Cough is only symptom in man later diagnosed with Fabry disease
Pulmonary involvement is rare and can be overlooked
A chronic cough was the only initial symptom in a 46-year-old man who was eventually diagnosed with Fabry disease, a case study indicates.
“This case highlights that chronic cough may be an important clue for pulmonary involvement in [Fabry disease] and should prompt further evaluation in patients with other features suggestive of [Fabry],” the researchers wrote in the study, “Chronic Cough as the First Clinical Sign of Fabry Disease: A Case Report,” which was published in Cureus.
The alpha-galactosidase A (alpha-Gal A) enzyme breaks down certain fatty molecules, mainly globotriaosylceramide (Gb3), and others, inside cells’ recycling centers, called lysosomes. But in Fabry disease, mutations in the GLA gene, which encodes alpha-Gal A, result in an enzyme deficiency and Gb3 building up to toxic levels, damaging various tissues.
Common symptoms include pain in the hands and feet, gastrointestinal issues, skin rash, eye changes, and more severe complications such as heart disease and kidney failure. Lung involvement can be overlooked due to its nonspecific signs and symptoms, including cough and shortness of breath.
Longtime cough leads to Fabry diagnosis
Here, researchers in Poland describe a 46-year-old man who was seen with a chronic cough of several years that led to his being diagnosed with Fabry disease.
“To the best of our knowledge, this is the first case report of a patient with [Fabry disease] who presented with chronic cough as the first and only reported clinical symptom,” the researchers wrote.
The man didn’t smoke or have asthma, gastroesophageal reflux disease, allergies, or lung infections. He also had no chest pain, wheezing, or shortness of breath, and reported no abnormal weight loss, fever, or night sweats. He was not taking medications.
Blood tests revealed high levels of creatinine, a sign of kidney impairment, however. The man was admitted to the hospital for further assessment because a maternal cousin had been diagnosed with Fabry at age 17, and had kidney failure and a kidney transplant.
A physical exam was normal, except for high blood pressure. An ultrasound of his abdomen found smaller than normal kidneys, a lack of differentiation between the outer and inner kidney layers, and a lesion in the left kidney. No abnormalities were seen in other abdominal organs.
A blood test of alpha-Gal A showed no enzyme activity and genetic testing revealed a mutation in the GLA gene, confirming Fabry disease. The patient then reported recurrent burning sensations in his hands that only occurred with a fever.
An electrocardiogram, which measures the heart’s electrical activity, found irregularities, including a slower than normal heart rate. An echocardiogram found evidence of cardiomyopathy, a disease of the heart muscle. A neurological exam showed no significant abnormalities.
A chest X-ray was normal, with no signs of infection or congestion, but lung function tests revealed evidence of an airway blockage. CT scans showed signs of pulmonary fibrosis (scarring) and lung tissue damage. Inflammation of the airways was also noted. So-called zebra bodies were detected in lung tissues with a microscopic analysis, indicating Gb3 buildup.
He started enzyme replacement therapy (ERT), specifically agalsidase alfa, which provides a lab-made source of alpha-Gal A. The man was also given dialysis due to chronic kidney disease, but eventually had a kidney transplant, which was fully functional a year later. His cough remained despite treatment and he continued to report it as his most bothersome symptom.
The man’s daughter was also found via a family screening to have Fabry disease and received ERT after presenting with burning sensations in her feet. The man’s sister also had Fabry, but no details were available.
“Our case illustrates that chronic cough may be a sign of pulmonary involvement in [Fabry disease],” the researchers wrote. “Its presence paired with unexplained renal impairment or a positive family history should prompt further diagnostic workup for [Fabry disease].”
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