Patricia Stallings Case PDF

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The Patricia Stallings Case The place is Hillsboro, Missouri and it’s July 1989.

As described by Rhonda Rigesberger in her article, Justice Denied: "Life seemed perfect and complete for the Stallings family who had just moved to Hillsboro from St Louis to a pretty little white house overlooking Lake Wauwanoka, a large, beautiful, private lake surrounded by a variety of modestly priced and expensive homes.

Patti and David Stallings had moved into their tiny, white, dream house approximately a month before their 3 month old son Ryan became ill and was hospitalised. 'He had my hair and David’s face,' Patti said. 'He had huge dimples and big blue eyes. That was the happiest time of my life. Everything was perfect, everything. A new house, a healthy and happy baby, I mean what could go wrong?'

But everything was about to change for the Stallings. On the evening of July 7, a Friday, Patricia gave Ryan his evening bottle before she put him to bed. He immediately vomited. On Saturday, Ryan seemed to be feeling better so Patricia left him with her husband and went swimming at her sister’s house. She did not become alarmed about Ryan’s condition until Sunday morning when she discovered that he was lethargic, could not keep his food down and his breathing had become laboured. Patti called Children’s Hospital in St Louis and made arrangements to meet a Doctor in the emergency room. She bundled Ryan up and placed him in his car seat but in her agitated state she got lost trying to find Children’s Hospital and ended up at Cardinal Glennon Hospital by mistake." It was to be the biggest mistake of her life!

Cardinal Glennon Hospital St Louis

Initial tests performed on Ryan’s blood at Cardinal Glennon Hospital indicated a severe metabolic acidosis with a blood pH of 7.0 (normal 7.35 – 7.45) and a plasma bicarbonate concentration of 11mM (normal 22 – 26). He was admitted to the paediatric intensive care unit. A toxicological screen on Ryan’s plasma revealed a high level (180 mg/L) of ethylene glycol (radiator antifreeze).

The toxicological analysis was carried out by two laboratories; the Toxicology Department at St Louis University under the direction of Dr Christopher Long and by the independent commercial laboratories of the multinational pharmaceutical company, SmithKline Beecham. Both laboratories reported similar findings. The determination of the ethylene glycol in the plasma was conducted in both laboratories using the reference GC method of Bost and Sunshine as described in the Journal of Analytical Toxicology. By this method, which involves no deproteinisation, extraction or derivatisation, ethylene glycol (EG) has a retention time of about 2.5 minutes.

The GC traces obtained when Ryan Stalling’s plasma was analysed using this method, left no doubt in the minds of the toxicologists, that he had been poisoned with ethylene glycol.

The toxicity of ethylene glycol is due to its stepwise metabolic conversion into oxalic acid, catalysed by alcohol and aldehyde dehydrogenases.

The NADH generated by the alcohol and aldehyde dehydrogenase reactions is reoxidised to NAD+ with the concomitant conversion of pyruvate to lactate,

catalysed by lactate dehydrogenase. The accumulation of lactic acid generates a lactic acidosis while the intermediates in the pathway, glycolaldehyde and glycolic acid together with the final product, oxalic acid have toxic properties of their own. Because of the structural similarity between oxalate and succinate, one effect of oxalic acid is to competitively inhibit the TCA-cycle enzyme succinate dehydrogenase which converts succinate to fumarate in the presence of FAD. COOH COOH

CH2

COOH

CH2 COOH

oxalic acid

succinic acid

The resultant accumulation of acidic TCA cycle intermediates, exacerbates the metabolic acidosis initiated by the lactic acid. Oxalic acid also has the capacity to chelate calcium ions to form insoluble calcium oxalate which can precipitate in the renal tubules and in the brain. This causes kidney damage and central nervous system dysfunction and can also result in hypocalcaemia, or lowered plasma Ca+2 levels. The presence of calcium oxalate in the urine and tissues is an important indicator of ethylene glycol poisoning. The intermediates in the toxic pathway can also interfere with oxidative phosphorylation, DNA, RNA and protein synthesis. Treatment of ethylene glycol poisoning involves preventing the alcohol dehydrogenase-catalysed conversion of the ethylene glycol to glycolaldehyde in the first step of the toxic pathway. Classically this has been achieved by administering ethanol to the patient in an attempt to out compete the ethylene glycol for binding to the active site of the enzyme. More recently, 4methylpyrazole or fomepizole, which inhibits alcohol dehydrogenase has been used with success as an antidote. These measures are only effective, however, if administered soon after the poisoning has occurred. The minimum lethal dose of ethylene glycol is about 100ml and after ingestion death may occur within 24 hours from damage to the central nervous system or more slowly (8-12 days) from renal failure. Somewhat curiously, traces of the xenobiotic ethylene glycol are commonly found in normal blood samples. The ethylene glycol contamination appears to be due to its generation from the ethylene oxide often used in the sterilisation of the plastic syringes employed for blood collection. Ethylene oxide residues in the syringe can hydrolyse to produce small amounts of ethylene glycol when the blood is collected. H2 O CH2

CH2 O

ethylene oxide

CH2 OH

CH2 OH

ethylene glycol (EG)

However, the levels generated in this way are invariably low (2 – 20 mg/L), and far less than the 180mg/L found in Ryan Stallings’ plasma.

As deliberate poisoning with ethylene glycol was suspected, the attending paediatrician, Dr Robert Lynch, called in the Missouri Division of Family Services. Lynch signed an affidavit saying that he suspected poisoning and when Ryan had recovered from the acute episode, the Division of Family Services, having evaluated the family’s social history, took custody of the child. On July 17 th 1989 they placed him in a foster home pending further investigation. Patricia and David Stallings were granted one hour of supervised visitation per week and on September 4th, during one such visit, Patti fed Ryan from a bottle she had brought with her. Four days after this visit, Ryan once again became acutely ill and was rushed to Cardinal Glennon Hospital by the foster parents. This time the metabolic acidosis was even more profound (blood pH = 6.9; plasma bicarbonate concentration 3mM) and he appeared moribund. Again his blood was analysed for ethylene glycol by the same two laboratories. The blood sample, taken 105 hours after Patti Stallings last had access to her son (the visitation bottle feeding), yielded a result so high (911mg/L) that the plasma had to be diluted 10 fold prior to assay.

Once more, a diagnosis of ethylene glycol poisoning was made and he was treated by ethanol infusion. In spite of this, his condition deteriorated and after 3 days, on September 7th, he was declared brain dead. Life support was disconnected and at autopsy, crystalline material assumed to be calcium oxalate was found in Ryan’s kidney and brain tissue.

Just before Ryan’s death, the laboratory of SmithKline Beecham reported that a residue from the baby’s bottle used by Patti Stallings during the visitation feeding had tested “positive for ethylene glycol”.

This was the “smoking gun” the police were looking for to link Patricia Stallings to the crime and the next day a search of the Stallings’ home revealed a half empty container of antifreeze in the basement. Patricia Stallings was arrested on a charge of first degree murder and was remanded in custody without bail, pending trial. Though she was unaware of it, at the time of her arrest, Patricia Stallings was pregnant and 5 months later, in February 1990, she gave birth in jail to her second son, David Jr. Though the baby’s father, David Stallings Sr. was not a suspect in the death of the first child, he was denied custody and David Jr. was immediately placed in foster care. At two months of age, in April 1990, David Jr. became acutely ill and was rushed to Children’s Hospital in St Louis by his foster parents. Significantly, Children’s Hospital to which he was admitted, a specialist paediatric facility, was different from the hospital (Cardinal Glennon) at which his late brother, Ryan, had been diagnosed and treated.

Children's Hospital, St Louis

When admitted, David Jr. was found to be semi-comatose, acutely acidotic and in respiratory distress – signs which had also characterised the illness suffered by Ryan. David Jr., however, was not found to be suffering from ethylene glycol poisoning. Instead, analysis of his blood at Children’s Hospital resulted in the diagnosis of an inborn error of metabolism, methylmalonic acidemia. In this inherited condition, the coenzyme B12-dependent enzyme, methylmalonyl CoA mutase, is defective with the result that methylmalonyl CoA generated from the metabolism of fatty acids with an uneven number of carbons and from the metabolism of the branched chain amino acids, isoleucine and valine, cannot be effectively converted into the TCA cycle intermediate, succinyl CoA. Both methylmalonyl CoA and its immediate precursor, propionyl CoA, accumulate in the tissues which leads to an elevation of the levels of propionic acid and methylmalonic acid in the blood. These compounds are then excreted in the urine.

isoleucine

propionic acid CH3 - CH2 - COOH

methylmalonic acid CH3 - CH - COOH

uneven numbered fatty acids

propionyl CoA CoASH

CO2

methylmalonyl CoA CoASH

methylmalonyl CoA mutase

COOH succinyl CoA

TCA Cycle

Figure 5: Origin of Elevated Levels of Propionic and Methylmalonic Acids in the Plasma of Methylmalonic Acidaemia Patients

The condition has an autosomal recessive inheritance pattern and has an incidence of about 1: 48,000 newborns. In the case of parents such as Patti and David Stallings who are likely to be heterozygous for the condition, each child resulting from the union has a 1 in 4 chance of exhibiting the disease in the homozygous recessive form (aa).

This startling discovery immediately raised questions. Did Ryan Stallings really die from deliberate ethylene glycol poisoning? Could Ryan have been misdiagnosed and might he have succumbed to methylmalonic acidemia instead? After all, as he was David Jr.’s brother, there was a 1 in 4 chance that he too was homozygous for the condition. Two pieces of medical evidence, though, seemed unassailable. First, there was the finding of ethylene glycol in Ryan’s plasma by both SmithKline Beecham and St Louis University. Even if Ryan did suffer from methylmalonic acidemia, this could not account for the levels of ethylene glycol found in his blood. Nor could it account for the autopsy’s finding of apparent calcium oxalate crystals in the child’s brain and other organs; signs consistent with ethylene glycol poisoning. As well as that, traces of ethylene glycol had been found in the bottle Patricia had used to feed Ryan shortly before he was admitted to hospital for the second, and final time. Consequently, the diagnosis of methylmalonic acidemia in Patti Stallings’ second child was deemed inadmissible as evidence in her trial. Ryan, like his brother, may indeed have suffered from the disease but in the view of Circuit Judge Gary P Kramer, that did not preclude poisoning with ethylene glycol. In the courtroom, Jefferson County Prosecuting Attorney, George B McElroy spoke eloquently of a baby’s murder, a mother’s guilt and of a community’s cry for justice. “Don’t speculate that 3-month old Ryan Stallings died of natural causes”, McElroy told the jury. “You might as well speculate that some little man from Mars came down and shot him full of some mysterious bacteria. Don’t try to understand why Patricia Stallings poisoned her child by feeding him from a baby bottle laced with antifreeze,” he told them. “The point is she did it. Only she could have done it,” he said. “Only she would’ve done it.” Ten hours later, jury foreman Delmar Fisher announced to the court that the jury had found Stallings guilty of murder in the first degree and in February 1991, Judge Kramer sentenced her to imprisonment for life without parole. The case was so bizarre that it was soon featured on TVs “Unsolved Mysteries” hosted by Robert Stack.

Two researchers in metabolic diseases at St Louis University, Dr James Shoemaker and Dr William Sly together with Dr Robert Lynch, the paediatrician who attended to Ryan during his first hospital visit, saw the program by chance and were so uneasy about the verdict that they contacted Dr Christopher Long, Head of St Louis University’s Toxicology Department. He was a member of the team that had reported the ethylene glycol in Ryan’s blood. They obtained from him samples of Ryan Stallings’ plasma that had been stored frozen for seven months, and then re-analysed them. Rather than relying on retention times alone, they subjected the suspect GC peak in Ryan’s plasma to mass spectrometry and compared the spectrum obtained with that of an authentic sample of ethylene glycol. An interesting difference emerged:

Ryan's Plasma

The m/z values at 62 and 45 are characteristic of the fragmentation of ethylene glycol CH2 – CH2

CH2 – CH2

OH

OH

OH 62

45

and based on the m/z values, traces of ethylene glycol appeared to be present in the GC peak found in Ryan’s plasma. However, the fragments with m/z values of 74 and 29, together with the high intensity of the fragment at m/z 45 were evidence that another compound was present as well – and was there in much larger amounts. What could it be? Given the possibility that Ryan may have suffered from methylmalonic acidemia, propionic acid was a strong candidate. Propionic acid (MW =74) is similar in size to ethylene glycol and has a comparable volatility. Ethylene Glycol

Propionic Acid CH3

CH2-OH CH2 CH2-OH COOH C2 H6 O2

C3 H6 O2

Using the same GC system and the same method employed by the Toxicology Department at St Louis University when they identified ethylene glycol in Ryan’s plasma, Shoemaker et al. found that ethylene glycol and propionic acid were barely separable from each other. Even under optimal conditions they eluted less than 30 seconds apart. The mass spectrum obtained by Shoemaker et al. for authentic propionic acid confirmed their suspicions. CH3 – CH2 – COOH 74

CH3 – CH2 29

- COOH 45

Spiking experiments provided further proof. Superimposing Ryan Stallings’ GC tracing on that derived from a normal plasma example that had been spiked with ethylene glycol, showed clearly that the peak attributed to ethylene glycol in Ryan’s plasma was distinct (see A below) and it yielded a mass spectrum that identified it, not as ethylene glycol, but as propionic acid. Furthermore, when a sample of Ryan’s plasma was spiked with ethylene glycol, two peaks became evident (see B below). Again, the peak originally ascribed to ethylene glycol was distinct and yielded a mass spectrum typical of propionic acid.

QuickTime™ and a TIFF (Uncom pres sed) decompress or are needed to see this picture.

B Figure. A, Solid line indicates gas chromatographic tracing of proband’s predialysis serum by method of Bost and Sunshine. Dotted line indicates tracing from normal serum spiked with 900 mg ethylene glycol per litre. Serum was stored at room temperature for two weeks and then frozen at -80C, the reported storage history of the proband samples. Peak area was equivalent to 240 mg ethylene glycol per litre. B, Tracings produced as in panel A. Samples of proband’s post dialysis serum. Solid line indicates sample spiked with 25 mg ethylene glycol per litre, but no internal standard (to keep injection volume constant). Dotted line indicates unspiked sample with internal standard. Elution of ethylene glycol was not delayed by presence of acetic acid. Ac, Acetic acid; EG, ethylene glycol; Pr, propionic acid; IS, 200 mg 2,5-hexanedione per litre. (From Shoemaker et al. 1992)

It was clear to Shoemaker et al. that a dreadful mistake had been made. There was no evidence that Ryan Stallings had been poisoned with ethylene glycol at all. The suspicious peak on his plasma GC was due to elevated levels of propionic acid, and not the result of ethylene glycol administration. The small amounts of ethylene glycol found in his plasma could be attributed to contamination from the plastic syringe used to collect the blood. Furthermore, traces of ethylene glycol found in the baby’s bottle could again have been due to contamination resulting from a similar ethylene oxide sterilisation procedure. Ryan Stallings, like his brother David Jr. suffered from methylmalonic acidemia and it is this condition that almost certainly, caused his death. Subsequently, Dr Piero Rinaldo at Yale University confirmed the presence of methylmalonic acid in Ryan’s plasma, a finding that unequivocally established the diagnosis. Not only had Patricia Stallings been wrongly convicted of murder, no murder had been committed! Shoemaker et al. reported their findings to the Jefferson County Prosecuting Attorney’s Office. Patti Stallings conviction was quashed and she was released from prison in September 1991. In spite of this there has been no move to change the cause of death on Ryan Stallings’ death certificate which still reads “homicide by ethylene glycol poisoning”. Dr Phillip Burch, the Deputy Chief Medical Examiner who performed the autopsy on Ryan Stallings and who testified at the Stallings’ trial said, “I signed the autopsy report. I have seen nothing to change my opinion. As far as I am concerned, the child was poisoned to death. The tests were modern, up-todate tests. The diagnosis was fairly definitive.” In a prepared statement, administrators at Cardinal Glennon Hospital said: “Blood drawn at Cardinal Glennon for use in diagnosing the child’s illness was analysed by two outside, highly reputable laboratories. The care provided to the patient by Cardinal Glennon was based on those test results.” St Louis University, where the initial laboratory tests in the Stallings case were performed has officially declined to comment but, unofficially, there are those who believe that the diagnosis of methylmalonic acidemia was incidental. Some still maintain that Ryan Stallings was poisoned with ethylene glycol. They suggest that the low level of ethylene glycol found by Shoemaker et al. reflects the loss of ethylene glycol from the sample by volatilisation during the seven month storage period, and does not necessarily contradict the initial finding. As far as SmithKline Beecham is concerned, Tobey Dichter, a spokeswoman for the company said the laboratory has a policy of not commenting on pending litigation “in fairness to all parties”.

In this respect, the Stallings had filed a wrongful death lawsuit against Cardinal Glennon Hospital, St Louis University, SmithKline Beecham Clinical Laboratories and against several Doctors who participated in Ryan’s care. These claims were subsequently settled out of court for amounts believed to involve millions of dollars. Meanwhile, Patricia and David Stallings say they are still trying to cope with the death of one son and with the disease that threatens the life of another. They have been told his inborn error will be difficult to manage. It will be a long, hard struggle, they say. “We’ve gone through so much, there’s really no use in being angry,” David Stallings said. “It doesn’t do anything but cause trouble. I want the public to know what re...