Late-onset Pompe Patient Gave Birth Twice to Healthy Infants While on Lumizyme, Case Study Reports

A woman with late-onset Pompe disease went through two successful pregnancies and births while continuing treatment with Lumizyme (alglucosidase alfa), a case study reports. The woman, however, chose not to breastfeed the infants.

The study, “Two successfully completed pregnancies in adult onset Pompe disease, under continued treatment with alglucosidase alfa,” was published in the journal Acta Neurologica Belgica.

Late-onset Pompe disease usually presents in late childhood, adolescence or adulthood. These patients have higher levels of the alpha-glucosidase enzyme than those with infantile-onset disease, but these levels are still lower than normal. Treatment with Sanofi Genzyme’s Lumizyme (Myozyme in Europe), the only enzyme replacement therapy (ERT) for Pompe disease patients in the U.S., is intended to normalize the enzyme’s levels and slow the progressive muscle weakness in these patients.

Given the limited data on ERT safety during pregnancy and lactation, this treatment is stopped in most reported cases of pregnancy and delivery in women with Pompe disease. In contrast, the scientists from Ghent University Hospital, in Belgium, described a 26-year-old woman with late-onset Pompe disease, who had two successful pregnancies while on Lumizyme.

During childhood, the patient had experienced less strength and more frequent falls than other children of her age. She was diagnosed with late-onset Pompe disease at age 15 after years of complaining from poor muscle strength and muscle pain, especially in the abdomen. At diagnosis, she experienced limb-girdle muscle weakness (hip and shoulder areas) more pronounced in her lower than upper limbs.

Genetic testing revealed compound heterozygous mutations (two different mutations in the gene copies) in the GAA gene, which codes for alpha-glucosidase. Treatment with Lumizyme was initiated nine months after her diagnosis, and she continued since with intravenous infusions every two weeks.

The patient’s motor function — assessed twice per year — showed gradual improvement over the first years of treatment, although with occasional variability. Her forced vital capacity — a measure of lung function, also checked every six months — was 93% before starting Lumizyme and remained stable throughout treatment.

She became pregnant for the first time at age 21, choosing to continue with the therapy to prevent clinical worsening. No relevant complications occurred, although a slight progression of Pompe disease was noted, with mild deterioration of motor and pulmonary function.

A baby girl was born after 38 weeks of pregnancy through normal vaginal delivery. The baby’s Apgar scores — a measure of heart rate, muscle tone, reflexes, skin color, and breathing — were 7/10 at one minute and 8/10 at five minutes after birth, indicating good health. Her body weight was normal. The woman chose not to breastfeed her daughter due to her continuing treatment with Lumizyme.

At 24, she became pregnant for the second time, again deciding to continue with the ERT. Similar to the first pregnancy, her lung and motor function worsened slightly during pregnancy, “but this effect seems to be less pronounced than expected,” the medical team noted.

A baby boy was born after 37 weeks of pregnancy, also though a normal vaginal delivery. His body weight and Apgar score at one minute (9/10) were normal. Again, the patient chose not to breastfeed.

Both children had no notable health problems in the first years of life and were doing well.

“Our observations are reassuring for both the treating neurologists and the patients,” the team wrote.

The scientists cautioned, however, that one successful case is not enough to demonstrate the degree of protection against severe disease worsening provided by continuing treatment with Lumizyme during pregnancy. Further studies of ERT efficacy and safety in these patients are needed, they said.