SBMA Patients are More Likely to be Affected by Metabolic Disorders, Heart and Liver Disease, Study Says

Joana Carvalho, PhD avatar

by Joana Carvalho, PhD |

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metabolic disorders, SBMA

Patients with spinal-bulbar muscular atrophy (SBMA) are more likely to be affected by metabolic disorders, including insulin resistance and fatty liver disease, which can lead to heart disease and serious liver damage, a study says.

The study, “Prevalence of metabolic syndrome and non-alcoholic fatty liver disease in a cohort of Italian patients with spinal-bulbar muscular atrophy,” was published in Acta Myologica.

SBMA, also known as Kennedy’s disease, is a type of spinal muscular atrophy (SMA) that starts in adulthood and is characterized by widespread muscle weakness and wasting in the arms, legs, head, and neck (bulbar involvement).

The disorder is caused by mutations in the androgen receptor (AR) gene — located on the X chromosome — that lead to an abnormal expansion of a CAG nucleotide (the building blocks of DNA) repeat in the AR gene sequence and to the production of a much larger dysfunctional protein.

Besides neurologic symptoms, SBMA patients also tend to be affected by medical conditions associated with metabolic syndrome (a series of conditions that increase patients’ risk of developing heart disease, stroke or type 2 diabetes), such as insulin resistance, obesity, and glucose intolerance.

In the study, researchers at the University of Padua, in Italy, assessed the incidence of metabolic syndrome, insulin resistance, and non-alcoholic fatty liver disease (NAFLD) in a group of SBMA patients.

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The study involved a total of 47 Italian patients with a confirmed diagnosis of SBMA who underwent a battery of biochemical tests to assess metabolic functions. A subset of 24 patients were examined by abdominal sonography (an imaging technique that allows physicians to visualize structures in the patients’ abdominal cavity).

Results showed that 49% of the patients had abnormally high levels of fasting glucose (commonly used to diagnose diabetes), and 66% showed signs of insulin resistance.

In addition, 51% of the patients had high levels of total cholesterol, 38% had high LDL-cholesterol (“bad” cholesterol), and 38% had high triglycerides. Conversely, 77% had low levels of HDL-cholesterol (“good” cholesterol). More than half of the patients (55%) had three or more medical conditions associated with metabolic syndrome.

Researchers also found a positive relationship between insulin resistance and the length of CAG repeats in the AR gene sequence.

Biochemical tests showed high levels of two liver enzymes that, when elevated, may indicate liver inflammation or damage: aspartate transaminase (AST) levels were abnormally high in 62% of patients, and alanine transaminase (ALT) levels were high in 38% of patients.

Abdominal sonography revealed that 92% of the patients had liver steatosis (fatty liver disease) at different levels of severity, and one patient had liver cirrhosis (scarring of the liver).

“These alterations can be explained mainly by the reduction of testosterone activity because of (CAG repeats’) expansion in AR gene and must be considered as a main characteristic of Kennedy’s disease,” the researchers wrote.

“Metabolic alterations in SBMA are a suggestive model of androgen deprivation in male and require a multidisciplinary approach to disease. However, considering the conflicting data on the role of androgen stimulation in the metabolic involvement, further studies are needed to understand the pathogenesis of NAFLD and (insulin resistance) in SBMA patients and the possible detrimental consequences of anti-androgen approaches to disease,” they concluded.