroid hormone and 25-OH vitamin D levels), TSH, FT4 and total T3, thyroglobulin antibodies, thyroperoxidase antibodies, random blood sugar, HbA1C, IGF1, IGFBP-3, LH, and FSH.ResultsA total of 42 patients, 22 with JIA and 20 with SLE, were included in the study. The mean participant age was 12.2 ± 5.3 years with a mean disease duration of 3.2 ± 3.4 years. Female gender was predominant (17 SLE, 13 JIA) in the patient population. Fifteen patients (35.7%) presented with a family history of autoimmune disease. The most frequently detected endocrinopathies were vitamin D insufficiency (35%) and thyroid disease (31%). Eight JIA patients and 7 SLE patients exhibited low vitamin D levels; 10 patients presented with hyperparathyroidism. Thyroid dysfunction was observed in 13 patients (8 SLE, 5 JIA), and 2 patients were found to be euthyroid (normal TSH, FT4) with positive thyroid autoantibodies. Furthermore, 7 patients presented with subclinical hypothyroidism (high TSH, normal FT4), and 4 patients presented with overt hypothyroidism (high TSH, low FT4). Seven patients (4 SLE and 3 JIA) presented with short stature due to growth hormone insufficiency (low IGF1, IGFBP-3). Two patients exhibited delayed puberty accompanied by low LH levels. Diabetes mellitus was more frequently observed in patients with JIA (4 patients) than in patients with SLE (1 patient).ConclusionOur findings demonstrated that coexistence of endocrinopathies is not uncommon in children diagnosed with JIA and SLE. Abnormal thyroid function occurs frequently and at a similar rate in children diagnosed with SLE and JIA. Thus, screening for endocrinopathies, namely thyroid disease, during the assessment of childhood SLE and JIA is worth consideration

A Saudi child with Sphingosine Phosphate Lyase insufficiency syndrome

Background: Sphingosine Phosphate Lyase Insufficiency Syndrome SPLIS is a recently described condition, which is associated with loss of function mutations in SGPL1, encoding sphingosine-1-phosphate lyase. In 2017, several groups reported this novel childhood syndrome that featured a wide range of presentations including fetal hydrops, steroid-resistant nephrotic syndrome (SRNS), primary adrenal insufficiency (PAI), rapid or insidious neurological deterioration, immunodeficiency, acanthosis and endocrine abnormalities. Case Presentation: A 7-year-old boy was presented to us with primary adrenal insufficiency on hydrocortisone following pediatrics endocrinology at our hospital. Genetic testing identified a homozygous variant of sphingosine-1-phosphate lyase 1 (NM 003901: exon8: c.665G&gt;A: p.R222Q). At the same time, he was found to have nephrotic syndrome, and renal function rapidly deteriorated. Biopsy of the right kidney showed focal segmental glomerulosclerosis with collapsing features and acute interstitial nephritis. Later, he received a living- related renal transplant. He is doing well after the transplant. Conclusion: Patients with primary adrenal insufficiency should be carefully followed to develop nephrotic syndrome features, and molecular testing is the key to the diagnosis of the underlying etiology. This is the first reported case with sphingosine-1-phosphate lyase 1 that underwent renal transplantation in our region. [JBCGenetics 2021; 4(1.000): 48-50

Graves’ disease thyroid dermopathy: a case report

Abstract Background Graves’ disease is the autoimmune activation of the thyroid gland causing diffuse enlargement and hyperfunction of the gland. Manifestations of Graves’ disease are multisystemic and include thyroid orbitopathy; pretibial myxedema, also referred to as thyroid dermopathy; and thyroid acropachy, described as a severe form of thyroid dermopathy. Our paper focuses on an atypical case of thyroid dermopathy. Case presentation An 11-year-old Saudi male presented with a prominent diffuse goiter and exophthalmos. Investigations were consistent with a diagnosis of Graves’ disease. The physical exam showed diffuse, non-pitting swelling of the ankle and penis, mimicking a lymphatic malformation. Further, multiple nodules were found on the hands and feet. Treatment of the nodules with cautery resulted in more severe nodules. Conclusion This report describes rare presentations of thyroid dermopathy mimicking lymphatic malformation. The Koebner phenomenon can explain this patient’s atypical presentations. Intralesional injections of triamcinolone and total thyroidectomy showed clear improvement

Genetics of Primary Adrenal Insufficiency Beyond CAH in Saudi Arabian Population

ABSTRACT Background The use of exome sequencing (ES) has helped in detecting many variants and genes that cause primary adrenal insufficiency (PAI). The diagnosis of PAI is difficult and can be life‐threatening if not treated urgently. Consanguinity can impact the detection of recessively inherited genes. Here, we report families with PAI in a consanguineous population of Saudi Arabia. Materials and Methods A cohort of 47 PAI patients (41 males and six females) representing 30 families was recruited. The cohort excluded congenital adrenal hyperplasia (CAH) cases and had a known consanguinity of 70%. Using ES, molecular genetic causes of PAI were investigated. Results In 30 unrelated families with PAI, pathogenic/likely pathogenic variants were detected in 27 families with a diagnostic yield of (90%). Clinically associated variants of uncertain significance (VUS) were identified in a further two PAI families (7%). Hemizygous variants in ABCD1 were the most common cause of PAI in this cohort (16 families) leading to adrenoleukodystrophy. A total of six novel variants were detected, of which four were predicted to be pathogenic (P) / likely pathogenic (LP) and two were VUS. Four pathogenic variants in ABCD1, NR0B1, and MC2R were detected in 10 families suggesting founder mutations. Conclusion In this cohort, ES detected a diagnostic molecular abnormality in 90% of patients with PAI phenotypes. X‐linked inheritance is the most common cause of PAI and founder mutations likely contributed to a high diagnostic yield