Congenital Methemoglobinemia BushraTar iq and Sheila Karan

Princess Durru Shehwar Children's Hospital, Purani Have& Hyderabad

Abstract. A case of congenital methemoglobinemia presenting at birth is reported. The clinical signs, differential diagnosis, pathogenesis and management of this disorder are discussed. (Indian J ?ediatr 2000; 67 (2): 159-160)

Key words : Methemoglobinemia; Pathogenesis

Methemoglobinemia is a relatively rare disorder which may be caused by either a genetic disorder or may be acquired

secondary to toxins, drugs or certain noxious agents*'h Reported here is a case of a new born baby who presented

with this disorder on the first clay of life probably due to

NADH cytochrome B5 reductase enzyme system deficiency-. Recently a case of methemoglobinemia in a neonate

caused by maternal dapsone therapy was reported from Mumbai 3.

CASE REPORT

A 5 day old male baby was referred to Princess Durru

Shehwar Children's Hospital, Hyderabad in February, 1998

for bluish discoloration of lips, face and extremities since birth. The baby was born to a primigravida out of second degree consanguinous marriage at a private hospital at Karimnagar. There was no history of drug intake or exposure to nitritis or other oxidants in mother or baby. The infant was

delivered after full term normal vaginal delivery with history of cord around the neck and according to the parents, the

baby cried 8-10 minutes after birth. The Apgar score and details of resuscitation were not mentioned in the referral note. The baby was limp and blue at birth and hence was

referred to a paediatrician for further treatment. On examination, the baby was 2 kgs in weight and was term by gestational age assessment. There were no neurological signs and the baby was feeding well from the breast. However, it was noticed that the baby was becoming blue, on and off, for which the baby was referred to our hospital with a tentative diagnosis of cyanotic congenital heart disease.

On admission the baby was found to he stable, afebrile with no cardiac, respiratory or neurological signs. However, bluish grey discoloration of hands, feet, lips and face were

Reprint requests : Sheila Karan, Princess Durru Shehwar Children's Hospital, Purani, Haveli, Hyderabad - 500 002. Fax : 040-4577009

seen in room air but when oxygen was administered to the

baby the discoloration immediately changed to a pink hue particularly noticeable on soles, palms and lips. The baby was

kept under an oxygen hood with continuous oxygen therapy until such time that the diagnosis was established. Otherwise,

the baby was asymptomatic and was feeding well. The heart rate was 124/rain with no murmurs and

normal heart sounds. The respiratory rate was 45/rain with

no signs of respiratory distress. The anterior fontanelle, the pupils, tone of the limbs and neonatal reflexes were all normal. The cry and activity were good and all other systems

were essentially normal. The pO~ saturation was monitored continuously and was found to be normal at all times. The

blood gas values were also within normal limits. The cardiologist's opinion was sought to rule our

congenital heart disease. 2D ECHO and chest radiograph showed no abnormality thus ruling out a structural cardiac

lesion. The neurosonogram was also normal. In view of the above findings a tentative diagnosis of methemoglobinemia was entertained. Blood was sent for methemoglobin

estimation alongwith other haematological investigations which were as follows.

Haemoglobin-16.6 gm%, WBC count-6,700/cumm, N-

64%, L-31%, E-2%, M-3%, CRP raised to 12 mg/dl, S. calcium-7.40 mg/dl, RBS-4 mg/dl, G6PD screening test-

negative. The methemoglobin level in blood was 4 mg/dl (normal

1 mg/dl) which is equivalent to 25% of total Hb. The blood electrophoresis was found to be negative for Hb M. The

enzyme cytochrome B5 reductase estimation could not be done as bio-chemical facilities for this estimation were not

available. The baby was treated with incubator care, antibiotics and

intermittent 0 2 therapy initially. Once the diagnosis of methemoglobinemia was made, oral methylene blue

preparation was tried as the intravenous preparation was not

Indian Journal of Pediatrics, 2000; 67 (2) : 159-160

B. Tariq and S. Karan

available. Since the baby did not tolerate the oral methylene blue preparation, it was decided to try ascorbic acid. It was given in a dose of 300 mg/kg intravenously for the first two days. The cyanosis immediately disappeared and the baby did not require further O2 therapy. The methemoglobin levels fell to less than 1%.

After 2 days, oral Vit. C was given as 1 ml. tid for 5 days and on discharge, ascorbic acid, 10 drops bid was prescribed with a request to return if the symptoms recurred.

The baby was followed up every week for 3 weeks and was found asymptomatic. Instructions were given to continue oral ascorbic acid and return if the symptoms recurred.

DISCUSSION

The iron in haemoglobin is normally in the ferrous (Fe+2) state for O2 transport. Oxidation to the ferric (Fe+3) state yields methemoglobin which is non functional. The blood of healthy persons contains methemoglobin which is maintained at less than 1-2% by the cytochrome B5 reductase system. However, the neonate is unusually susceptible to the development of methemoglobinaemia on exposure to toxic agents on account of a physiological deficiency of the activity of the B5 reductase system in the newborn. Cyanosis is detectable when methemoglobin exceeds 10%, but symptoms develop only when the level exceed 30%.

is caused by the following Methmeglobinemia mechanisms '.4 :-

( A ) Heredilaw CongenHal

(i) Mainly deficiency of NADH cytochrome B5 reductase and 4 variants have been identified. The common one is type I where the defect is limited to erythrocytes and cyanosis is the only manifestation. Type II may be generalized and severe 4.

(ii) An abnormal haemoglobin M resistant to enzymatic reduction by methylene blue and detected by electrophoresis.

(B) Acquired

The other common type is the acquired variety where

there is oxidation of Fe+2 Hb to Fe+3 by drugs or environmental chemicals like nitrites, aniline dyes, dapsone, anti-malarials, anaesthetic agents ,.z3.4. Some of these agents

also exacerbate G6PD deficiency and the precipitation of unstable haemoglobin. Toxic or acquired methemoglobin may assume life threatening proportions especially at levels exceeding 50%. The specific antidote is methylene blue (1-2 mg/kg I.V.) but in milder cases, ascorbic acid is quite effective as seen in our case 4. One of the distinguishing

features between hereditary methemoglobin M disease and the enzymatic cytochromic B5 reductase deficiency and the acquired toxic variety is that the latter two are amenable to therapy with methylene blue, while the former is not. The met Hb M variety is caused by autosomal dominant transmission and can be diagnosed by electrophoresis. The diagnosis of NADH methemoglobin reductase deficiency which is transmitted as autosomal recessive can be confirmed by measuring the enzyme

activity in the RBC. This test is not readily available and could not be done in our case.

However, in view of the cyanosis at birth, absence of

exposure to drugs or noxious agents in the mother, neonate or in the environment, the absence of Hb M band on electrophoresis and the prompt response to treatment by ascorbic acid makes us presume that our case belongs to the group of congenital NADH reductase deficiency probably of the type I. However, one interesting feature was the history of severe asphyxia at birth and the cyanosis disappearing after administration of O2 to the baby. There have been reports of acidosis and infection precipitating methemoglobinemia in the new bornL

In our case hypoxia at birth could have been the trigger- ing agent in the production ofmethemoglobinemia.

REFERENCES

1. BUNN HF. Human haemoglob in - Normal and abnormal. In : Nathani DG(ed) Haematology of Infancy and Childhood, 4th edn. OSKIFA Philadelphia, WB Saunders Co. 1993; 698-731.

2. Ghai OP. Essentials of Pediatr/cs, 4th edn. Interprint 1996; 75-76.

3. Kabra N$, Nanavathi RN and Srinivasan G. Neonatal methemoglobinemia due to transplacental transfer of dapsone. Indian Pediatr. 1998; 35: 553-555.

4. Disorders of haemoglobin : Nelson Text Book of Pediat- r/cs. 15th edn. W.B. Saunders Co. 1996; 1401 - 1411.

5. Sagar S, Frayson GH, Fieg SA. Methaemoglob inemia associated with acidosis of probable renal origin. J Pediatr 1995; 126: 59-61.

160 Indian Journal of Pediatrics, 2000; 67 (2)