Study ID’s regional differences, diagnosis, care for patients in Spain

Pompe disease is less prevalent than expected, research shows

Andrea Lobo, PhD avatar

by Andrea Lobo, PhD |

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Pompe disease is less prevalent than expected in Spain, at around 3.1 cases per million inhabitants, according to a registry study that identified regional differences in prevalence, as well as the variable diagnosis and care workouts.

“Our data supports the development of agreed guidelines to ensure that the care provided to the patients is standardized across the country,” the researchers wrote in “Description of clinical and genetic features of 122 patients included in the Spanish Pompe registry,” which was published in Neuromuscular Disorders.

Pompe disease is caused by mutations in the GAA gene that lead to no or impaired production of the acid alpha-glucosidase (GAA) enzyme. This causes the sugar molecule glycogen to accumulate that GAA normally breaks down to generate energy, particularly in muscle cells.

Among the types of Pompe, infantile-onset Pompe disease (IOPD) manifests within the first months of life, whereas late-onset Pompe disease (LOPD) is marked by symptoms that appear in childhood or adulthood.

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‘Lower than expected’

There are more than 350 mutations in the GAA gene associated with Pompe disease, but information is limited “about the frequency of these mutations in Spain and whether there are specific variants of the Spanish population,” wrote the researchers, who drew on information from the Spanish Pompe registry from 2013 to 2022 to fill in the blanks. “There is no published data from Spain regarding the existing number of cases, regional distribution, clinical features or, access and response to the treatment.”

The study used data from the first 122 registered patients among 140 people identified. “This represents an estimated prevalence of 3.11 patients per million,” wrote the scientists, who noted the possibility that “some patients with Pompe disease are not included in the study and the estimated prevalence is indeed a bit higher than what has been reported here.”

Most patients had LOPD (113 patients, 92.6%), while nine had IOPD (7.4%). Most were born in the south and southeast regions of Spain. Information about where the parents were born was known in 64 cases, with most born in the same regions.

“Our data suggests that the frequency of the disease in Spain can be probably lower than expected. Taking into account that the estimated population of the country is 45 million, if the prevalence was closer to what has been previously described, this is [one] case per every 60,000 habitants, there should be around 750 patients in total in Spain,” the researchers wrote.

The participants were seen at 29 hospitals in Spain. Most IOPD patients were boys (six, 66.7%) and of African origin (five, 55.6%). Their mean age at diagnosis was close to 5 months, and two were siblings. Two patients died during follow-up.

Participants with LOPD were mainly male (53.1%) and European Caucasian (89.7%). Forty-one patients had relatives affected by the disease, with 36 cases of siblings. Three patients died during follow-up.

Common symptoms in IOPD, LOPD

The most common initial symptom in the IOPD group was reduced muscle tone (four patients). At diagnosis, eight children had increased creatine kinase levels — an indicator of muscle damage — and seven had hypertrophic cardiomyopathy, which happens when the heart becomes enlarged and cannot pump blood properly.

At the last visit, muscle weakness affected mainly the legs, with two using a wheelchair full time. Three had difficulty swallowing — one required tube feeding into the stomach and two needed ventilatory support for breathing.

With LOPD, the most common initial finding was high creatine kinase levels (46.9%), followed by muscle weakness in the legs (36.1%), and respiratory symptoms (6.2%).

A GAA enzyme activity test confirmed the disease in all 22 patients who had results available. Electromyography showed muscle disease in 45 LOPD participants. Seven of 70 patients had heart issues.

During follow-up, most LOPD patients developed leg muscle weakness (63.7%) and eight required a wheelchair. Around half had respiratory symptoms, with 34.5% needing ventilatory support.

Regarding genetic findings, three IOPD children had c.1551+1 G>A mutations in both GAA gene copies. Two of the variants identified — c.956-5_957del and c.1075+2T>C — had never been reported.

Most LOPD patients had the c.-13-32T>G mutation, always in one copy of the GAA gene, combined with a second mutation. Four participants had the same mutation in both GAA copies. The researchers identified 18 previously unreported variants in LOPD.

All IOPD patients received enzyme replacement therapy (ERT), the standard specific approach to treat Pompe disease. Most of the LOPD group (71.6%) also were treated with ERT, most commonly at 20 mg/kg every two weeks (63 patients).

Functional data was available for LOPD patients. Among those treated with ERT who had two or more 6-minute walking tests (6MWTs), results showed a yearly decline in this measure of exercise capacity, regardless of the duration of ERT. Treatment for more than five years was associated with a greater decline. Lung function improved with ERT taken for less than five years, but declined in those treated longer.

“Overall, the Spanish Pompe Registry is a valuable resource for understanding the demographics, patient’s journey and clinical characteristics of patients in Spain,” the researchers said.