Despite disease symptoms, long delays seen for a Fabry diagnosis in children
Family screening key to earlier detection in kids, per new study in China
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Children with Fabry disease typically experience long delays before receiving a diagnosis, despite symptoms affecting multiple organs that often emerge in early childhood, a nationwide study in China has found.
Overall, a median diagnostic delay of at least four years was seen among the more than 60 children in the Asian nation who were involved in the new study.
The findings also showed that boys tended to develop Fabry symptoms earlier and experience more severe disease, with nerve-related pain emerging as the most common early symptom. Both boys and girls also experienced absent or reduced sweating, heart rhythm abnormalities, and eye issues, the data showed. Some boys also had signs of kidney involvement.
Treatment initiation was also modestly delayed, highlighting the ongoing need to improve early diagnosis and access to therapy, according to the researchers.
The team noted that family screening helped identify many cases — particularly among girls — underscoring its value for earlier detection.
This study “highlights substantial diagnostic delays and underscores the importance of [multidisciplinary team] collaboration, family screening, and early recognition to improve outcomes in affected children,” the researchers wrote.
The study, “Multidisciplinary approach to the assessment and management of children with Fabry disease: Insights from the Chinese Children Genetic Kidney Disease Database,” was published in the journal Intractable & Rare Diseases Research.
A genetic disease, Fabry is caused by mutations in the GLA gene that lead to dysfunction of the enzyme alpha-galactosidase A (alpha-Gal A). As a result, fatty molecules such as globotriaosylceramide (Gb3) and lyso-Gb3 accumulate to toxic levels in cells and tissues. Over time, this buildup can damage multiple organs, including the kidneys, heart, and nervous system.
Fabry disease symptoms can be subtle, making diagnosis difficult
Although symptoms often begin in childhood, signs of the Fabry can vary widely and may be subtle at first, making the disease difficult to recognize. As a result, patients may experience long delays between the onset of first symptoms and diagnosis.
Early diagnosis, however, offers a critical opportunity to begin treatment before irreversible organ damage occurs, the researchers noted.
To help improve early detection, the Children’s Hospital of Fudan University established China’s first multidisciplinary team (MDT) dedicated to pediatric Fabry diagnosis and care in April 2020. The program introduced a referral system combining symptom-based risk assessment, family screening, and dried blood spot testing to measure alpha-Gal A activity, lyso-Gb3 levels, and GLA gene mutations. The initiative later expanded nationwide, and by early 2022, the MDT model had been implemented in 21 medical centers.
“A clearer understanding of pediatric [Fabry disease characteristics] in China is essential for guiding both diagnosis and long-term management,” the researchers wrote.
To learn more, the team analyzed the clinical characteristics and treatment status of 64 children diagnosed with Fabry before March 2025 through the MDT network. The analysis drew on data from the Chinese Children’s Genetic Kidney Disease Database, a national registry that collects clinical information on children with inherited kidney disorders.
The group comprised 46 boys and 18 girls. The median age at diagnosis was 11.4 years in boys and 9.4 years in girls. Symptoms typically began earlier — at 6.4 years in boys and 7 years in girls — leading to median diagnostic delays of 4.4 years for boys and 4.0 years for girls, according to the researchers.
Nerve-related pain was the most common early symptom, reported as the first sign of disease in 52% of boys and 28% of girls, typically beginning at about age 8. The pain typically appeared as acroparesthesia, a burning, tingling, or numb sensation affecting the hands and feet.
Over 70% of girls with Fabry diagnosed through family testing
Family screening played a major role in detecting cases, the researchers noted. About 72% of girls and 35% of boys were diagnosed through family testing. In three boys (7%), GLA mutations were discovered incidentally during genetic testing for unrelated conditions.
Missense mutations — genetic changes that alter a single building block in the alpha-Gal A enzyme — were the most common mutation type, detected in 65% of boys and 67% of girls. Boys showed markedly reduced alpha-Gal A enzyme activity, while girls often had enzyme levels within the normal range. Nevertheless, elevated lyso-Gb3 levels were detected in most patients of both sexes.
As the disease progressed, nerve-related pain became common, affecting 91% of boys and 39% of girls at follow-up. Again, the pain most often presented as acroparesthesia and was most often described as burning sensations in boys (53%) and tingling in girls (57%).
Absent or reduced sweating, known as anhidrosis or hypohidrosis, occurred in 59% of boys and 11% of girls. An eye abnormality called cornea verticillata — a swirl-like pattern on the cornea that usually does not affect vision — was observed in 49% of boys and 54% of girls.
Signs of kidney involvement were detected in 15% of boys with available data. Heart rhythm abnormalities, or arrhythmias, occurred in 28% of boys and 44% of girls, while left ventricular hypertrophy — a thickening of the heart muscle — was reported in 8% of boys.
Respiratory problems affected nearly one-quarter of the boys, while hearing loss was reported in 11%, and low bone mineral density — indicating weaker bones — was detected in four of the seven boys tested.
Findings from this Chinese [group] underscore the importance of [multidisciplinary team]-driven strategies, family screening, and early therapeutic intervention to improve long-term outcomes in Chinese children with [Fabry].
Overall, 37 children received enzyme replacement therapy (ERT), most commonly Fabrazyme (agalsidase beta), the data showed. Treatment began at a median age of 12.9 years in boys and 11.7 years in girls, corresponding to a median of 7.3 years after symptom onset in boys and four years in girls. The therapy was generally well-tolerated, the researchers noted.
Severe complications were rare. One boy (2%) required a kidney transplant, and no deaths, heart-related events, or strokes were reported.
According to the researchers, altogether, the “findings from this Chinese [group] underscore the importance of MDT-driven strategies, family screening, and early therapeutic intervention to improve long-term outcomes in Chinese children with [Fabry].”
