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Autism spectrum disorder (ASD) is the most common disability-causing neurodevelopmental disorder in childhood. Although inborn errors of metabolism (IEM) are rare causes of ASD, they are significant for several reasons, including implications in genetic counseling and determination of prognosis. In this article, we present a 6-year-old boy who presented to us with ASD and was diagnosed with creatine transporter deficiency. Physical and neurologic examination of this patient had not previously raised suspicion of IEM, but twin pregnancy, prematurity, NICU stay due to necrotizing enterocolitis, transient infantile hypotonia, gross-motor delay, breath-holding spells, and a single febrile seizure complicated the history. MRI revealed mild T2-hyperintensity in posterior periventricular white matter. Further evaluation with magnetic resonance spectroscopy, which showed a decreased creatine peak, led to diagnostic investigations for disorders of creatine metabolism, revealing increased urinary creatine:creatinine ratio and a de novo, novel hemizygous frameshift variant in SLC6A8 Clinicians are advised to maintain a high index of suspicion for IEM and to evaluate patients with ASD for syndromic features. Although current guidelines from relevant organizations differ in their recommendations regarding the necessity and the extent of metabolic screening in ASD, there is a growing trend toward screening for treatable IEM. In this case report, we present challenges and pitfalls in the diagnostic journey for creatine transporter deficiency and underline the significance of a thorough history and physical examination in the evaluation of a child with ASD., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)

Intravitreal bevacizumab therapy in preterm infants for retinopathy of prematurity (ROP) can be associated with hypotension. We report twin preterm infants who developed hypotension within 1 day after intravitreal bevacizumab therapy for ROP. Before receiving the medication, their clinical statuses were stable and similar. The dose, procedure, and premedication were the same; however, twin B presented with hypotension for 3 days. Although bevacizumab-related hypotension has been described in product information (incidence rate 7%-15%), this is the first case report of intravitreal bevacizumab for ROP inducing hypotension. Physicians should be aware of intravitreal bevacizumab therapy-related hypotension when treating ROP. We suggest conducting a postmarketing active surveillance on the systemic adverse effects of this regimen in preterm infants., (Copyright © 2016 by the American Academy of Pediatrics.)

Tuberous sclerosis complex (TSC) is a genetic disorder characterized by mammalian target of rapamycin (mTOR) activation and growth of benign tumors. Some TSC lesions, such as cardiac rhabdomyomas and cortical tubers in the brain, occur in fetuses, and some, such as renal angiomyolipomas (AMLs) and skin angiofibromas, develop over years. Recently, the mTOR inhibitor everolimus was shown to be effective in the treatment of subependymal giant cell astrocytomas (a brain tumor) and renal AMLs (kidney tumors) in TSC patients. We present monozygotic twin sisters affected with TSC. Since age 4 years, 1 of the sisters has been treated with everolimus; the other sister received no mTOR inhibitor treatment. After 24-month follow-up, everolimus treatment resulted in a significant brain tumor volume decrease in the treated twin. This child presents no facial angiofibroma, and no renal AMLs. The brain tumor in the nontreated sister is stable in size, but in the meantime, she has developed significant facial angiofibroma and renal AMLs. This observation indicates that early mTOR inhibition in TSC patients may prevent the development of TSC lesions and alter the natural history of the disease.

Persistently patent ductus arteriosus (PDA), affecting approximately one-third of all very low birth weight infants, can lead to significant morbidity and mortality. Recently, ibuprofen has been recommended over indomethacin to close PDAs because of a reduction in risk of necrotizing enterocolitis. Pulmonary hypertension is a rare but potentially fatal complication of ibuprofen administration in preterm infants. We report 2 infants who developed this complication after receiving therapeutic L-lysine ibuprofen preparation for the PDA closure. The first infant, 1 of twins weighing 640 g, was born at 24 weeks' gestation. The second infant, born at 26 weeks' gestation, was small for gestational age, weighing 439 g. In both cases, ibuprofen was initiated after echocardiographic confirmation of a moderate-sized to large PDA and an otherwise normal intracardiac anatomy. Both infants had echocardiographic evidence of increased pulmonary vascular resistance but shunting across the PDA was left to right. The infants deteriorated within 48 to 72 hours, and repeat echocardiograms revealed evidence of severe pulmonary hypertension. Both infants died of refractory hypotension and hypoxemia. When considering the use of ibuprofen therapy for PDA closure, clinicians should keep in mind the potential serious complication of pulmonary hypertension, even if a shunt across the PDA is left to right.