Optimal lysosome function requires maintenance of an acidic pH maintained by proton pumps in combination with a counterion transporter such as the Cl À /H þ exchanger, CLCN7 (ClC-7), encoded by CLCN7. The role of ClC-7 in maintaining lysosomal pH has been controversial. In this paper, we performed clinical and genetic evaluations of two children of different ethnicities. Both children had delayed myelination and development, organomegaly, and hypopigmentation, but neither had osteopetrosis. Whole-exome and-genome sequencing revealed a de novo c.2144A>G variant in CLCN7 in both affected children. This p.Tyr715Cys variant, located in the C-terminal domain of ClC-7, resulted in increased outward currents when it was heterologously expressed in Xenopus oocytes. Fibroblasts from probands displayed a lysosomal pH approximately 0.2 units lower than that of control cells, and treatment with chloroquine normalized the pH. Primary fibroblasts from both probands also exhibited markedly enlarged intracellular vacuoles; this finding was recapitulated by the overexpression of human p.Tyr715Cys CLCN7 in control fibroblasts, reflecting the dominant, gain-of-function nature of the variant. A mouse harboring the knock-in Clcn7 variant exhibited hypopigmentation, hepatomegaly resulting from abnormal storage, and enlarged vacuoles in cultured fibroblasts. Our results show that p.Tyr715Cys is a gain-of-function CLCN7 variant associated with developmental delay, organomegaly, and hypopigmentation resulting from lysosomal hyperacidity, abnormal storage, and enlarged intracellular vacuoles. Our data supports the hypothesis that the ClC-7 antiporter plays a critical role in maintaining lysosomal pH.

About half the cases of energy drink-related toxicity involved unintentional exposures by children < 6 years old. Educational campaigns and legal restrictions on the sale of energy drinks were associated with decreasing calls to poison centers for energy drink toxicity and are encouraged.

Patient now 19 years old has intellectual disability, developmental delay, absent speech, seizures, hypotonia, severe motor disability (non-ambulatory), short stature, relative macrocephaly. Patient uses gastric tube for feeding and has gastroesophageal reflux. Facial dysmorphisms include short palpebral fissures, large incisors, full eyebrows. Fingers are short and trident-shaped.Brain MRI revealed progressive cerebral and cerebellar volume loss, hypodensity in the left basal ganglia, unchanged and consistent with a lacune infarct (remote). There is a less conspicuous area of hypodensity on the contralateral side. There are hypodense white matter changes along the periventricular white matter and bilateral centrum semiovale.

Drowning is a leading cause of injury-related death in children. In 2017, drowning claimed the lives of almost 1000 US children younger than 20 years. A number of strategies are available to prevent these tragedies. As educators and advocates, pediatricians can play an important role in the prevention of drowning. BACKGROUND Drowning is the leading cause of injury death in US children 1 to 4 years of age and the third leading cause of unintentional injury death among US children and adolescents 5 to 19 years of age. 1 In 2017, drowning claimed the lives of almost 1000 US children. Fortunately, childhood unintentional drowning fatality rates have decreased steadily from 2.68 per 100 000 in 1985 to 1.11 per 100 000 in 2017. Rates of drowning death vary with age, sex, and race and/or ethnicity, with toddlers and male adolescents at highest risk. After 1 year of age, male children of all ages are at greater risk of drowning than female children. Overall, African American children have the highest drowning fatality rates, followed in order by American Indian and/or Alaskan native, white, Asian American and/or Pacific Islander, and Hispanic children. For the period 2013-2017, the highest drowning death rates were seen in white male children 0 to 4 years of age (3.44 per 100 000), American Indian and/or Alaskan native children 0 through 4 years (3.58), and African American male adolescents 15 to 19 years of age (4.06 per 100 000). 1 Drowning is also a significant source of morbidity for children. In 2017, an estimated 8700 children younger than 20 years of age visited a hospital emergency department for a drowning event, and 25% of those children were hospitalized or transferred for further care. 1 Most victims of nonfatal drowning recover fully with no neurologic deficits, but severe long-term neurologic deficits are seen with extended submersion times (.6 minutes), prolonged resuscitation efforts, and lack of early bystander-initiated cardiopulmonary resuscitation (CPR). 2-4 The American Academy of Pediatrics issues this revised policy statement because of new information and research regarding (1) populations at