Mice with the mutation causing Rett syndrome (middle panel) have an excess of inhibitory connections as compared with normal mice (left panel) and mutated mice reared with no visual stimulation (right panel). Inhibitory connections were also reduced by manipulating the NMDA receptor, restoring a more normal balance of inhibition/excitation.
Research just published in Neuron offers some interesting clues about Rett syndrome, a tragic disease that causes initially healthy girls to lose their ability to speak and to develop motor and respiratory problems. Working with a mouse model, the Boston Children’s Hospital lab of Michela Fagiolini, PhD, explored how the causative mutations, affecting the MECP2 gene, disrupt brain circuitry and function. The team found that the circuit damage can be undone by targeting the NMDA receptor, tipping the brain toward the right balance of inhibition and excitation. They’re now exploring possible pharmaceutical approaches.
The study also suggests that changes in the visual system are a tip-off to what’s going on in the brain as a whole. Full story »
Agustín Cáceres, once a virtual "bubble boy," is no longer on infectious disease precautions.
For the Cáceres family of Argentina, it’s a joyous holiday homecoming. Agustín, who received gene therapy at 5½ months of age, journeyed with his family to Boston for a check-up and got a clean bill of health.
Agustín was born with the rare immune-deficiency disorder SCID-X1. More popularly known as “bubble boy” disease, it left him defenseless against infections, unable to make enough T-cells to fight them off. His baptism was the only time his family could come near him, all wearing masks, gloves and gowns. His infancy was spent in isolation with his mother.
Now, at age 2½, Agustín has been cleared to go to nursery school, ride a bus and attend large family gatherings without fear of contracting a life-threatening infection. When we caught up with him, he was chasing and tumbling with his older brother Jeremías while waiting to bid farewell to his care team. Full story »
Colombian twins Miranda and Olivia Agudelo (with their parents) were the first patients in a clinical trial aimed at making the bone marrow transplant process less toxic.
One thing that most people don’t realize about stem cell transplants (also called bone marrow or hematopoietic stem cell transplants) is that for patients, the transplant itself is probably the easiest part of the process. The grueling part is the preparation for a transplant, called conditioning.
The Complex Care Service makes morning rounds. (L-R: CCS attending physician Melinda Morin, MD; pediatric resident Grant Rowe, MD, PhD; Tracy Allen, nurse practioner, CCS; Kristin Buxton, nurse practitioner, baclofen pump program.)
This is the second post of a two-part series on children with complex medical needs. (Read the first post.) Details on some patients have been changed for privacy reasons.
Led by attending physican Mindy Morin, MD, MBA, the Complex Care Service team starts down the 9th floor hall at Boston Children’s Hospital, pushing a cart carrying a computer and folders full of paperwork. They’ve just spent about an hour discussing each patient; now it’s time for morning rounds on the floor.
All the patients—some children, some adults—have illnesses affecting multiple systems in their body. Many are dependent on ventilators, feeding tubes and other technology. They are seen by physicians from multiple departments at the hospital. Morin and her colleagues provide the glue.
Some patients are asleep, their families off at work; some are attended by families who sleep in the room with them; others are rarely visited. Some smile and blow raspberries, some have limited or no social interaction. In one room, Morin lingers to talk politics with an adult patient who is still seen at Boston Children’s for his congenital condition. Full story »
Afraa Bakhit, from the Middle East, is among the hospital's most complicated patients. Her disorder is unknown.
This is the first post of a two-part series on children with complex medical needs. Details on some patients have been changed for privacy reasons.
This morning, as every morning, the Complex Care Service (CCS) team huddles in a tiny office deep inside Boston Children’s Hospital. They have 14 patients to discuss, each with a mix of problems that involve multiple clinical departments. Many of them are repeat visitors.
The team begins tackling each case in decreasing order of difficulty. “It seems to be the best way to prioritize the patients with the most immediate needs,” says Mindy Morin, MD, MBA, who’s the attending physician this week. Also on the team are two nurse practitioners, a clinical nurse educator and two resident physicians.
Two-year-old Afraa Bakhit from Dubai tops the list for the sheer number of departments consulting on her case: Genetics, Cardiology, Immunology, Infectious Disease, Rheumatology, Pulmonology, Anesthesia and now a specialist from the Vascular Anomalies Center. Full story »
But for a handful of children, it’s the source of one of the most devastating brain infections known—herpes simplex encephalitis (HSE)—causing fever, confusion, personality changes and seizures. If not caught and treated with high-dose antivirals, it’s highly fatal, and even with treatment most children are left with irreversible brain damage.
Why do some children develop HSE while everyone else just shrugs the virus off? Full story »
It’s been more than a decade since the Human Genome Project cracked our genetic code. DNA sequencing is getting cheaper and cheaper. So why isn’t it being used every day in medicine?
The truth is that while we have the technology to blow apart a patient’s DNA and piece it back together, letter by letter, and compare it with normal “reference” DNA, doctors don’t really know what to do with this information. How much of it is really relevant or useful? Should they be giving it back to patients and their families, and how?
Handled badly, the information could do more harm than good. “We don’t want to scare patients for no reason, or for the wrong reason,” says Isaac Kohane, MD, PhD, who chairs the Children’s Hospital Informatics Program.
Seeking a set of best practices for safe, clinically useful genomic sequencing, Boston Children’s Hospital took a crowd-sourcing approach. Full story »
Liam Burns died 12 days after birth from an unexplained set of heart defects. His parents hope the CLARITY challenge will provide a meaningful explanation.
One extended family has a range of unexplained heart defects—sometimes a hole in the heart, sometimes an arrhythmia. One child, Liam Burns, died days after birth from an underdeveloped heart, a narrowed artery to the lungs and an electrical block. Yet other family members have little more than a heart murmur. All of the defects are on the right side of the heart.
Another family’s son, 11-year-old Adam Foye, has unexplained muscle weakness and fatigue. He can walk only short distances and needs a ventilator at night to support his breathing.
These families—and a third that chose to remain anonymous—decided to submit their DNA to a challenge sponsored by Boston Children’s Hospital called CLARITY. Not only have their complete genomes been sequenced, but 30 teams all over the world—from biotech startups to the National Institutes of Health—were given access to the sequences and set loose to come up with “best practices” for interpreting the results. Two dozen turned in submissions, now being evaluated by a panel of judges.Full story »
Trial participant Megan Nighbor (now age 12) in 2008 (courtesy Progeria Research Foundation)
The children came from all over the world: 28 families from 16 countries, speaking over a dozen languages. They faced a grim prognosis: death at an average age of 13 from cardiovascular disease. Not the congenital heart defects we so commonly see in babies coming to Boston Children’s Hospital, but the kind of disease you might find in an 80-year-old: atherosclerosis, heart attacks, strokes.
The children represented three-quarters of the then-known world population with Hutchinson-Gilford Progeria Syndrome, or progeria—a rare, fatal genetic condition in which children seem to age prematurely. When they began arriving at the Clinical Translational Study Unit at Boston Children’s in 2007, most had already lost body fat and hair, had the thin, tight skin typical of elderly people, and were suffering from hearing loss, osteoporosis, hardening of the arteries, stiff joints and failure to grow.
Eosinophilic esophagitis is often misdiagnosed, and seems to be on the rise. (Images: Gretjen Helene Photography)
As an infant, Cameron Ledin sneezed and rubbed his eyes whenever his mother, Kim, nursed him. His growth was slow, and as he got older, it became clear that he had serious feeding problems. When he was old enough for solid foods, he refused to eat. When he was old enough to speak, he complained that eating hurt his stomach.
Over the years, Cameron saw allergy specialists at Boston Children’s Hospital repeatedly, and every visit ended with more confirmed food allergies. By the time he was 7, Cameron could eat only 25 foods, and his pain and symptoms continued. Multiple tests—for airway, pulmonary and upper digestive tract problems—had inconclusive results. Full story »
