ACATALASEMIA  is an autosomal recessive constitutional disorder caused by the absence of catalase activity. It was discovered by Takahara1in 1946. Catalase  is an enzyme that catalyzes the conversion of hydrogen peroxide to water and oxygen. In acatalasemia, the catalase is absent in the mucosa, skin, muscle, sternal marrow, appendix, and liver tissue.2We describe our experience with a case of acatalasemia associated with methemoglobinemia that was caused by hydrogen peroxide solution during anesthesia.

The patient was a 71-yr-old man who had been given a diagnosis of laryngeal cancer and was scheduled to undergo complete laryngectomy with neck dissection. His family history was not relevant to the current disorder.

General anesthesia was induced with thiamylal and vecuronium and maintained with 50% oxygen, 50% nitrous oxide, and 1–2% isoflurane. During induction of anesthesia, the percutaneous oxygen saturation (Spo2) was 100%, and hemodynamic variables were stable. The oral cavity and larynx were disinfected with 300 ml of a 1:2 dilution of 3% hydrogen peroxide; the neck was disinfected with 7% povidone iodine. Approximately 10 min after starting the operation (approximately 20 min after disinfection), the Spo2rapidly decreased to 80%, and the blood in the surgical field turned blackish brown. Arterial blood gas measurement and hemoglobin analysis revealed dissociation between the partial pressure of arterial oxygen (Pao2, 235 mmHg) and the arterial oxygen saturation (Sao2, 87.5%, actually measured value). The methemoglobin concentration was 11%, and methemoglobinemia was diagnosed, although its cause was unclear. The patient was intravenously given 2,000 mg ascorbic acid, and surgery was resumed. While the patient was breathing 100% oxygen, the Sao2increased to 89.7% and the Pao2increased to 435 mmHg; the methemoglobin concentration decreased to 7.5%.

However, on removing the surgical drape from the face, an extensive area of edema, vacuoles, and erosions was found on the cheeks, lips, oral cavity, and pharyngeal mucosa. Awakening was normal. The methemoglobin concentration on postoperative day 3 was normal (0.5%).

When hydrogen peroxide was applied to a sample of the patient’s blood, bubbling was weaker than that with the blood of a healthy subject, and the blood sample turned dark brown. When the patient’s forearm was scratched and hydrogen peroxide was applied, vacuoles developed after 15 min. These results led to a differential diagnosis of (1) absence of reduced nicotinamide adenine dinucleotide methemoglobin-converting enzyme; (2) absence of glyceraldehyde-3-phosphate dehydrogenase, glucose-6-phosphate dehydrogenase, or pyruvate oxidase; (3) absence of glutathione reductase or glutathione peroxidase; or (4) abnormal catalase activity.3Erythrocyte catalase activity measured by the method described by Beutler4was markedly decreased (28 U/g hemoglobin; normal range, 129,000–177,000 units/g hemoglobin). The diagnosis was acatalasemia.

Because acatalasemia is an autosomal recessive disorder, pedigree analysis was performed with the cooperation of the patient’s family. The patient’s parents were half cousins. His mother had hypocatalasemia with approximately half of the catalase activity of a normal person. The patient’s father had already died but was assumed to have had acatalasemia or hypocatalasemia. The patient’s spouse was normal, but all three of their children had hypocatalasemia. The underlying genetic abnormality was found to be Japanese type on gene analysis.5There are approximately 50 known unrelated Japanese-type acatalasemia families, characterized by the near total loss of catalase activity because of a splicing mutation.

Catalase serves to protect the cells from the toxic effects of hydrogen peroxide by catalyzing its decomposition into molecular oxygen and water.6In acatalasemia patients, hydrogen peroxide does not decompose, and it acts as an oxidant of hemoglobin, resulting in methemoglobinemia. In healthy patients, hydrogen peroxide causes the formation of oxygen bubbles, without any change in blood color. An important feature of our case was that a blood sample turned blackish brown or chocolate colored on the addition of hydrogen peroxide, without the formation of oxygen bubbles. Approximately half of all patients with acatalasemia have progressive gangrenous stomatitis during childhood, whereas the other half are asymptomatic, as in the current case. Progressive gangrenous stomatitis develops because of inability to process hydrogen peroxide produced by oral flora. In the current case, the hydrogen peroxide used to wash the oral cavity disturbed mucosal cells and penetrated to the capillaries, where it converted hemoglobin to methemoglobin. The increase in methemoglobin resulted in localized oxygen deficiency, causing the formation of edema and ulcers in the oral cavity and pharynx.1Methemoglobinemia is diagnosed when the methemoglobin concentration increases to the equivalent of at least 1% of the total hemoglobin concentration such as in acatalasemia patients. Our case was classified as acquired methemoglobinemia. Early diagnosis was facilitated by discoloration of blood, measurement of percutaneous oxygen saturation, and analysis of hemoglobin.7Methylene blue is the first-line antidote for methemoglobinemia, provided there is no glucose-6-phosphate dehydrogenase deficiency. We used ascorbic acid as an antioxidant of methemoglobin because the cause was unclear during surgery.

The possibility of acatalasemia should be borne in mind by physicians who use oxidizing agents such as hydrogen peroxide at the time of anesthesia.

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