Maurice Glenn Turner, a police officer inCobb County, Georgia, went to the emergency room on March 2, 1995,complaining of flu-like symptoms.

He was treated there, and when he feltbetter, he went home.

The next morning, he was found dead.

Dr. Brian Frist, the local medical examiner,found nothing abnormal except for leftventricular hypertrophy. He signed Glenn’s death out as “some complication related to an enlarged heart.”

At this point, what is your differentialdiagnosis?

Officer Glenn’s widow Lynn, a 911dispatcher, collected around $153,000 in death benefits.

Within a few days, she leased anapartment with her boyfriend, Forsythcounty sheriff’s deputy Randy Thompson, who later also became a fireman.

They did not marry, but they had a son in 1995 and a daughter in 1998. Fireman Randy insured himself for $200,000.

The relationship ran into problems becauseof Lynn’s extravagant spending habits.Randy moved out and Lynn went into debt.However, he continued to visit her.

On January 21, 2001, Randy went to theemergency room for a severe stomach-ache and vomiting. He was treated andreleased.

Lynn made Randy some green Jell-Oto help him settle his stomach.

The next morning, he was found dead.

Dr. Mark Koponen, the local medical examiner could find nothing wrong except for some crystals in the kidneys and some coronary artery atherosclerosis.

He signed it out as sudden coronary death.

At this point, what is your differentialdiagnosis?

Fireman Randy’s girlfriend Lynn collected around $36,000 in death benefits.

Officer Glenn’s mother read about FiremanRandy’s death in the newspaper. Shecontacted Fireman Randy’s mother. Bothfamilies felt that something was not right.

They talked with Dr. Koponen, who sentblood and urine to forensic toxicologist Chris Tilson.

Blood samples are routinely testedby several methods, includinggas chromatography, which picksup voltaile acids and alcohols.

Dr. Tilson found ethylene glycol, butnot in quantities sufficient to cause death.He sent more samples to National Medical Services, a forensic reference lab.

NMS found toxic levels of ethylene glycol.Dr. Koponen changed the cause of deathto ethylene glycol poisoning.

Dr. Frist exhumed Officer Glenn and foundlethal levels of ethylene glycol as well.

Julia Lynn Turner was indicted forOfficer Glenn’s murder in 2001, and stoodtrial in May, 2004.

A veterinary nurse described how Lynnhad asked her in detail about the effectsof antifreeze on cats.

Other witnesses testified that she said sheonly cared about the insurance money,and that Officer Glenn had remarked thathe was afraid she would try to kill him.

The jury also heard about FiremanRandy’s cause of death.

Toxicologist Chris Tilson explained his own error – a misplaced decimal point.

Manufacturers testified that theirembalming fluids did not containethylene glycol, thereby refuting thedefense’s only real argument.

Dr. Kris Sperry, the chief medical examinerfor the Georgia Bureau of Investigation,made the clinical correlations.

Dr. Frist, the original medical examiner,described some experiments that he haddone. Lime Jell-O and Gator-Ade can belaced with ethylene glycol withoutsignificantly changing the look or taste.

Lynn was found guilty of murdering Officer Glenn with malice. She got lifein prison.

Ethylene Glycol

Because of its low molecular weightand the fact that it will not boil off,ethylene glycol is a superb antifreeze.

It is odorless, colorless,and sweet-tasting.

Fluorescein is added to antifreeze in the US, and it will appear in the urine if ethylene glycol has been ingested, alerting doctors.

Around 90,000 animals and 4000 humansingest ethylene glycol each year in the US.

Here, Mark Trail’s dog Andy is showndiscovering a pool of antifreeze.

The problems develop when the moleculeis metabolized to the three potent acids –glycolic acid, glyoxylic acid, and oxalic acid.

Calcium oxalate crystals are familiar, andin ethylene glycol poisoning, they cause renal damage and appear in the urine.

Here’s a touch prep from the kidney of adog that died of ethylene glycol poisoning.

The crystals are birefringent.

It is probably these crystals that do themechanical damage to brain and kidney.

Always take a moment to calculate theanion gap. By custom, Na – Cl – HCO3

Normal range is 8-16 mEq/L

Anion gap above 16 mEq/L?

Remember:

ketoacidosislactic acidosis (shock / exertion)aspirin poisoningethylene glycol poisoninguremiaisopropanol, isoniazid, other Rx’scertain uncommon metabolic illnesses

Treating ethylene glycol poisoning:

SupportBicarbonateEthanol (slows metabolism)Dialysis

How do you do it?

There have been other instances ofcriminal poisonings.

On July 7, 2004, Maryann Neabor, anemergency medical technician, fatallypoisoned her former brother-in-lawwith ethylene glycol in pineapple juice.

James Keown, a Jefferson City, Missouri,radio personality, was arrested on the airin 2005.

He is charged with chronically poisoninghis wife, Julie, for her insurance money.

In 2004, Maureen Plambeck was chargedwith poisoning her former sister-in-lawwith antifreeze in Margarita mix.

The victim recovered. The defense wasthat she was trying to save the life ofanother family member.

Scooby was a golden retriever inAlbuquerque who was maliciouslypoisoned with ethylene glycol.

Scooby got his due in April 2005, whenNew Mexico joined California andOregon in mandating that a bitter-tastingcompound be added to antifreeze.

Two ethylene glycol molecules linkedas an ether is diethylene glycol.

This is a sweet, syrupy liquid that issomewhat less toxic than ethylene glycol,but still not good to ingest. Exactlyhow it does damage remains unknown.

Diethylene glycol is the main ingredientin “Sterno.”

It was the deadlyingredient in the 1938 sulfanilamide disaster in the US…

Raspberry flavorUnfortunately, delicious

… and the 1995-6 Haitian acetaminophencatastrophe.

In 1985, some Austrian winemakersturned “dry” wine to “sweet” wine byadding diethylene glycol.

One would have had to drink two bottlesdaily for a week to get sick, but this wasstill bad business. Regulations followed.

This tale gave rise to the urban legendthat the French had put antifreeze in wine. An 1990 episode of “The Simpsons” commemorated this.

The Crepesof Wrath

Bart became a hero for exposing a plotby French winemakers to add antifreezeto their wine.

“Sierra” is propylene glycol. Much lesstoxic, but more expensive, it appeals tomotorists who are concerned about animals.

It’s also notquite so goodan antifreeze.

Why not?

Okay.

There’s more.

Ryan Stallings:

Three month old white male broughtto Children’s Hospital, St. Louis, July 1989

1 day history of feeding intolerancefollowed by increased lethargy andtachypnea

In the CardinalGlennonChildren’sER, Ryan wasfound to havepH 7.02Anion gap 26.3Bicarb 3 mMol/LKetonuria

At this point, what is your differentialdiagnosis?

On the second hospital day, St. Louis U’stoxicology lab reported:

Serum Acetone 3700 umol/L= 215 mg/L

Blood Ethylene 180 mg/L Glycol

Smith Kline Beecham, an independentlab, confirmed the presence of deadlylevels of ethylene glycol.

Your lecturer led the College of AmericanPathologists’ team that did this lab’sinspection a few years ago.

Ryan improved, but continued to belethargic and to feed poorly.

The physicians believed the child hadbeen poisoned, and he was placed ina foster home.

On September 1, Ryan’s mother Patriciawas allowed a supervised visit, and fedhim with a bottle.

On September 4, Ryan was hospitalizedagain, with lethargy, muscle spasms, andhyperventilation. His pH was 6.9.

He was treated with IV ethanol, but diedsoon afterwards. St. Louis Hospital’s lab found 119 mg/L of ethylene glycol in hisblood. Smith-Kline confirmed this by gas chromatography.

St. Louis also reported that “traces of ethylene glycol” were found on the bottle.

Patricia Stallings was arrested for murder.

Patricia Stallings spent the next seven months in jail, and then gave birth toa second son, David Jr., who was put in foster care.

Within two weeks, David became acidoticand unresponsive, and was hospitalized.He was found almost at once to havevitamin B12-unresponsive methylmalonicacidemia.

Methylmalonyl-CoA mutase is requiredto transform L-methylmalonyl-CoA intosuccinyl-CoA.

If the enzymeis missing…

Methylmalonic acid is elevated in theblood…

… as is propionic acid (its decarboxylationproduct) and its various secondarymetabolites.

Of course, there was talk about alab error and a death from a metabolicdisorder. The state did its homework.

Before the trial, the prosecutor actuallyasked Dr. Christopher Long to turnover a sample of Ryan’s blood to thelocal subspecialty lab.

Dr. James Shoemaker, who ran the lab,found a large amount of methylmalonicacid, plus traces of ethylene glycol.

Dr. Shoemaker presented this informationat a conference. The team decided thatlittle Ryan probably did indeed havemethylmalonic acidemia.

But they concluded that it was stillethylene glycol poisoning, because of thecrystals in the brain and the presence ofethylene glycol in the bottle. They had theidea that the ethylene glycol in Ryan’s blood had “dissipated” in storage.

Patricia Stalling’s lawyer did not attempt to obtain any expert support for the idea thatRyan’s death was not due to ethyleneglycol poisoning.

Patricia Stallings was convicted of murder.

“Unsolved Mysteries” got ahold of thecase. Dr. William Sly, chief of Biochemistryat SLU, watched the show and gottogether with Dr. Shoemaker.

They went back to the specimens, and used a more sophisticated technique…

… coupling a Hewlett-Packard 5890gas chromatograph …

… to a VG mass spectrometer.

Gas chromatography….

Solid line is Ryan StallingsDotted line is normal serum + 900 mg/L ethylene glycol

Gas chromatography….

Solid line is Ryan Stallings spiked with ethylene glycol, no ISDotted line is Ryan Stallings with internal standard

Mass spectrum for ethylene glycol

Mass spectrum for propionic acid

The two fragmentationpatterns are notat all similar.

There was actually NO ethylene glycol inthe blood. The old gas chromatographtechnique mistook propionic acidfor ethylene glycol.

Huge amounts of propionic acid,plus methylmalonic, acetic, hydroxybutyric, and -hydroxyisovaleric acids provedthe diagnosis of methylmalonic acidemia.

The prosecutor still could not explainthe crystals in the brain. He contactedYale’s Piero Rinaldo, who knew theanswer.

Everybody had overlooked the obvious.Babies metabolize big doses of ethanolinto oxalic acid.

The “ethylene glycol” on the bottle turnedout to be residue from the ethyleneoxide used to sterilize collection equipment.

In an unprecedented move, the prosecutorasked the judge to declare trial counselincompetent, and order a new trial.The prosecutor then dropped the charges,and Patricia Stallings was freed.

Okay.

There’s more.

A previously healthy 6 month old girlwas admitted to a community hospital.Mother had noted decreased activity,increased irritability, poor feeding, anddecreased urination over 3 days. On theday of admission, the child had begunto vomit and become lethargic, pale,tachypneic, and hypotonic.

Admitting labs:

pH 7.12pCO2 12 torrpO2 320 torrBicarb 4 mmol/LAnion gap 24UA: 100-120 rbc/hpf, 3-8 wbc/hpf

Tox screen did not show ethylene glycol.

At this point, what is your differentialdiagnosis?

The community hospital sent the childto Mass General, where the anion gapand all the other abnormal labs werenormal by the next day. All cultures werenegative.

The blood showed a very high level ofglycine. Urine contained traces of threedicarboxylic acids (adipic, suberic,and octenedioic).

The folks at Mass General were much tooclever to fall into the trap of assuming thiswas ethylene glycol poisoning.

They expected that with the Stallingsfiasco, there would be no faulty reportingabout ethylene glycol! They decidedthis must be another curious genetic disorder causing a metabolic acidosis,perhaps one that had never been reported.

They decided to “wait and see.”

Six days later, the child was back at thecommunity hospital with the same symptoms. pH was 7.18, bicarbonate was7, and anion gap was 28. The childwas given bicarbonate and sent back toMass General, where everything rapidlyreverted to normal.

Despite a lot of assays, all turning out normal, the Mass General team decided she had some disorder of fatty acid metabolism, and placed her on a low-fat diet.

Two months later, she was back at thecommunity hospital with the same abrupt onset of the same symptoms andlab findings.

This time, she was transferred to Children’s in Boston.

Children’s checked the urine for organicacids. It was loaded with glycolic acidand some unidentified peaks. Blood glycine was three times normal.

Serum collected on the day of admissionturned out to containhigh levels ofethylene glycol.Really.

It turned out that, unbeknownst to thecommunity hospital and Mass General,the toxicology screens did not includeethylene glycol among the substancesfor which they searched.

The district attorney and social servicespeople investigated. The parents firedthe baby-sitter “whose work scheduleparalleled the onset of illness.”

A bottle of infant formula in the refrigeratorcontained 220 mg/dL of ethylene glycol.There was none in the lot of formula from which this had been obtained.

The child has had no sequelae.

What did we learn?