A rare chance

By Alison McCook A rare chance Hannah’s swollen belly at 3 weeks Courtesy of Carrie Ostrea Over the course of 5 days last summer, an army of researchers and clinicians examined, poked, and prodded 1-year-old Hannah Ostrea at the National Institutes of Health (NIH). Experts in neurology, rehabilitation medicine, physical therapy, speech pathology, and anesthesiology gave the little girl an EEG, a test of her heart’s electrical activity

By | February 1, 2010

A rare chance

Hannah’s swollen belly at 3 weeks
Courtesy of Carrie Ostrea

Over the course of 5 days last summer, an army of researchers and clinicians examined, poked, and prodded 1-year-old Hannah Ostrea at the National Institutes of Health (NIH). Experts in neurology, rehabilitation medicine, physical therapy, speech pathology, and anesthesiology gave the little girl an EEG, a test of her heart’s electrical activity (EKG), an MRI, a CT scan, X-rays, and a throat exam (laryngoscopy). All this testing was meant not only to help Hannah but in the hope that her rare disease could reveal something about another condition that affects 1 million Americans: Parkinson’s.

Hannah has Gaucher’s disease, and within hours of her birth, it was obvious something was wrong. Looking past her thick head of dark hair, and the fact that she could down an entire bottle of formula in 5 minutes, clinicians quickly saw that her spleen was massive, and her platelet counts were rock bottom. Her liver was expanding—in a few months it looked like she had a volleyball in her stomach. These are the classic signs of Gaucher’s, a rare, recessive genetic disorder in which the body does not produce enough of a lysosomal enzyme that breaks down the fatty substance glucocerebroside, causing it to glob up in cells of the liver, spleen, and other organs—including, sometimes, the brain.

But researchers have never seen the combination of mutations Hannah carries, so doctors couldn’t determine if she had the Type 2 or Type 3 form. Children with Type 2 typically die before their third birthdays, while those with Type 3 can live much longer. “They [wouldn’t] give us a prognosis,” Hannah’s mom, Carrie Ostrea, says. “They came out and said that to us. Which is fine by me.”

Hannah has many classic Gaucher’s symptoms, such as developmental delays, and the inability to easily shift her eyes from side to side or up and down. But she also has some puzzling symptoms. For one, she only blinks once every 30 minutes or so—“you’ll have a staring contest with her,” Ostrea laughs. This is not a symptom of Gaucher’s disease, but it is a symptom of Parkinson’s.

Indeed, in recent years, researchers have been noting more and more crossover between the two diseases, and the hope is that insights into one will reveal secrets of the other.

In an October issue of the New England Journal of Medicine, Ellen Sidransky at the NIH and her colleagues found that Parkinson’s patients were five times more likely to carry a mutation in the gene associated with Gaucher’s disease. Furthermore, Parkinson’s patients with the mutation in the Gaucher’s gene tended to develop Parkinson’s earlier, and were more likely to have family members with Parkinson’s (N Engl J Med, 361:1651–61, 2009). It’s unknown how many people have signs of both diseases, Sidransky notes, but it’s “clearly dozens and dozens.”

Still, Parkinson’s and Gaucher’s are more different than they are alike. One comes from a deficiency of the lysosomal enzyme that breaks down glucocerebroside, the other likely from a deficiency of dopamine, and it’s largely unclear why the two diseases are linked, says Sidransky. Perhaps the lysosome plays a role in Parkinson’s; the protein misfolding that underlies Parkinson’s may be aggravated by mutations in the Gaucher’s gene.

Gaucher’s itself is an interesting model for trying to understand single-gene diseases, Sidransky adds. She and her colleagues like to invite patients with rare presentations of a disease to the NIH to study them and hopefully learn something about an entirely different condition. “I’ve always been convinced that focusing on one thing and becoming an expert helps you see connections” between that one question you’re investigating and other unanswered—perhaps even more significant—questions.

The NIH visits can be long, but Hannah held up fairly well, her mother says. She didn’t like waking up from the EEG and being tied down, and didn’t like the heart ultrasound, but the neuro-ophthalmologist got her to laugh hysterically by turning his video camera around so she could look at herself. “She just thought that was the funniest thing in the world,” Ostrea says.

Comments

Avatar of: Dov Henis

Dov Henis

Posts: 97

February 26, 2010

Inadequate Processing Of Tryptophan/Tyrosine?\n\n\nTwo critical neurotransmitters, serotonin and dopamine,are synthesized from the amino acids tryptophan and tyrosine.\n\nIn the early 50's I proved by dietary experiments (Un of Pgh, Pgh PA) that "crazy chick" was a result of tryptophan deficiency. \n\nMaybe this "rare chance" involves either deficiency or inadequate conversions of tryptophan and/or tyrosine.\n\n\nDov Henis\n\n

February 26, 2010

Both Gaucher's and Parkinson seem to be vitamin D3 deficiency symptoms. \n\nEver tried 5 000 IU vitamin D3 daily to this child? \n\nAdults can tolerate 100 000 IU vitamin D3 daily for at least one year without any side effects. These experiments were done in the 1930ies but seems to be forbidden these days due to supposed but nonexistent toxicity.\n\nBjörn Hammarskjöld\nPediatrician\nPh.D. Biochemistry
Avatar of: anonymous poster

anonymous poster

Posts: 6

February 26, 2010

Thanks Alison. Hope you will post more stories like this.
Avatar of: Susan Freiman

Susan Freiman

Posts: 1

February 26, 2010

Does the ethics committee pass on all the tests being done on this infant?

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