Search

A Parents Group saving the lives of infants born with Rare Metabolic Disease: Part 1

The story of Vikas and Poonam Bhatia.


Vikas and Poonam Bhatia.


Metabolic acidosis, arterial blood gas, pyruvate dehydrogenase…. words that infiltrated the lexicon of 28-year-old Vikas Bhatia - uninvited, unwanted and, now, dreaded. The carefree Commerce graduate, Vikas had joined his father’s handloom business in Jaipur and was rearing to take it to new heights. Five years earlier he had been married to Poonam, and now they were going to welcome their first baby. The fairy tale life of Vikas seemed headed in the direction of ‘happily ever after’, and his poetic heart was ablaze.

Chahak Bhatia; Nov 21- 25, 1998

The Bhatia family was overjoyed as news came that Poonam had delivered her first baby, a boy, in a nursing home in Jaipur. The joy turned to mourning in just four days as the baby never made it home. Something was amiss right from Day 1. On Day 2 the baby took his first feed. Soon after, his body temperature dropped and he turned lethargic. He battled life for another 2 days and was gone.


A tide of rational and irrational questions vied for space in Vikas’s head as he tried to make sense of it all. How did this happen? Why such cruelty on a mere infant? Why my baby? Doctors had no definitive answers. The likely medical diagnosis- neonatal septicemia, a blood infection that could be caused during delivery, was no balm to Vikas. Family elders consoled him that infant mortality was more common than he imagined. He should overcome his grief and try again.

Lakshya Bhatia; Jan 16- 31, 2000

The Bhatia family prayed silently as Poonam delivered her second baby, again a boy, in a nursing home in Jaipur. The baby took his first feed on day 1, but history seemed to be repeating itself as he began to show the same adverse reactions. However, the paediatrician this time was more alert. He found the blood pH to be low (metabolic acidosis), and suspected that it could be a metabolic disorder due to a genetic defect that caused acidic conditions in the blood. The baby was obviously sick and in pain. The paediatrician advised the family to take the baby to New Delhi for more specialist care and diagnosis. In Delhi, the Doctors immediately sent the baby’s urine sample to Japan and blood sample to USA for analysis. Meanwhile the baby was kept under intensive care and the parents were not allowed in. Finally, when the Doctors realized they were fighting a losing battle they allowed Vikas to see the baby. The sight of his baby bleeding from the nose, with his lips turned blue, however gut wrenching, sowed the first seeds of a steely resolve in Vikas. He knew the end was near and, indeed the very next day the baby was no more. Having entered this world for a mere fifteen days, Lakshya left without ever knowing the warmth of his father’s bosom.

Vikas on a Buddhaesque quest for Truth

History had repeated itself on many counts. Vikas’s father had the same advice (for good reason, as we shall see later).. such things happen.. you are young.. just try again. The medical diagnosis was not as off-the-mark as neonatal septicemia, but it remained inconclusive. The reports that came from abroad were consistent with a number of metabolic disorders- primary lactic acidosis, urea cycle disorder, respiratory chain disorder, pyruvate decarboxylase deficiency– all clubbed under ‘inborn errors of metabolism’ (IEMs). Notably, where history did not repeat itself was Vikas’s reaction this time around. Rising above the profound grief (that envelops him to this day), he set out on a quest. Like Gautam Buddha who realized that Truth cannot be sought from the comfort of the royal palace, Vikas too discarded his middle-class security blanket and prepared himself to get to the root of it all. Unlike Gautam Buddha, however, Vikas had Poonam on his side, fully supporting him in this junoon. With remarkable clear-headedness he made some key observations-

  1. He needed a clear diagnosis of his sons’ ailment if tragedy was to be averted in future.

  2. Knowledge about IEMs was scant in the medical fraternity, but it was not non-existent and he must find it.

  3. He must understand the medical jargon enough to ask the right questions to the Doctors.

Vikas started working towards his Everestian goal by first meticulously preparing the case files of his two babies. He became tech savvy to gather medical information from the internet and chew on it. Next he literally scoured the length and breadth of the country trying to meet Doctors who could enlighten him about the possible diagnosis, and tell him what steps he could take to have a healthy baby in future. Getting appointments with top Doctors was not a mean job, but Vikas was not giving up.


"In Cochin I once waited for 8 hours to consult the doctor. In yet another case I left the case files of my babies outside the doctor’s residence when he was not available at home in Ahmedabad. I remained on my toes for 5 consecutive years,” recalls Vikas.

Enlightenment regarding inborn errors of metabolism (IEMs)

So what did Vikas learn? Our body is a sophisticated chemical factory, furiously at work 24X7. The sum total of all chemical reactions taking place in the body is called metabolism. They are all driven by catalysts called enzymes. Some of these reactions break down food molecules to release energy needed for body functions. Other reactions construct larger molecules from simpler building blocks needed for growth and maintenance. The amazing fact is that billions of these reactions take place all the time in an interactive mode, with the product of one reaction being used as the starting point of another. The whole system is so well orchestrated that we hardly notice anything going amiss, except in a drastic perturbation like a genetic defect in an enzyme. IEMs are caused due to such genetic defects.

The diagnostic conundrum of Lakshya - the likely suspects

Why was it so difficult for Doctors to arrive at a definitive diagnosis for Lakshya? Mainly because metabolic pathways work in networks where the primary defect is sometimes concealed by too many secondary outcomes. There are just too many alibis- enough to confound even a Sherlock Holmes to nail down the actual offender. To understand the intricacies of this diagnostic journey we need to peep into the case file of Lakshya, and get at least a superficial glimpse.

Lakshya had presented with metabolic acidosis, a condition in which there is too much acid in the body fluids. There can be many reasons for metabolic acidosis. One of them is due to overproduction of lactic acid, which was the case with Lakshya. Acidosis was persisting in spite of bicarbonate drip and peritoneal dialysis, and lactate remained high. This led to the suspicion of IEM. His blood sample was sent to USA for testing in the Supplemental newborn screening program which tests for a number of metabolites. This analysis showed elevation of an amino acid called citrulline which is indicative of defects in the urea cycle, leading to diseases like citrullinemia or argininosuccinic aciduria. The urea cycle is a cycle of reactions that prevents toxic build-up of ammonia in the blood by converting excess nitrogen to urea which is excreted by the kidneys. Both of these diseases occur in infants; both can have severe outcomes. To that extent they were compatible with the clinical picture of Lakshya. However, this diagnosis was unlikely, as citrullinemia/ argininosuccinic aciduria are not generally associated with acidosis; hence a sample was sent to Japan for evaluation of organic acidemias. The combined results of all analysis were consistent with multiple diagnoses- primary lactic acidosis with organic acidemia, ketosis, and suggested urea cycle disorder.

To meaningfully appreciate Vikas and Poonam’s journey, and their continuing efforts to fight inborn errors of metabolism to this day, we have to make minimal sense of what these medical terms mean. For this we need to delve a little into the biochemical processes in the human body with which these medical conditions are associated. I have attempted to present a simplified version of the scenario below. Our body obtains vital energy for all its functions by the breakdown of glucose which takes place in a regulated, step-wise process. Key steps in this process release energy that is stored in the form of a molecule called ATP and used whenever needed. The first few steps in glucose breakdown take place in a linear cascade and produce a molecule called pyruvate, which has a very central role. Under conditions of low oxygen availability pyruvate is converted to lactate and releases two ATP molecules in the process. However, when oxygen is sufficiently available, pyruvate engages in a more efficient energy-production mechanism. The scene now shifts to the energy factory of the cell called mitochondria. Here the various steps in the pathway move in a cyclic fashion whereby the product of the last reaction becomes the substrate of the first and the cycle becomes self-sustaining. In order to enter this cycle, pyruvate has to get converted into two different molecules, by the action of two different enzymes. The enzyme Pyruvate carboxylase (PC) converts pyruvate to oxaloacetate (OAA), and the enzyme pyruvate dehydrogenase complex (PDC) converts pyruvate to acetyl coenzyme A (CoA). OAA and CoA then react with each other to kickstart the cycle that goes by various names, including Krebs’ cycle after its discoverer Hans Krebs.

Nature is beautifully ingenious. The Krebs’ cycle is not just busy producing energy, it is also inked to protein and fat metabolism. Some of its by products are continually channelled into making amino acids. It also feeds into the urea cycle that removes waste ammonia released from protein breakdown. The Krebs’ cycle is also linked to fat metabolism through CoA. Due to these myriad interconnections, any major perturbation in one step of the cycle can cause a whole host of secondary changes in the levels of different metabolites. This confounds the clinical diagnosis and management of diseases caused by mutations at any single step in the process.

In Part-II of this story we shall see how Vikas and Poonam finally got the correct diagnosis after their third baby was born. The lesson they learnt was that early diagnosis of disease was crucial to save the infant’s life. This journey culminated in Vikas and Poonam being the first parents to resolutely campaign for newborn screening in India so that metabolic disorders could be detected in infants before irreversible damage set in. Early diagnosis saves lives, as relatively simple treatments in the form of special diets or supplements can treat many of the IEMs, and improve the outcome of disease. This part of Vikas and Poonam’s journey shall be the subject of my next blog.

771 views3 comments