Context:Patients with congenital adrenal hyperplasia (CAH) often suffer from long-term complications secondary to chronic glucocorticoid therapy and suboptimal treatment regimens.Objective: The aim of the study was to describe clinical characteristics of a large cohort of pediatric and adult CAH patients. Design and Setting:We conducted a cross-sectional study of 244 CAH patients [183 classic, 61 nonclassic (NC)] included in a Natural History Study at the National Institutes of Health. Main Outcome Measure(s):Outcome variables of interest were height SD score, obesity, hypertensive blood pressure (BP), insulin resistance, metabolic syndrome, bone mineral density, hirsutism (females), and testicular adrenal rest (TART). Results:The majority had elevated or suppressed androgens, with varied treatment regimens. Mean adult height SD score was Ϫ1.0 Ϯ 1.1 for classic vs. Ϫ0.4 Ϯ 0.9 for NC patients (P ϭ 0.015). Obesity was present in approximately one third of patients, across phenotypes. Elevated BP was more common in classic than NC patients (P Յ 0.01); pediatric hypertensive BP was associated with suppressed plasma renin activity (P ϭ 0.001). Insulin resistance was common in classic children (27%) and adults (38% classic, 20% NC); 18% of adults had metabolic syndrome. The majority (61%) had low vitamin D; 37% of adults had low bone mineral density. Hirsutism was common (32% classic; 59% NC women). TART was found in classic males (33% boys; 44% men). There is a wide spectrum of phenotypes determined by the residual 21-hydroxylase activity, with a continuum between the classic or severe form and the mild nonclassic (NC) form. The incidence of classic CAH ranges from 1 in 10,000 to 20,000 live births worldwide and is subclassified into salt-wasting (SW) and simple virilizing (SV), re- Conclusions

Clinical evaluation for connective tissue dysplasia should be routinely performed in CAH patients, especially those harboring a CYP21A2 deletion.

Background Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is an autosomal recessive disorder of cortisol biosynthesis caused by CYP21A2 mutations. An increase in gene copy number variation (CNV) exists at the CYP21A2 locus. CNV of C4, a neighboring gene that encodes complement component 4, is associated with autoimmune disease susceptibility. Methods Comprehensive genetic analysis of the RCCX (RP-C4-CYP21-TNX) region was conducted in 127 unrelated 21-OHD patients (100 classic, 27 nonclassic). C4 copy number was determined by Southern blot. C4 CNV and serum C4 levels were evaluated in relation to CYP21A2 mutations and relevant phenotypes. Results The most common CYP21A2 mutation associated with the nonclassic form of CAH, V281L, was associated with high C4 copy number (p=7.13×10−16). Large CYP21A2 deletion was associated with low C4 copy number (p=1.61×10−14). Monomodular RCCX with a short C4 gene, a risk factor for autoimmune disease, was significantly less frequent in CAH patients compared to population estimates (2.8 vs. 10.6%; p=1.08×10−4). Conclusions CAH patients have increased C4 CNV, with mutation-specific associations that may be protective for autoimmune disease. The study of CYP21A2 in relation to neighboring genes provides insight into the genetics of CNV hotspots, an important determinant of human health.

Although the prognosis of neonatal herpes simplex virus (HSV) infection has improved with intravenous acyclovir, the morbidity and mortality of disseminated disease remains high. Transaminitis and thrombocytopenia have been reported to be sensitive markers of neonatal HSV disease; however, early diagnosis remains a challenge due to a lack of specific clinical and laboratory indicators for this disease process. Ferritin, an acute phase reactant known for its use in diagnosing hemophagocytic lymphohistiocytosis, has recently been reported as extremely elevated in neonates with disseminated HSV due to its high inflammatory nature. We report three cases of neonates at a single institution with hyperferritinemia in the setting of disseminated HSV. Based on this case series, we discuss whether ferritin can be used as an early diagnostic marker in the setting of suspected neonatal HSV disease. [ Pediatric Annals . 2021;50(6):e264–e267.]

Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a well-recognized complication of allogeneic and autologous hematopoietic cell transplantation (HCT). The diagnosis and treatment of VOD/SOS require the involvement of multiple specialists covering a wide range of expertise. Interprofessional team-based medical care is standard practice for patients undergoing HCT and has been shown to improve patient and provider satisfaction, enhance efficiency, and improve patient outcomes, particularly for patients in complex medical situations like those with VOD/SOS post-HCT. Interdisciplinary team-based models focus on the synthesis and harmonization of knowledge and methods from different disciplines to create an integrative approach to patient care that both maximizes the expertise of each involved specialist and encourages thought beyond each specialist’s discipline. Multidisciplinary team members provide additive support and work collaboratively with the core team to provide knowledge from their field. The composition of the interdisciplinary HCT team should center on the needs of the patient and institutional resources and involve the expertise of additional multidisciplinary team members based on clinical needs. This review focuses on interdisciplinary and multidisciplinary team-based care of patients with VOD/SOS post-HCT and provides an example of a collaborative VOD/SOS team that includes transplant physicians, nurses, pharmacists, nutrition/dietary specialists, and intensive care teams.