Case of 59-Year-Old Highlights Variability in Fabry Disease Presentation

A new case report highlights a patient who presented with seizure-like symptoms but was later diagnosed with the rare lysosomal storage disorder.

Fabry disease (FD) is a rare disease, but is also highly variable in its presentation. In a new case report, clinicians offer insights into the disease’s variability by describing a 59-year-old man who was diagnosed with non-classical Fabry after presenting with convulsive crises.

Writing in the journal Cureus, corresponding author Cláudia Ferreira Tátá, of the Hospital do Espírito Santo de Évora in Portugal, and colleagues explained that FD is caused by mutations of the Galactosidase Alpha (GLA) gene, leading to an absence of decrease of the lysosomal enzyme α-Galactosidase A (α-Gal A). This eventually leads to the accumulation of globotriaosylceramide (Gb3) and related glycosphingolipids in lysosomes, which triggers organ dysfunction and damage, they wrote.

The patient in question had a long history of health problems. He had suffered from high blood pressure for a decade, and was also experiencing psychomotor slowing, episodes of dysphagia, irritability, decreased hearing, vertigo and paraesthesia, and lower-limb pain. He had a family history of depression and dementia.

He arrived at the emergency department after an episode the investigators said was consistent with a tonic-clonic seizure, as well as sphincter incontinence. While at the emergency department, he experienced a second convulsive seizure, though it was controlled with diazepam and he was later transferred to the intensive care unit. The patient appeared clinically stable, though additional tests were ordered. Of concern, the patient had apparent neurological deficits and his hypertension was difficult to control, authors explained.

Investigators eventually undertook a test of enzymatic activity, which subsequently revealed enzyme deficiency of α-Gal A, leading investigators to a diagnosis of non-classical FD.

The authors noted that the patient in the study had white matter lesions (WML) visible on MRI, something that is generally uncommon in patients under the age of 50, though it is common in those over age 65. Cerebral WMLs are common, however, in patients with FD.

This case of Fabry is unique, the authors said, due to the patient’s age and the presentation with epilepsy.

“Although he is not a patient under 50 years old, due to cognitive dysfunction, neuropathic pain, subjective hearing loss that raises the hypothesis of cochleovestibular dysfunction and psychiatric symptoms, together with lesions compatible with small vessel microangiopathy, a common expression of cerebral vasculopathy in FD, it was decided to continue the study of less frequent causes of WML, despite [the fact] these could be justified by the patient risk factors (hypertension, smoking and dyslipidaemia),” they wrote.

In addition to α-Gal A deficiency, the authors also identified hemizygosity for the p.A143T mutation, though they said that mutation’s association with Fabry remains controversial.

“Regarding the case presented, which carries the p.A143T mutation (thus considered a variant of unknown significance), given that there is clinical and biochemical evidence of the disease (reduced leukocyte enzymatic activity), FD is considered as the final diagnosis,” they said.

The authors said the patient was referred to other specialists to identify and treat other manifestations of the disease, and the patient and his family were also offered genetic counseling.

They said this case represents a reminder of the heterogeneity of the disease, and of the importance of being attuned to its subtle manifestations.

“Thus, being alert to FD's manifestations, even if subtle, diagnosing FD and starting treatment when indicated is essential to change the natural history of the disease and the quality of life of a patient and their family,” they concluded.


Ferreira Tátá C, Massas M, Pinto F, Caçador N, and Silva AL. Fabry disease: a atypical presentation. Cureus. Published online October 12, 2021. doi:10.7759/cureus.18708