Severe phenotype of an Iranian patient with methemoglobinemia type II due to a novel mutation in the CYB5R3 gene

Methemoglobinemia is a rare autosomal recessive genetic disease caused by disruptive mutations in the CYB5R3 gene (MIM: 250800). Herein, a novel mutation is reported in an Iranian patient affected with methemoglobinemia type II. In this case study, the patient is precisely described according to the thoroughly carried-out examinations and workups. In so doing, the peripheral blood sample was collected to evaluate the methemoglobin level and NADH-CYB5R3 activity test. Moreover, whole-exome sequencing (WES) was recruited to identify the mutation leading to this disorder. Subsequently, Sanger sequencing was employed to confirm the detected mutation. Magnetic Resonance Imaging was also performed to explore the structure of the brain. As identified by the blood test, the methemoglobin level increased up to 25%, and the NADH-CYB5R3 enzyme activity showed to be 13.8 IU/g of Hb. A novel homozygous mutation in CYB5R3 (NM_001171661: g.23435C>T, c.181C>T, p.R61X, rs1210302322) was identified as the cause of the Methemoglobinemia type II in the proband. This nonsense mutation alters arginine to the stop codon at position 61 of protein in the FAD-binding domain that results in a truncated protein. The MRI revealed brain atrophy and corpus calusom hypoplasticity. It was established that this variation can lead to Methemoglobinemia. The proband demonstrates Methemoglobinemia type II phenotype such as cyanosis, severe mental retardation, microcephaly, as well as developmental delay. The brain MRI revealed brain atrophy and corpus calusom hypoplasticity. The cyanosis symptom is managed by daily ascorbic acid uptake.

A rare cause of cyanosis: Congenital methemoglobinemia

A 13-month-old infant, born from a consanguineous marriage. She presented isolated cyanosis. Physical examination was normal. Pulsed oxygen saturation was 94% in room air. Methemoglobin level was 39.4%. The diagnosis of congenital methemoglobinemia type I was retained. She was successfully treated with methylene blue infusions and ascobic acid.

Methemoglobinemia – Two Uncommon Presentations

Two rather different cases of methemoglobinemia are presented. The first case is an infant who had a circumcision procedure with prilocaine. The second case involves a 14-year-old girl who attempted suicide with an overdose of metoclopramide and butamirate citrate. The attention is drawn to differences in hospital admission and management especially with respect to methemoglobin level and age. If methemoglobin levels reach ≥ 10%, cyanosis would appear first. Symptoms of hypoxemia and diminished oxygen transport do not develop until levels reach 30 to 40%. Not only early intervention is crucial but also patients should not be discharged from the hospital too soon. Doctors should be able to identify high risk patients, paying a special attention to infants younger than three months old who might be at an increased risk of methemoglobinemia which is a potentially lethal complication of prilocaine. As for our second case, methemoglobin level has not increased, despite an overdose of metoclopramide. This may be due to age or timely elimination of toxic agents by gastric lavage, catharsis and administration of procyclidine.

The Pharmacotherapy of Blood Intoxication (Methmoglobinemia) Induce by Exposure to Ortho-Chlorobenzylidenemalononitrile (CS) in Public Protests

Background: Acquired Methemoglobinemia(MetHb) is a rare, but potentially serious and unfamiliarity with this complication may delay diagnosis and appropriate therapy. Presentation: A case of methemoglobinemia occurring in male teenage demonstrator as a complication of re-current exposure to ortho-chlorobenzylidenemalononitrile (CS) in public protests , the patient became cyanotic with a decrease in his level of consciousness, by the effect of hydrogen cyanide as by-product of (CS), resulting in a toxic methemoglobinemia level in his blood. Methemoglobin is incapable of carrying oxygen and is formed when the ferrous iron in the heme molecule is oxidized to the ferric state. The diagnosis should be entertained when cyanosis, unresponsive to 100% oxygen therapy, appears suddenly, especially when exposure to an oxidant agent is established. Treatment: The patient received a 1 mg/kg dose of methylene blue intravenously. A cooximetry done 1 hour later showed a methemoglobin level of 43%. A second 1 mg/kg dose of methylene blue was given and another hour later the methemoglobin level had dropped to 13%. The patient also showed clinical improvement with resolution of the cyanosis and return of his mental status to baseline. Conclusion: Methylene blue is the specific antidote, but should be reserved for more severe cases or if co-morbid conditions make mild hypoxia un advisable.

The Dose Makes the Poison: A Case Report of Acquired Methemoglobinemia

Background: Methemoglobinemia (MET) should be suspected in cases where cyanosis is not associated with signs and symptoms of lung and/or heart disease, or in a cyanotic child exhibiting discrepancies in the partial pressure of oxygen in the arterial blood, the blood oxygen saturation, and the clinical assessment. Case presentation: A 10-month-old girl was taken to the Pediatric Emergency Department for the acute, sudden development of significant peroral cyanosis associated with gray pigmentation of the skin. The problem was evidenced approximately one hour after she ingested a homemade puree of mixed vegetables, mainly composed of potatoes and chards that had been prepared three days before and had been kept in the refrigerator since then. Physical examination revealed that the child was very pale, conscious, and without respiratory distress. Oxygen saturation of hemoglobin in the arterial blood (SpO2) was 94%. Respiratory, cardiovascular, and abdominal evaluations did not reveal any signs of disease. A venous blood sample showed chocolate-colored blood with a pH of 7.404, a partial pressure of CO2 (pCO2) of 40.6 mmHg, a partial pressure of oxygen (pO2) of 21.3 mmHg, a bicarbonate level of 24 mmol/L, and an oxygen saturation (SO2%) of 47.7%. CO-oximetry carried out simultaneously identified a methemoglobin level of 22%. MET was suspected, and oxygen via nasal cannula at a rate of 4 L/min was given with only a slight increase in oxygen saturation (96%). Slow intravenous injection of methylene blue 1 mg/kg over a period of 5 min was initiated. The peripheral oxygen saturation (SpO2) gradually improved to 100% over the next 20 min. Forty minutes later, venous blood gas analysis showed a methemoglobin level of 0.9% with a complete resolution of cyanosis; supplemental oxygen via nasal cannula was therefore discontinued. During the next 36 h, the patient remained hemodynamically stable with good oxygenation on room air. Conclusions: This case report shows that recognition of acquired MET in a child with sudden cyanosis onset requires a high index of suspicion. In daily activities, there is a need to pay particular attention when homemade vegetable soups for child alimentation are prepared. The consumption of vegetable soups must occur immediately after preparation. Storage in a refrigerator must last no more than 24 h and if longer storage is needed, vegetable soups should be frozen.

SEVERE METHEMOGLOBINEMIA WITH UNKNOWN CAUSE – CASE REPORT

The aim: Methemoglobina is an oxidized form of hemoglobin, which normally doesn`t exceed 1%. It is stated that the amount of methemoglobin over 70% is fatal. The etiology vary, it might for instance be idiopathic, congenital or caused by toxic compounds. Material and methods: We analyzed the case of patient who had exceeded the fatal level of methemoglobin in a blood. Case report: Medical Air Rescue Team was dispatched to an 80-year-old patient who suddenly lost consciousness at home. Methemoglobin level was measured using Cobas b221 system and amounted to 75%. Given the patient’s advanced age, congenital causes of methemoglobinemia, such as deficiency of cytochrome-b5 reductase or nicotinamide adenine dinucleotide reductase (NADPH-MHb reductase) were excluded a priori. It seems that the only reason for the observed methemoglobinemia in the case of the examined patient was the acquired methemoglobinemia. The patient was treated with methylene blue with good results, her state improved soon. Despite a detailed interview, it was impossible to establish the etiological factor of methemoglobinemia. None of the household members exhibited clinical symptoms of poisoning with methemoglobinogenic substance. Although the methemoglobin level was potentially deadly, the patients survived. Conclusion: It should be stressed that it is not always possible to determine the etiological factor of the discussed disorders. Knowledge of the clinical picture of poisoning, as well as of the changes characteristic for poisoning and observable in laboratory, is extremely important, especially when it is not possible to determine the etiological factor of poisoning.

A Rare Case of Congenital Methemoglobinemia with secondary polycythemia- Case Report and Literature Review

Congenital heart diseases are common cause of congenital cyanosis with polycythaemia. Congenital methemoglobinemia is a rare cause of lifelong cyanosis with polycythemia. Congenital methemoglobinemia is caused either by enzyme deficiency or by an abnormal Hb (Hb M). Asymptomatic despite presence of severe cyanosis indicates this rare disorder. We are reporting a rare case of polycythemia with cyanosis due to congenital methemoglobinemia. The patient was referred to our centre and attended Hematology OPD (out-patient department) when his routine CBC revealed erythrocytosis. At that time, we found him severely cyanosed especially apparent on lips, tongue, hands and feet. He was diagnosed as a case of congenital methemoglobinemia with 38% blood methemoglobin level (normal value-0.00-2.00%). On view of life long persistent cyanosis, without any cardiopulmonary and neurological abnormality, consanguinity of parent’s marriage, dark colored blood with high methemoglobin level, a final diagnosis of Type I enzyme deficiency congenital methemoglobinemia was made. He was treated with oral ascorbic acid 250 mg twice daily. At follow up after 6 months his skin color improved and RBC count returned to normal. We are reporting this case of congenital methemoglobinemia for the first time in Bangladesh to emphasize the importance of this rare entity in the differential diagnosis of asymptomatic cyanosis with polycythemia.