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Recessive congenital methemoglobinemia type II is a very rare autosomal recessive hematologic disorder due to NADH-cytochrome b5 reductase deficiency, usually caused by full-stop mutations or deletions. This disease classically presents with mild neonatal cyanosis, early onset severe progressive developmental delay, movement disorders, and progressive microcephaly. We report two siblings with recessive congenital methemoglobinemia type II whose evaluation revealed a novel p.Arg92Trp missense mutation of the CYB5R3 gene and a peculiar imaging finding of basal ganglia hypoplasia. Brain magnetic resonance imaging was performed at age 10 months in the older sibling and at age three months in the younger sibling. It revealed similar findings of bilateral small size of the lentiform and caudate nuclei and reduced frontotemporal brain volume. Our patient cases highlight that basal ganglia hypoplasia is an interesting clue to the very rare and frequently unsuspected diagnosis of recessive congenital methemoglobinemia type II, that may explain the associated movement disorders. The novel missense mutation is one of very few identified missense mutations known to cause severe type II recessive congenital methemoglobinemia.

Methemoglobinemia occurs when the heme moiety of hemoglobin (Hb) is oxidized from the ferrous to ferric state, leading to impairments in oxygen transport and delivery. Methemoglobinemia is rare in pediatric patients but has been described in the setting of congenital abnormalities in the Hb structure, inherited enzyme deficiencies, oxidative Hb injury in response to illness, and oxidative Hb injury due to toxicants. We present a 1-week-old infant born with a cervical lymphangioma who developed persistent desaturations that were unresponsive to oxygen after sclerotherapy with doxycycline. Arterial blood gas revealed a high Pao 2 despite low saturations being found on pulse oximetry and a methemoglobin level that was found to be elevated. Further sclerotherapy was discontinued, the saturations eventually normalized, and the methemoglobin level decreased. This is a novel report of sclerotherapy with doxycycline associated with the development of methemoglobinemia., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2019 by the American Academy of Pediatrics.)

Benzocaine (ethyl aminobenzoate), a topical anesthetic widely used before transesophageal echocardiography, has been reported to cause acquired methemoglobinemia. The incidence of benzocaine-induced methemoglobinemia in clinical practice, however, has been difficult to estimate. After systematic review of our institutional experience for clinically recognized cases of benzocaine-induced methemoglobinemia in patients undergoing transesophageal echocardiography, we report an estimated incidence of 0.115% (95% confidence interval 0.037-0.269). This report also provides the largest analysis of the incidence of methemoglobinemia in readministration cases. Although controversy remains as to whether this is an idiosyncratic versus dose-related response, a description of purported patient risk factors is included.