Obstructive Sleep Apnea Not More Severe or Frequent in Patients with Mild Fabry Disease, Study Says

Patients with mild Fabry disease do not have a higher prevalence or severity of obstructive sleep apnea when compared with the general population, a study suggests.

However, these patients experience more daytime sleepiness and more airflow blockages during sleep, and any of these problems is severe enough to be clinically meaningful, or can account for their reduced quality of life, researchers say.

Their study, “Obstructive sleep apnea and quality of life in Fabry disease: a prospective parallel cohort study,” was published in the journal Sleep and Breathing.

Many studies have suggested that patients with Fabry disease have a reduced quality of life, and excessive daytime sleepiness is the most commonly reported symptom by more than two-thirds of these patients.

In fact, sleep disorders and, in particular, obstructive sleep apnea (OSA), seem to be common in this population. OSA is a potentially serious condition, where breathing repeatedly stops and restarts during sleep. It occurs when throat muscles relax from time to time and block the airways during sleep.

As OSA is also frequent in the general population, it remains unclear whether this problem is more prevalent in Fabry patients and how much it affects patients’ quality of life.

Therefore, researchers at University Hospital Zurich conducted a large study where they measured the prevalence of OSA in 52 patients with Fabry disease and compared it with 104 healthy controls matched for sex, age, and body mass index.

Their hypothesis was that OSA is more prevalent in individuals with Fabry disease “and contributes to the high burden of excessive daytime sleepiness and impaired quality of life in patients,” they said.

Researchers assessed daytime sleepiness, Fabry severity, and quality of life using patient-reported scales. Every participant underwent overnight monitoring of partial (hypopnea) or complete (apnea) blockage of the airflow, drops in oxygen saturation, and snoring events.

OSA was diagnosed based on the frequency of hypopnea and apnea episodes.

Most patients had mild symptoms and signs of disease activity, and 32 were being treated with Fabrazyme, an enzyme replacement therapy.

The results showed that Fabry patients had double the number of apneas and hypopneas per hour of sleep, compared with healthy controls. However, because OSA severity (defined as apneas and hypopneas per hour sleep) differed little between the two groups (a variation of 0.3 events per hour), “this finding is clinically not significant,” the researchers noted.

In addition, OSA tended to be more prevalent in Fabry patients (19.2%) than in the healthy group (9.0%) but this finding was not statistically significant.

In Fabry patients, hypopneas were the most common respiratory events (66%), followed by obstructive (30%) and central apneas (4%). Central sleep apneas occur because the brain stops sending the appropriate signals to the muscles that control breathing.

It was not possible to estimate the precise impact of OSA prevalence on the quality of life of these patients due to the small sample size. However, “a clear detrimental impact of FD on quality of life was noted,” the researchers wrote, and this impact seems to extend far beyond the influence of OSA alone.

Thus, the researchers argued that “although adequate treatment for OSA effectively contributes to improved quality of life, OSA treatment may only have moderate effects on quality of life in patients with FD.”

Consistent with prior reports, patients with Fabry disease reported significantly higher daytime sleepiness. However, this difference “was modest and most likely smaller than the minimum clinically relevant difference,” the researchers said.

A small porportion of study participants reported excessive daytime sleepiness, which may stem from the fact that disease activity was generally low in this patient sample.

Different causes of sleep apnea in Fabry patients have been proposed, including the presence of narrower airways. Some studies also suggest that central sleep apnea, rather than OSA, is the underlying cause for excessive daytime sleepiness.

Future studies employing polysomnography — the gold standard for diagnosing OSA — would be helpful to understand the underlying causes of obstructive sleep apnea in this patient population. 

“Clinical trials are ultimately needed to assess the effect of OSA treatment and symptoms in patients with FD,” the researchers concluded.