2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-The Rare in the Common: Unsuspected Fabry Disease

Pdf Summary

Fabry disease (FD) is a rare genetic lysosomal storage disease caused by a deficiency in the enzyme alpha-galactosidase A. It is an X-linked disorder with a frequency of 1 in 40,000 males. FD often goes undiagnosed, but it can present with various clinical manifestations. In males, the classical form of FD is characterized by symptoms such as periodic acroparesthesias, angiokeratomas, corneal verticillata, gastrointestinal issues, and progressive organ involvement leading to cardiovascular, cerebrovascular, and renal complications. Heterozygous females may have milder symptoms and a later onset, but they can still develop cardiovascular, cerebrovascular, and renal problems. <br /><br />A five-generation family with 20 affected members of FD was studied. Diabetes mellitus, obesity, rheumatoid arthritis, and Grave's disease were found to be common among the family members. The family tree helped identify affected individuals and facilitated their evaluation and medical follow-up. The study emphasizes the importance of early diagnosis for adequate treatment of FD and recommends actively searching for other affected family members when an index case is detected.<br /><br />The study also highlights that FD is often underdiagnosed or misdiagnosed, and including FD testing in neonatal blood screening has significantly increased the diagnosis rate. Late-onset genetic variants of FD detected through neonatal screening have presented new challenges in determining the best time for diagnosis and treatment. Atypical symptoms of FD, such as chronic intestinal pseudo-obstruction and isolated lymphedema, have also been reported. <br /><br />The successful approach of this family study was attributed to the collaboration of multidisciplinary teams and the identification of common diseases that coexist with FD, suggesting a possible relationship between immunological diseases and FD. The study concludes by calling for continued research and awareness about FD to improve diagnosis and treatment outcomes.

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Co-Author - Silvina Noemi N. Contreras-Capetillo, MD, MMSc; Co-Author - Ricardo E. Pech-George, MD, Psychiatrist; Co-Author - Ruy D. Arjona-Villacaña, MD, Endocrinologist; Co-Author - Jorge A. Rangel-Méndez, PHD, PhD in health sciences; Co-Author - Doris C. Pinto-Escalante, MD, Medical Geneticist; Co-Author - Alejandro Gaviño-Vergara, ME, Medical Geneticist; Co-Author - Héctor G. Cámara-Castillo, MD, Medical ophthalmology; Presenting Author - Silvina N. Contreras-Capetillo, MD, Medical Geneticist;

Meta Tag

Clinical History

Diabetes

Enzyme Replacement Therapy

Genetic Testing

Lysosomal Diseases

Metabolic Disorder

Phenotype

Co-Author Silvina Noemi N. Contreras-Capetillo, MD, MMSc

Co-Author Ricardo E. Pech-George, MD, Psychiatrist

Co-Author Ruy D. Arjona-Villacaña, MD, Endocrinologist

Co-Author Jorge A. Rangel-Méndez, PHD, PhD in health sciences

Co-Author Doris C. Pinto-Escalante, MD, Medical Geneticist

Co-Author Alejandro Gaviño-Vergara, ME, Medical Geneticist

Co-Author Héctor G. Cámara-Castillo, MD, Medical ophthalmology

Presenting Author Silvina N. Contreras-Capetillo, MD, Medical Geneticist

Keywords

Fabry disease

lysosomal storage disease

alpha-galactosidase A deficiency

X-linked disorder

cardiovascular complications

cerebrovascular complications

renal complications

heterozygous females

neonatal blood screening

chronic intestinal pseudo-obstruction