Cause Of Cyanosis Research Articles

Interventional management of an unusual cause of cyanosis in repaired tetralogy of Fallot

ABSTRACT Arterial desaturation following surgical repair of tetralogy of Fallot (TOF) is rare. In most instances, it results from residual right ventricular outflow tract obstruction, causing right-to-left shunt across residual interatrial or interventricular communication. In this report, we present an unusual scenario of arterial desaturation due to a recanalized left cardinal vein in a child with repaired TOF. We also discuss stepwise evaluation that led to successful identification and occlusion of the abnormal venous channel by percutaneous device closure.

Nucleated Red Blood Cell Counts Differentiate Cardiac from Respiratory Causes of Cyanosis at Birth.

Tissue hypoxia increases erythropoietin production and release of immature erythrocytes that can be measured using nucleated red blood cell counts (nRBC). We hypothesized that hypoxia due to congenital heart disease (CHD) is chronic and is better tolerated than hypoxia due to respiratory disease (RD), which is an acute stress in newborns leading to higher nRBC. This study assesses the utility of nRBC as a marker to differentiate hypoxia due to CHD vs RD in term neonates. This was a single-center, retrospective study of term neonates with cyanosis from 2015 to 2022. Neonates < 37weeks of gestation, with hypoxic-ischemic encephalopathy, and those with other causes of cyanosis were excluded. The patients were divided into 2 groups: cyanotic CHD and cyanotic RD. Clinical and laboratory data done within 12h and 24-36h after birth were collected. Data are represented as median and Interquartile range. Of 189 patients with cyanosis, 80 had CHD and 109 had RD. The absolute nRBC count at ≤ 12h of age was lower in the CHD (360 cells/mm3) compared to RD group (2340 cells/mm3) despite the CHD group having significantly lower baseline saturations. A value of 1070 cells/mm3 was highly sensitive and specific for differentiating CHD from RD. The positive predictive value for this cut-off value of 1070 cells/mm3 was 0.94 and the negative predictive value was 0.89. The absolute nRBC is a simple screening test and is available worldwide. A nRBC < 1070 cells/mm3 in cyanotic newborns should hasten the search for CHD etiology with the possible need for prostaglandin therapy.

A Narrative Review on Management of Cyanosis in Neonates

A bluish coloring of the skin or mucous membrane that is characteristic of the medical condition cyanosis can be visible around the lips, fingers, and toes. It is one of the indications of respiratory distress in infants that can be brought on by inadequate circulation and low levels of oxygenated blood. There are two basic causes of cyanosis, cardiac and pulmonary. Medical professionals are constantly very concerned about accurately diagnosing and treating newborns with congenital heart disease (CHD), despite the fact that prenatal diagnostic methods have significantly improved. Although they are physiologically entirely different from one another, ductus dependent congenital cardiac abnormalities can be divided into the ductus dependent systemic or pulmonary sickness. When developing the treatment plan, the clinical state and cardiac abnormalities must be taken into consideration. Many life-threatening conditions may not show signs right away after delivery, and the majority of clinical and physical symptoms are ambiguous, which makes a diagnosis difficult. Careful evaluation is required, and when clinical data, electrocardiograms, and chest X-rays are used. The newborn must be identified as being at such high risk right once, and prompt medical attention is essential to reducing mortality and morbidity

Catheter interventional closure of veno-venous collaterals in cyanotic patients after partial cavopulmonary shunts in pediatric patients: clinical practice review.

The development of veno-venous collaterals is an important and treatable cause of cyanosis in patients who had undergone partial cavo-pulmonary connection (PCPC) operations. Nevertheless, the literature on this complicated therapeutic option is sparse. Patients can present cyanosis either immediately after the operation (<30 days), which delays or hinders discharge from the intensive care unit or cyanosis may occur late: (>30 days and/or in another hospital admission), after the operation. Hence, transcatheter closure of veno-venous collaterals is the treatment of choice. Four patients were selected who showed cyanosis at variable durations after PCPC; the morphology of the collaterals and their hemodynamic effect was described and the strategy for closure of such abnormal vessels is suggested. Veno-venous collaterals described in our series were seen originating mainly or mostly from innominate vein angles. The drainage sites were either above the diaphragm into a cardiac structure: the coronary sinus (CS) and/or atria; or below the diaphragm into the inferior vena cava (IVC) or hepatic veins through the paravertebral venous system and/or the azygous system. It is stated in the literature that several types of devices and coils can be used to close the collaterals such as the Amplatzer vascular plugs (AVPs), Amplatzer duct occluder II (ADOII), non-detachable and detachable coils. In this clinical review, the technical details that determine device type and size are explained. The recent generations of hydrogel-coated coils were also used in this series of patients to close the difficult types of collaterals with better results. All described vessels were closed successfully, without any complications. The patients had a significant rise in their transcutaneous oxygen saturations and hence, a clear clinical benefit.

Congenital methemoglobinemia and abnormal hemoglobin M variant in a newborn with cyanosis

Congenital methemoglobinemia, especially caused by pathological hemoglobin M, is an extremely rare cause of cyanosis in newborns. The time to onset and severity of clinical manifestations in hemoglobin M disease depends on which globin chain the mutation occurred in.Purpose. To present the case of congenital methemoglobinemia associated with hemoglobin M disease, not recognized in the neonatal period, to summarize the data on diagnosis, therapy, and prognosis for this pathology.Clinical case. In a full-term child without organ pathology, the development of diffuse cyanosis in the early neonatal period, a decrease in pSO2 of 70%, resistant to oxygen therapy, and increasing anemia were noted. The level of methemoglobin is up to a maximum of 17%. A decrease in the level of methemoglobin to 5.7% and stabilization of pSO2 &gt;90% were obtained after two transfusions of erythrocyte suspension. No pathological forms of hemoglobin were detected during electrophoresis on the 5th day of life. Repeated electrophoresis at the age of 5 months revealed a pathological hemoglobin fraction of 8.9% corresponding to hemoglobin M Iwate. During the first year of observation, the growth and development of the child corresponds to the age norm. Stable acrocyanosis. Methemoglobin in the blood remains at the level of 8.7–8.9% without specific therapy for the last 6 months.Conclusion. The diagnosis of congenital methemoglobinemia due to the presence of defective hemoglobin M (M-hemoglobinopathy) was established basing on the high persistent level of methemoglobin (9–12%) and hemoglobin electrophoresis identified an abnormal hemoglobin M (HbM Iwate) variant.

Case report of congenital methemoglobinemia: an uncommon cause of neonatal cyanosis

BackgroundMethemoglobinemia can be an acquired or congenital condition. The acquired form occurs from exposure to oxidative agents. Congenital methemoglobinemia is a rare and potentially life-threatening cause of cyanosis in newborns that can be caused by either cytochrome B5 reductase or hemoglobin variants known as Hemoglobin M.Case presentationA term male infant developed cyanosis and hypoxia shortly after birth after an uncomplicated pregnancy, with oxygen saturations persistently 70–80% despite 1.0 FiO2 and respiratory support of CPAP+ 6 cm H2O. Pre- and post-ductal saturations were equal and remained below 85%. Initial radiographic and echography imaging was normal. Capillary blood gas values were reassuring with normal pH and an elevated pO2. Investigations to rule out hemolysis and end-organ dysfunction were within acceptable range. Given the absence of clear cardiac or pulmonary etiology of persistent cyanosis, hematologic causes such as methemoglobinemia were explored. No family history was available at the time of transfer to our institution. Unconjugated hyperbilirubinemia > 5 mg/dL (442 μmol/L) interfered with laboratory equipment measurement, making accurate methemoglobin levels unattainable despite multiple attempts. Initial treatment with methylene blue or ascorbic acid was considered. However, upon arrival of the presumed biological father, a thorough history revealed an extensive paternal family history of neonatal cyanosis due to a rare mutation resulting in a hemoglobin M variant. Given this new information, hematology recommended supportive care as well as further testing to confirm the diagnosis of congenital methemoglobinopathy. Whole genome sequencing revealed a likely pathogenic variation in hemoglobin. The neonate was discharged home at 2 weeks of age on full oral feeds with 0.25 L/min nasal cannula as respiratory support, with close outpatient follow-up. By 5 weeks of age, he was weaned off respiratory support.ConclusionCongenital methemoglobinemia should be considered in the differential diagnosis for newborns with persistent hypoxemia despite normal imaging and laboratory values. Accurate quantification of methemoglobin concentrations is challenging in neonates due to the presence of other substances that absorb light at similar wavelengths, including HbF, bilirubin, and lipids.

A rare cause of cyanosis in neonatal age: Cor triatriatum dexter.

Cor triatriatum dexter is an extremely rare congenital anomaly that is caused by the partitioning of the right atrium by a broad sheet of tissue due to the persistence of the right sinus venosus valve. We describe a rare case of prominent right sinus venosus valve (cor triatriatum dexter) with consequent right-to-left shunt across the patent foramen ovale in a newborn with significant cyanosis.

Acquired methemoglobinemia in children presenting to Italian pediatric emergency departments: a multicenter report

Introduction Methemoglobinemia (MetHb) is a rare inherited or acquired cause of cyanosis in children. Owing to its rarity, case reports and case series are mostly available in the current literature. This study reports data on a large sample of children with acquired MetHb. Methods Data on patients admitted for acquired MetHb between January 2007 to December 2020 was extracted from the databases of five Italian pediatric emergency departments (EDs). Demographical and clinical characteristics was reported and discussed. Results Nineteen cases of acquired MetHb were evaluated. Ten patients (52.6%) were male and 9 (47.4%) were female. The median age was 8.23 months. The median time from trigger to symptom onset was 6 hours. Mostly, the intoxication presumptively occurred by home ingestion of contaminated food, mainly badly preserved vegetable broth. All patients were cyanotic at admission, most patients also presented tachycardia and/or tachypnea, and two patients were comatose. Antidotal therapy with methylene blue was given in 14 patients (73.7%). The median hospital stay was 2 days. All patients survived. Discussion As MetHb leads to the pathognomonic brown blood discoloration, blood gas analysis is mandatory immediately upon hospital arrival of a cyanotic patient. A correct medical history is crucial to identify the trigger and remove it. In our sample, the age onset was much lower than in the previous literature, and MetHb mainly due to ingestion of contaminated vegetable broth. Methylene blue led to a rapid recovery in all patients. Oxygen therapy may well lead to complete recovery when methemoglobin levels do not exceed 30% in asymptomatic and 20% in mildly symptomatic patients. Conclusions The diagnosis and management of acquired MetHb in the emergency setting requires acknowledgment of this condition as a cause of cyanosis in the weaning child. Indeed, when promptly recognized and treated, this severe condition rapidly resolves with no significant acute sequelae.

Total anomalous systemic venous connection with left isomerism in an adult - A rare cause of cyanosis

Total anomalous systemic venous connection with left isomerism in an adult - A rare cause of cyanosis

EYES DO NOT SEE WHAT MIND DOESN'T SEEK: A PUZZLING CASE OF METHEMOGLOBINEMIA

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Methemoglobinemia must be considered in the differential diagnosis of hypoxia not improving with supplemental oxygen. CASE PRESENTATION: An 84-year-old male patient with a past medical history of Atrial fibrillation, scleritis, hypertension presented with complaints of fever, chills, shortness of breath for 5 days. Medication history included triamterene/hydrochlorothiazide, Amiodarone, warfarin, ezetimibe, prednisone, and methotrexate. On presentation, the patient was saturating 79% on ambient air and was put on Hiflo nasal oxygen, and saturation improved to 95% on Fi02 100% at 35 l/min. The lab was significant for WBC count of 12.1, procalcitonin 1.06, a chest x-ray revealed bilateral opacities left greater than right with air bronchograms. Chest CT done showed bilateral ground-glass opacities with interposed consolidation. Bronchoscopy was deferred due to the clinical condition of the patient The patient was started on cefepime, doxycycline, methylprednisone, primaquine, and clindamycin for empiric treatment of PCP pneumonia with superimposed bacterial pneumonia and was transferred to ICU for hypotension secondary to sepsis. Pt initially improved clinically and Hiflo was weaned to Fi02 of 50% and maintained saturation above 95%. Over the course of 3-4 days after downgrading to the medical floor, the patient's oxygen requirement uptrend, though a repeat CT scan of the chest showed radiological improvement. An ABG with co-oximetry done showed Po2 of 302 mmHg, saturation of 91 % on Fi02 of 100%, and Methemoglobin content of 7.8%. IV methylene blue infusion was given and the patient's respiratory status improved with the Fio2 requirement coming down. Repeat ABG with co-oximetry showed a methemoglobin level of 2.4%. Repeat labs did not show evidence of hemolysis and G6PD levels were normal. The patient's increased susceptibility to methemoglobinemia would have been due to drug interaction as he is on thiazide diuretic and was started on primaquine increasing the oxidative stress coupled with oxidative stress secondary to sepsis. Primaquine was discontinued and started on atovaquone for PCP treatment. The patient continued to improve clinically. DISCUSSION: Methemoglobinemia can occur after exposure to a number of medications, including primaquine, sulfonamides, nitrates, topical anesthetics. Methemoglobin is the oxidized form of Hb, Oxygen does not bind as easily to the heme subunit with the ferric form of iron. The remaining heme sites have increased affinity for oxygen, resulting in decreased ability to release oxygen to tissues, causing left-shift of the oxygen-hemoglobin dissociation curve leading to tissue hypoxia. A clue to diagnosis is the cyanosis-saturation gap. CONCLUSIONS: An obvious mismatch between the PaO2 (which is >>100 mm) versus the pulse oximetry ( typically ~80-90%), known as the PaO2-saturation gap, is a clue to the diagnosis of methemoglobinemia REFERENCE #1: Gibson QH. The reduction of methemoglobin in red blood cells and studies on the cause of idiopathic methemoglobinemia. Biochem J 1948;42: 13-23. REFERENCE #2: Ohashi K, Yukioka H, Hayashi M, Asada A. Elevated methemoglobin in patients with sepsis. Acta Anaesthesiol Scand 1998;42: 713-716. REFERENCE #3: Beutler E. Methemoglobinemia and other causes of cyanosis. In: Beutler E, Lichtman MA, Coller BS, Kipps TJ, eds. Williams Hematology. 5th ed. New York: McGraw-Hill; 1994: 654-662. DISCLOSURES: No relevant relationships by Santhosh Bayambe, source=Web Response No relevant relationships by Nadish Garg, source=Web Response No relevant relationships by Killol Patel, source=Web Response No relevant relationships by ARCHANA SREEKANTAN NAIR, source=Web Response

A Boy with Nephrotic Syndrome and Methemoglobinemia: A Diagnostic Challenge

Methemoglobinemia is a rare disease characterized by the elevated levels of methemoglobin in the blood. It may be congenital or acquired. Co-trimoxazole is an antibiotic that belongs to the sulfone group. Sulfone group drugs may produce drug-induced acquired methemoglobinemia. Methemoglobin is an oxidized form of hemoglobin that has an increased affinity to oxygen and a reduced ability to release oxygen to tissues. High levels of methemoglobin inred blood cells cause tissue hypoxia. This disorder may present with several symptoms such as cyanosis, fatigue, dyspnea, and headache. Because it is a rare cause of cyanosis and hypoxemia, the diagnosis of methemoglobinemia is often delayed. We herein discuss a five-year-old boy with steroid-resistant nephrotic syndrome who presented with exertional dyspnea and cyanosis and was later diagnosed as a case of co-trimoxazole-induced methemoglobinemia.

A rare and curable cause of cyanosis – Congenital portosystemic shunts

Congenital portosystemic shunts (CPSSs) are rare developmental vascular anomalies which are classified into extrahepatic and intrahepatic malformations. Here, we report a 7-year-old girl who presented with a history of progressive dyspnea, pandigital cyanosis, and clubbing. On evaluation, she was found to have a rare combination of both type II extrahepatic and intrahepatic portosystemic shunts which were closed endovascularly in the same setting. Diagnosis of CPSS needs a very high index of clinical suspicion. Timely diagnosis with specific imaging modalities will help in deciding the treatment strategy and may prevent long-term complications.

Acquired methemoglobinemia presenting to the pediatric emergency department: a clinical challenge.

Acquired methemoglobinemia (MetHb) is an uncommon presentation of cyanosis in the pediatric emergency department (ED), making its diagnosis and management a clinical challenge. Through this case series we hope to improve clinician ability to recognize the potential for MetHb in pediatric ED patients and to avoid overlooking this important cause of cyanosis. This was a case series using a health records review, investigating patients diagnosed with MetHb at our pediatric ED during 2007-2018. We included only cases with methemoglobin saturation ≥5%. Ten patients were diagnosed with MetHb in our pediatric ED during the study period. Five had an underlying hematologic disease who received a pharmacologic trigger known to induce MetHb as well (four dapsone, one rasburicase). The other five patients were previously healthy, who presented with a clinical picture of hemolytic anemia, all of whom were diagnosed with previously unknown glucose-6-phosphate dehydrogenase (G6PD) deficiency. Two of the patients received methylene blue, and five patients needed packed red blood cells. All of the patients survived the acute MetHb episode. Acquired MetHb in the pediatric ED is a rare but important cause of cyanosis. Diagnosis and management of acute, acquired MetHb in the ED requires a high level of suspicion, and a background knowledge of the common precipitants and underlying conditions associated with this condition. We hope this case series will help ED physicians to consider MetHb in pediatric patients presenting with cyanosis and persistent hypoxia. Exposure to known precipitants (e.g., medications and foods), particularly in the setting of active treatment for malignancy or with symptoms of hemolytic anemia should further increase suspicion.

Methemoglobinemia in a Newborn

Methaemoglobinaemia in a new born is a rare cause of cyanosis. We report a case of a new born presented with cyanosis and with normal cardio-pulmonary system. He was diagnosed as methemoglobinemia due to persistent cyanosis despite administration of oxygen and arterial blood gas collection appeared chocolate brown in colour. As methaemoglobin report was in mild range (11.7%), he was treated symptomatically.

Anomalous communication between pulmonary artery and left atrium: A rare cause of cyanosis

Anomalous communication between pulmonary artery and left atrium: A rare cause of cyanosis

Methemoglobinemia due to local anesthesia: a rare cause of cyanosis and chest pain after placement of implantable cardioverter defibrillator.

Although methemoglobinemia is rare in adulthood, it may have fatal consequences if unnoticed. We planned to implant an implantable cardioverter defibrillator ICD in a 50-year-old male patient for primary prevention. Following sterile draping, prilocaine 5 mg/kg (400 mg) was injected subcutaneously for local anesthesia. We injected an additional dose of 200 mg due to pain during subclavian vein puncture. A DDD-R ICD was placed successfully within approximately 40 minutes. The patient complained of sudden chest pain and dyspnea 15 minutes after bed rest and was transferred to the coronary care unit due to cyanosis and deterioration of general status. Physical examination revealed blood pressure of 110/80 mmHg, pulse rate of 110 bpm, and otherwise unremarkable signs. Peripheral oxygen saturation was determined as 83% by pulse oximeter. Possible pneumothorax and cardiac perforation were excluded by emergency chest radiograph and echocardiography. Blood gas analyses was performed to assess for methemoglobinemia, which revealed pH 7.41, pCO2 40 mmHg, oxygen saturation 98.2%, and methemoglobin 7.9% that peaked to 12.3%. Methylene blue (1%) was slowly injected over 10 minutes at a dose of 1 mg/kg. Cyanosis waned and methemoglobin values decreased to 4.1%, 2.1%, and 1.1% at 2, 8, and 16 hours following the administration, respectively. The patient was safely discharged 2 days after implantation of pacemaker. Methemoglobinemia should be considered in cases presenting with cyanosis, non-diagnostic ECG, and a discrepancy in oxygen saturation between pulse oximetry and blood gas analyses.

Transcatheter pulmonary valvuloplasty with coronary balloon for critical pulmonary atresia with intact ventricular septum in a neonate

Pulmonary atresia with intact ventricular septum is a rare cause of cyanosis in a newborn. The prognosis and treatment of the condition depend on the pulmonary anatomy as well as the state of the right ventricle. We present a case where the patient presented with acute desaturation, and we had to do an emergency pulmonary valvotomy, using coronary wires and balloons, as a lifesaving procedure. The saturation improved on the table, and the patient could be discharged from hospital in a stable state. This particular case shows that opening an atretic pulmonary valve is a viable option and coronary wires and balloons can be used for the purpose.

Case of methemoglobinemia in an infant with cyanosis

Methemoglobinemia refers to a group of hemoglobinopathies which characterized by an increase of the hemoglobin (Hb) amount, in which oxidation of ferrous iron to ferric iron is observed with the loss of the ability to reversibly bond with oxygen and the development of hemic hypoxia. Cyanosis is the most common symptom of methemoglobinemia and is the reason for the differential diagnosis of cardiovascular and respiratory diseases. Timely determination of the cause of cyanosis in a newborn can be a difficult task. By origin, cyanosis in children at birth and in the first weeks of life is cardiac, respiratory, cerebral, metabolic, and hematological. The prognostic value of cyanosis is different for different diseases. Pronounced and persistent cyanosis in diseases of the lungs and heart indicates a high degree of respiratory or heart failure and prognostic unfavorable. Most of the causes of acute cyanosis is an immediate threat to the life of the patient. Prolonged tissue hypoxia in patients with persistent cyanosis leads to the development of secondary erythrocytosis, an hematocrit increase, blood viscosity, which worsens the microcirculation in tissues, aggravating the deficit of tissue respiration. If cyanosis is detected in infants, differential diagnosis should include hemoglobinopathies, in particular, methemoglobinemia. A carefully collected medical history, the exclusion of all possible causes of cyanosis and hypoxemia, and the assessment of methemoglobin in the blood allow a timely diagnosis. The purpose of the article is to describe the clinical observation of methemoglobinemia in an infant with a detailed discussion of the characteristics of the case.

A case of DAPSONE INDUCED METHEMOGLOBINEMIA

Methemoglobinemia (MetHb) being a rare cause of cyanosis is generally not considered in its differential diagnosis. Methemoglobinemia is an abnormal Hb produced physiologically by auto-oxidation. If this process of auto oxidation is impaired either due to genetic defect or due to exogenous drugs/ toxins, its level starts rising. Once it is > 3%, tissue hypoxia ensues. Here is a case of dapsone induced MetHb and is reported in a young girl with central cyanosis, and was treated successfully with methylene blue. Methemoglobinemia should be considered in differential diagnoses of cyanosed patient with normal ABGs, PaO2 and cardio-respiratory status. If left untreated, the disease can be fatal.

PS1201 : MOLECULAR STUDY OF RED CELL NADH‐CYTOCHROME B5 REDUCTASE DEFICIENCY IN 21 INDIAN PATIENTS WITH RECESSIVE HEREDITARY METHEMOGLOBINAEMIA

Background:Recessive congenital methemoglobinemia (RCM) due to NADH–cytochrome b5 reductase 3 (cyb5r3) deficiencies is an autosomal recessive disorder that occurs sporadically worldwide. Over seventy six different mutations have been described for RCM.Aims:The aim of this study molecular basis of RCM in 21 patients and prenatal diagnosis in 4 cases with severe mental retardation and neurological disabilities along with a comprehensive review of all the pathogenic mutations in cyb5r3 and their molecular pathology in RCM.Methods:Twenty‐five cases were analyzed amongst which 21 cases were diagnosed with NADH‐CYB5R deficiency based on significantly reduced NADH‐CYB5R activity while 4 were referred for prenatal screening. The study has been approved by the National Institute of Immunohematology Ethical committee and as per protocol, written informed consents were obtained from all the patients or their parents. Complete blood counts were measured by automated hematology analyzer XN (Sysmex, Kobe, Japan). Methemoglobin estimation, G6PD, and NADH‐Cyb5R enzyme assay were performed as described by Beutler et al. method. DNA was extracted from the Blood/CVS using Qiagen DNA extraction kit according to the manufacturer's instructions. PCR exon‐specific primers were utilized and PCR and Sanger's sequencing was performed by a standard method. Molecular modeling of cyb5r3 was done using the PYMOL and SWISS‐PDB viewer tool.Results:In the 21 patients analyzed in this study, all index cases from twenty unrelated families were referred for the cause of cyanosis. All patients showed mild to moderate cyanosis and few patients had mental retardation or any neurologic abnormalities. Methemoglobin levels were increased, varying from 8.5% to 65%. NADH‐Cyb5r3 activity was seen to be in the range of 6 to 19%. In the molecular analysis, eighteen mutations (fourteen missense, one deletion, one‐stop codon, and 1 splice‐site mutation) were observed (Figure 1) in this study. Amongst fourteen missense mutations 5 were novel mutations [c.105A&gt;C (p.Thr35Arg), c.192C&gt;G (p.Leu64Val), c.312G&gt;T (p.Gly104Cys), c.354C&gt;T (p.His118Tyr) and c.470T&gt;G (p.Phe157Cys)]. Over seventy‐six different mutations have been described for RCM globally (Figure 1). Same mutations are associated with the severe form with a neurological disorder (RCM type 2) were associated with the FAD‐binding domain of the protein while rests were located in the other domains of the protein (RCM Type 1). One of the prenatal analyses showed splice‐site mutation p.Gly76Ser at nucleotides 226 in exon 3 of the CYB5R3 gene in the homozygous state while in another one it was found in the heterozygous state. In the third case stop codon mutation p.Gln77X at nucleotide position 229 in exon 4 was seen in the heterozygous condition. In the fourth case, normal wild type genotype for the CYB5R3 gene was found.Summary/Conclusion:This study presents the results of the first molecular study of a large number of cases of NADH cytochrome b5 reductase deficiency in India Molecular modeling of all the mutations reported in CYB5R3 justifies the association of the mutations with the varying severity of the disease. Knowing the profile of mutations in families with severe neurological disorders allowed us to offer a prenatal diagnosis of RCM Type 2 for the first time in the Indian population. Thus severity and recurrence risk of type II RCM merit could be prevented by prenatal diagnosis in affected families.image