The discovery of a new combination of mutations causing infantile-onset Pompe disease, described in a case report, highlights the importance of screening for early detection of the rare genetic disorder.
A sensitive and inexpensive screening system could improve the prognosis of infants with Pompe disease (PD), the researchers said.
The case report, “The Novel Compound Heterozygous Mutations of GAA Gene in Mainland Chinese Patient with Classic Infantile-Onset Pompe Disease,” was published in the International Heart Journal.
Pompe is caused by mutations in the GAA gene, which provides instructions for making an enzyme called acid alpha-glucosidase (GAA). That enzyme normally breaks down a complex sugar called glycogen into a simpler sugar called glucose. Glucose is the main energy source for most cells.
Infantile-onset Pompe disease, or IOPD, is — as its name suggests — a form of the disorder in which patients start experiencing their first symptoms during infancy. In classic IOPD, symptoms usually manifest during the first year of life.
This new report describes the case of a girl in mainland China who, at the age of four months and 14 days, was taken to the hospital because of a bluish skin discoloration (cyanosis) that had lasted for a month, as well as a cough and breathing difficulties that had recently started.
A battery of clinical evaluations were performed, and she was found to have hypertrophic cardiomyopathy — one of the typical symptoms of classic IOPD, in which the walls of the heart become abnormally thick.
The baby was treated symptomatically for a week. This included ventilation, active anti-infection treatment, and therapies aimed at improving her heart and kidney function. However, these treatments failed to ease her symptoms, and the young girl was then transferred to another hospital at her parents’ request. She passed away at the other hospital a few days later.
Following her death, and with her family’s consent, the investigators from the initial treatment center measured the activity of GAA in blood samples that had been previously taken from the patient. They found that GAA activity was abnormally low (0.18 nM/punch/hour; normal range 8-97.7 nM/punch/hour).
Gene sequencing revealed the baby had mutations in both copies of the GAA gene, one inherited from each parent, who were later found to be carriers. The specific mutations were c.1822C>T and c.2297A>C, named for the specific nucleotide changes in the DNA sequence of the GAA gene. Neucleotides are the building blocks that make up DNA gene sequences.
Although both mutations had previously been implicated in PD, this was the first reported case of both occurring in the same patient, and leading to symptoms of classical IOPD.
Broadly, this case report highlights the need for better early diagnosis of Pompe, the researchers said, as early identification could lead to treatments being given while they are effective.
“Although PD is rare, and universal screening has not been established, we suggest that clinicians should consider the possibility of PD in the presence of hypertrophic cardiomyopathy,” the investigators said.
“At the same time, we suggest that we should further expand the newborn screening of PD and establish a more sensitive, complete, and inexpensive screening system, in order to improve the prognosis of infants with IOPD by early diagnosis,” they added.
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