Beyond the amyloid hypothesis: proteins that indicate cognitive stability

If you’re wondering where Alzheimer’s research might be headed after the latest large-scale failure of a clinical trial based on the “amyloid hypothesis,” check this Read more

Mother's milk is OK, even for the in-between babies

“Stop feeding him milk right away – just to be safe” was not what a new mother wanted to hear. The call came several days after Tamara Caspary gave birth to fraternal twins, a boy and a girl. She and husband David Katz were in the period of wonder and panic, both recovering and figuring out how to care for them. “A nurse called to ask how my son was doing,” says Caspary, a developmental Read more

Focus on mitochondria in schizophrenia research

Despite advances in genomics in recent years, schizophrenia remains one of the most complex challenges of both genetics and neuroscience. The chromosomal abnormality 22q11 deletion syndrome, also known as DiGeorge syndrome, offers a way in, since it is one of the strongest genetic risk factors for schizophrenia. Out of dozens of genes within the 22q11 deletion, several encode proteins found in mitochondria. A team of Emory scientists, led by cell biologist Victor Faundez, recently analyzed Read more

metabolic disorders

Genomics plus human intelligence

Emory geneticists Hong Li and Michael Gambello recently identified the first pediatric case of a rare inherited metabolic disorder: glucagon receptor deficiency. Their findings, published in Molecular Genetics and Metabolic Reports, show the power of gene sequencing to solve puzzles – when combined with human intelligence. Although the diagnosis did not resolve all the issues faced by the patient, it allowed doctors to advise the family about diet and possible pancreatic tumor risk.

The family of a now 9-year-old girl came to Li when the girl was 4 years old. Based on newborn screening, the girl had been diagnosed with a known disorder called arginase deficiency. Arginase breaks down the amino acid arginine; if it is deficient, arginine and toxic ammonia tend to accumulate. At birth, the girl had high arginine levels – hence the initial diagnosis.

The girl had a history of low body weight, anorexia and intermittent vomiting, which led doctors to place a feeding tube through the abdominal wall into her stomach. For several years, she was given a special low-protein liquid diet and supplements, aimed at heading off nutritional imbalance and tissue breakdown. However, she did not have intellectual disability or neurological symptoms, which are often seen with arginase deficiency.

In fact, her blood amino acids, including arginine, were fully normalized, and a genetic test for arginase deficiency was normal as well.  These results were perplexing. By reviewing all the clinical, biochemical and molecular data, Li concluded the girl did not have arginase deficiency, and began looking for an alternative diagnosis. Read more

Posted on by Quinn Eastman in Uncategorized Leave a comment

Emory med student makes early-career contribution on inherited metabolic disorder

Medical student Colin O’Shea is the first author on a paper published May 21 in the journal Pediatrics. Before beginning medical school, O’Shea worked at the National Human Genome Research Institute, part of the National Institutes of Health.

He was working with Charles Venditti, MD, PhD, a leading researcher at NHGRI studying methylmalonic acidemia(MMA) MMA is an inherited metabolic disorder in which the body can’t break down certain amino acids and fats, leading to a buildup of methymalonic acid and ammonia.

The NHGRI has a more detailed description of this research HERE.

Medical student Colin O'Shea

Infants with MMA can have developmental delays, recurrent vomiting and seizures. The disease can be detected through metabolic screening for newborns, and a low-protein diet combined with dietary supplements can help manage the disease.

O’Shea’s research could give parents a better idea of what to expect, and give doctors clues for warning signs when monitoring a patient’s progress. His paper represents the largest study (43 individuals, over six years) so far of the cognitive and neurological status of people with MMA. He worked with a team of psychologists, clinicians and radiologists at the National Institutes of Health to compile information on participants. The ages at which the participants in the study were evaluated ranged from 2 to 32.

“Colin worked hard to make this happen, and I think the larger point is that students at the beginning of their careers can really make an impact,” says Venditti.

The data shows that the IQ scores of people with MMA vary quite a bit (the mean is around 85), with seizures and high ammonia levels being predictors of lower scores. O’Shea’s team found that the IQ scores of people with MMA tend to be lower than neurotypical individuals, but their scores are generally stable and cognitive decline is not a necessary feature of the disease. On neurocognitive tests, people with MMA do appear to have a particular deficit in processing speed. O’Shea, Venditti and their colleagues write that this finding was “particularly striking” and it may reflect damage to the part of the brain known as the basal ganglia.

“I am excited by the prospect of continuing to work in the field of inherited disorders,” O’Shea says. “That said, Emory has opened up many
doors to me with regard to future careers. I’ve enjoyed almost every subject I’ve been taught thus far, so I’m still deciding what path I’d
like to choose.”

Posted on by Quinn Eastman in Uncategorized Leave a comment