Calories Sugar Cookie

Dr. " House or Dr. House?

By Lionel Perez Valenzuela

Questions with answers

Sometimes our students, we ask:

- Do I need to know chemistry to be a doctor or biologist?

- In what shall it profit a doctor to know the metabolic pathways?

One possible answer might be:

- Yes, absolutely, to save the lives of your patients and not to send their parents to jail, and these completely innocent.

But what kind of response is this?

Only one of the many possible.

A diagnostic error

Stalling In 1989 Patricia takes her 3 month old son, Ryan, to the emergency room at Cardinal Glennon Children's Hospital of St. Louis . The child, a very serious picture, difficulty breathing, uncontrollable vomiting and gastric problems. The doctor handler, a toxicologist, examine the child and concluded that their symptoms are the result of poisoning by ethylene glycol (antifreeze additive very common). These suspicions were confirmed by the hospital laboratory and a private laboratory, independently.

After his recovery, the child was sent to a family foster care . The parents were allowed supervised visits. In one of these visits, parents were a moment alone with the baby, and after that the child is out of kilter and died.

The parents were charged with first degree murder. The first analysis of the child's blood showed the presence of large amounts of ethylene and traces in the bottle with which the mother had fed her son during the visit.

Patricia Stalling already in prison, she realized she was pregnant. She and her husband had done a great experiment. In February 1990 his second son was born to David Stalling was taken into custody with a foster family. But the few weeks showed the same symptoms as her brother died. The diagnosis was methyl malonic acidemia. A disease that has symptoms that of ethylene glycol poisoning. Despite the prosecution rejected this new defense arguments and the mother was convicted, as it was considered proven by blood and bottle of ethylene glycol poisoning.

seemed a done deal, but ...

What is methyl malonic acidemia?

is an inborn error of metabolism. Are borne diseases to occur in a gene mutation that alters the genetic makeup of a person, disrupting its normal functions, leading to a physiological disorder that causes the following problems:

1. No synthesis of a compound essential for the organism.

2. Accumulation of toxic intermediate compounds to the CNS.

3. Accumulation of compounds that cause cell damage that occurs.

4. Stimulation of alternative routes to production unwanted substances.

In a more detailed description, methyl malonic acidemia (found methyl malonic acid in the blood) is an inherited, autosomal recessive, caused by a defect in the enzyme methyl malonyl CoA mutase (MCM). This enzyme is necessary for the metabolism of certain amino acids (isoleucine, valine, threonine and methionine), cholesterol and certain fatty acids. When proteins are degraded, these amino acids can be converted into methylmalonyl CoA, thanks to the MCM succinyl CoA can become an intermediary in the Krebs Cycle. Thus these amino acids enter the pathways that can supply energy to the cell. When the MCM is mutated, the malonyl CoA can not be converted to succinyl CoA and accumulates in blood and urine as methyl malonic acid. Causing seizures, paralysis, kidney damage and liver, impaired growth, mental retardation and ultimately death. The disease occurs in approximately one of 48,000 births, in its various forms. Since 1985 there is a treatment ( L-carnitine and metronidazole) , allowing children who survive the first attacks, cope with a relatively normal life.

Does television saves lives?

After hearing about the case of Mrs. Stalling on a television show, William Slay, head of Molecular Biology and James Shoemaker lab chief metabolic studies University of St. Louis, began investigating this case. Working alongside them Piero Rinaldo an expert in metabolic diseases of the school of medicine at Yale University.

As a first step decided to analyze the blood of Ryan. They found large amounts of methyl malonic acid and no ethylene glycol, the poison allegedly used. They also found huge concentrations of ketone bodies and methyl malonic acid in urine, something completely line with methylmalonic aciduria.

The bottle could not be tested because he disappeared mysteriously.

These results differed from those previously conducted analysis. Further investigation revealed that the hospital lab not respect their own protocols. Since the profile of blood samples from Ryan did not match the standard samples with ethylene glycol used by the hospital. Despite this the hospital laboratory said it had found ethylene glycol in the patient's blood. Moreover, the private laboratory detected an unusual molecule in the blood of Ryan, but not correctly identified, mistook the peak detection of methylmalonic acid in the HPLC (High Performance Liquid Chromatography), assuming that was ethylene glycol. also determined that although they had found nothing unusual in the samples of the bottle argued the presence of ethylene glycol.

After these findings, Patricia Stalling, was acquitted of all charges.

This is a dramatic demonstration that a proper diagnosis can save patients with rare metabolic diseases. A proper understanding of metabolic pathways and inborn errors of metabolism, is necessary for diagnosis and management, proper and immediate.

What is newborn metabolic screening?

are laboratory tests to detect inborn diseases with alterations in biochemical processes or birth.

Worldwide experience has shown that 20-30% of cases of pediatric hospital mortality, is based on a disease genetics.

should be an evaluation of the babies 2 to 8 days old. Up to 6 months of age. Keep in mind that babies with this disease usually appear completely normal and no symptoms initially. From there, the importance of conducting these studies and to further improve the early detection and treatment of metabolic diseases.