Abstract
Alström syndrome (ALMS) is an ultra-rare monogenic disease characterized by insulin resistance, multi-organ fibrosis, obesity, type 2 diabetes mellitus (T2DM), and hypertriglyceridemia with high and early incidence of non-alcoholic fatty liver disease (NAFLD). We evaluated liver fibrosis quantifying liver stiffness (LS) by shear wave elastography (SWE) and steatosis using ultrasound sonographic (US) liver/kidney ratios (L/K) in 18 patients with ALMS and 25 controls, and analyzed the contribution of metabolic and genetic alterations in NAFLD progression. We also genetically characterized patients. LS and L/K values were significantly higher in patients compared with in controls (p < 0.001 versus p = 0.013). In patients, LS correlated with the Fibrosis-4 Index and age, while L/K was associated with triglyceride levels. LS showed an increasing trend in patients with metabolic comorbidities and displayed a significant correlation with waist circumference, the homeostasis model assessment, and glycated hemoglobin A1c. SWE and US represent promising tools to accurately evaluate early liver fibrosis and steatosis in adults and children with ALMS during follow-up. We described a new pathogenic variant of exon 8 in ALMS1. Patients with ALMS displayed enhanced steatosis, an early increased age-dependent LS that is associated with obesity and T2DM but also linked to genetic alterations, suggesting that ALMS1 could be involved in liver fibrogenesis.
Highlights
We described a new pathogenic variant of ALMS1 in exon 8: c.2611_2614delTTCT p.(Phe871Ilefs*10), a deletion of four nucleotides causing a frameshift and predicting a truncated protein of only 871 amino acids compared with the wild type spanning 4169 aa (Table 2)
The prevalence of overt type 2 diabetes mellitus (T2DM) in patients with Alström syndrome (ALMS) was 44% (8/18), the prevalence of obesity was 28% (5/18), hypertension was present in 33% (6/18), and the prevalence of metabolic syndrome was 56% (10/18)
We found of association between steatosis, and determined transaminases
Summary
Alström syndrome (ALMS; OMIM #203800) is an ultra-rare, autosomal recessive monogenic disease characterized by a wide spectrum of clinical manifestations involving insulin resistance (IR), multi-organ fibrosis, obesity, type 2 diabetes mellitus (T2DM), hypertriglyceridemia, and hepatic dysfunction [1,2,3]. Liver involvement in ALMS was firstly described with pathological findings of chronic active hepatitis in a child [16]. Acute liver failure, hepatocellular carcinoma (HCC), and esophageal varices bleeding were observed in young patients [17,18,19,20]. An evaluation from all over the world reporting hepatic and gastrointestinal findings in 97 patients with
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