Hunter syndrome affects 13 boys in a million. Here’s how to recognize it
Leading specialist Dr. Chris Hendriksz takes healthcare professionals through a step-by-step guide to the disease
A 3-year-old male patient is brought to his primary care provider with concerns about his development. He is not speaking, can walk only a few steps, and has been acting erratically and aggressively. Although at birth he appeared normal, he now exhibits enlargement of the skull, earlobes, tongue, and nostrils.
This patient has Hunter syndrome, an extremely rare genetic disorder also known as mucopolysaccharidosis type II (MPS 2). Hunter Syndrome causes developmental delay, dysmorphism, and early mortality. The most important thing a clinician can do is recognize the signs of the disease and refer a patient for further evaluation.
Like most rare diseases, the diagnostic journey for patients is typically long and frustrating. Rare-disease patients see an average of seven specialists before being correctly diagnosed. Grand Rounds are designed to address this problem by introducing the more than 1 million healthcare professionals on the Figure 1 platform to rare conditions like Hunter syndrome.
Here are five highlights — the questions asked, the examples shared, and the lessons learned — from Dr. Hendriksz’s one-hour Grand Rounds on Figure 1:
1. “The one thing that will keep you humble in rare diseases is the amount of times you will predict the prognosis incorrectly.”
In response to a pediatrician who asked how soon the severity of the disease can be detected, Dr. Hendriksz said, “I suspect you are trying to ask when can we distinguish between those with CNS disease and those without, and in general around the age of about 6 you are able to distinguish between the 2 groups.”
But as he then noted, “the one thing that will keep you humble in rare diseases is the amount of times you will predict the prognosis incorrectly. So my advice is not to be too dogmatic and leave some hope for all families as life is unsure for all of us.”
2. “My question about Hunter’s is: why is their survival age only into the 20s?”
“Sadly this is a progressive disorder and progressive accumulation of storage material in the brain, heart and airways are the main causes of death,” Dr. Hendriksz responded. “Brain involvement lead to loss of skills like safe swallowing which leads to aspiration and infections leading to death. Respiratory failure due to obstructive airways disease and cardiac disease is combination of valve disease and arrhythmias.”
3. Why nearly every patient is male
Hunter syndrome is a rare, X-linked disease, which means nearly every patient is male. The incidence of the disease is 1.3/100,000 live male births. The disease appears to be equally distributed racially and geographically.
4. The nuances of mandatory screening
“Would you see value in mandatory newborn screening for Hunter syndrome or other rare conditions?” a nurse practitioner asked.
“Newborn screening depends on what you want to achieve with the result,” Dr. Hendriksz responded, “and that will differ from country to country and influenced by cultural, religious, financial and political factors even before you involve patient choice.
“It is fascinating that when you speak to doctors and families who have been affected by rare disorders, they would universally support newborn screening as they will have walked that difficult road … ”
“If you speak to the general population then you will find that many will feel that screening may be detrimental to early bonding with the child, early medicalization or false positive which are the worst. You are forgiven for the false negatives more than the false positives.”
5. Early detection is critical.
Detailed medical and family histories lend important clues, as Hunter syndrome comprises a constellation of seemingly unrelated conditions. A combination of macrocephaly and facial dysmorphia, developmental delays, and chronic upper respiratory tract infections, including otitis media, should prompt immediate referral to a geneticist.
Find out more about Hunter syndrome in the Figure 1 Grand Rounds.
References:
Wraith JE, Bodamer OA, Guffon N, Malm G. Mucopolysaccharidosis type II (Hunter syndrome): a clinical review and recommendations for treatment in the area of enzyme replacement therapy. Eur J Pediatr 2008;167:267–77.
Engel PA, Bagal S, Broback M, Boice N. Physician and patient perceptions regarding physician training in rare diseases: the need for stronger educational initiatives for physicians. Journal of Rare Disorders 2013: Vol. 1, Issue 2. Available at http://www.journalofraredisorders.com/pub/IssuePDFs/Engel.pdf Last accessed 12/14/2016.
Pletcher BA, Toriell HV, Noblin SJ, Seaver LH, Driscoll DA, Bennett RL, Gross SJ. Indications for genetic referral: a guide for healthcare providers. Genet Med; 9(6):385–9.
This content was developed in partnership with Shire. Dr. Hendriksz is a paid consultant for Shire.
