A family report of Fabry disease presenting with bilateral foot pain as the initial symptom, identified by GLA gene detection showing c.718_719 del (p.Lys240Glufs*9) heterozygous deletion, with enzyme replacement therapy improving pain symptoms.
A 16-year-old female patient presented with recurrent bilateral foot pain for 7 years as the initial symptom of Fabry disease, with onset at age 9.
The patient's father had a similar clinical history, with symptom onset at age 10 and confirmed diagnosis of uremia at age 37, and is currently on long-term hemodialysis.
α-Galactosidase A (α-Gal A) enzyme activity testing showed normal enzyme activity in the female patient but significantly reduced activity in the father.
GLA gene testing identified a c.718_719 del (p.Lys240Glufs*9) mutation, with the patient carrying a heterozygous deletion and the father carrying a hemizygous deletion.
Enzyme replacement therapy initiated in the patient resulted in improvement of pain symptoms.
Analysis of this family's clinical features was conducted to improve clinicians' ability to identify Fabry disease presenting with neuropathic pain as the initial symptom.
This research describes a Chinese family with Fabry disease, a rare inherited condition caused by a deficiency of an enzyme called alpha-galactosidase A. The case centers on a 16-year-old girl who had been experiencing recurrent burning and stabbing pain in both feet since age 9. Her father had the same symptoms starting at age 10, but was not diagnosed until age 37 when he had already developed kidney failure and required dialysis. Genetic testing confirmed both family members carried a mutation in the GLA gene (c.718_719 del), which is responsible for producing the deficient enzyme. This research suggests that bilateral neuropathic foot pain in children and adolescents can be an early warning sign of Fabry disease, and that early recognition is critical. The girl's enzyme activity appeared normal on standard testing (which can happen in females with this condition due to its X-linked inheritance), but genetic testing confirmed the diagnosis. After starting enzyme replacement therapy — a treatment that supplements the missing enzyme — her pain symptoms improved, highlighting the benefit of early intervention before organ damage occurs. The key practical message from this case is that doctors should consider Fabry disease when evaluating young patients, particularly children, who present with unexplained neuropathic (nerve-related) pain in the feet. Family history is an important clue: the father's delayed diagnosis led to irreversible kidney damage, whereas the daughter's earlier identification may allow her to avoid such severe complications. This report aims to raise awareness among clinicians so that similar patients are recognized and treated sooner.
Kong L, Li Y, Guo R, Li C. (2026). [A family report of Fabry disease with bilateral foot pain as the initial symptom].. Zhonghua nei ke za zhi. https://doi.org/10.3760/cma.j.cn112138-20251230-00803