Case Presentation: A 27-year-old male without medical history presented with paresthesias in his hands and feet, and numbness and instability from his waist down for 4 days. The patient initially denied any illicit substances, had no dietary restrictions, and no known medical problems in the family. Cervical MRI revealed T2 dorsal column hypersensitivity consistent with subacute combined degeneration. Vitamin B12 was 215 pg/mL (normal: >200-400 pg/mL), methylmalonic acid (MMA) was 4872 nmol/L (normal: 70-270 nmol/L), and homocysteine was 69.4 μmol/L (normal: 3.7-13.9 μmol/L). Further history revealed the patient had been using inhaled nitrous oxide (NO) for at least 4 weeks, approximately three times daily. The patient received intramuscular B12 repletion and avoided NO with resolution of his symptoms.
Discussion: Vitamin B12 deficiency is a routine medical issue that can result from insufficient intake due to diet, or malabsorption. Common symptoms include paresthesias, gait problems, glossitis, macrocytic anemia, mood disturbances, and jaundice. A B12 level < 200 pg/mL confirms deficiency. For patients with a B12 between 200-400, an elevated MMA level is also confirmatory. This patient exhibited the typical signs of symptomatic B12 deficiency, but without obvious cause in his history to suggest either a dietary or malabsorption issue. The borderline low level of B12, coupled with the severely elevated level of MMA, confirmed the diagnosis. When history revealed chronic use of inhaled NO for recreational purposes, further investigation identified this habit as the potential cause of symptomatic B12 deficiency.Inhaled NO is used in many professional fields and has anesthetic and analgesic properties that can result in a state of euphoria. Popularity of recreational use of NO has increased due to ease of access in whipped cream canisters, among other sources. NO converts the monovalent cobalt ion in vitamin B12 to a bivalent form, preventing B12 from functioning as a carrier for the methyl group involved in transmethylation reactions. Methylmalonyl-CoA mutase and methionine synthase utilize transmethylation via B12 and when incapable of doing so, result in a buildup of MMA and homocysteine, respectively. Despite the lack of typical etiologies for B12 deficiency in our patient, the finding of a borderline low B12 level, with severely elevated levels of MMA and homocysteine, ultimately led to the diagnosis.Subacute combined degeneration secondary to NO use typically resolves with abstinence and supplementation of B12 over the course of months to years, as in this case. Untreated, or with continued NO use, functional B12 deficiency can lead to permanent neurologic, cardiac, hematologic, and immunologic dysfunction.
Conclusions: Inhaled nitrous oxide can result in functional B12 deficiency, even with normal levels of B12. In patients with known or suspected use of NO, investigation into possible B12 deficiency should be taken, including testing of MMA level. In patients with B12 deficiency without obvious cause, investigation into exposure to inhaled NO, whether on purpose or by accident, should be undertaken.
