Late onset dilated cardiomyopathy in a unique familial syndrome of hypogonadism and metabolic abnormalities

Warren, Sanford E.; Schnitt, Stuart J.; Bauman, A.; Gianelly, Ralph E.; Landsberg, Lewis; Baim, Donald S.

doi:10.1016/0002-8703(87)90561-8

Cited by 30 publications

(26 citation statements)

References 3 publications

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“…ALMS DCM, which is the most common cause of morbidity and mortality in ALMS (3, 28), is usually related to myocardial fibrosis, given the multiorgan fibrotic involvement that characterizes this syndrome; however, pathologic evidence of cardiac fibrosis has been provided only in a limited number of cases (3, 5,6). …”

Section: Discussionmentioning

confidence: 99%

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Alström Syndrome: Cardiac Magnetic Resonance findings

Corbetti

Razzolini

Bettini

et al. 2013

International Journal of Cardiology

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Background Alström Syndrome (ALMS) is an extremely rare multiorgan disease caused by mutations in ALMS1. Dilated Cardiomyopathy (DCM) is a common finding but only one series has been investigated by Cardiac Magnetic Resonance (CMR). Methods Eight genetically proven ALMS patients (ages 11–41) underwent CMR performed by standard cine steady state, T1, T2 and Late Gadolinium Enhancement (LGE) sequences. Ejection fraction (EF), Diastolic Volume (EDV) and Systolic Volume normalized for body surface area (ESV), and Mass indices were determined, as well as EDV/Mass ratio, an index expressing the adequacy of cardiac mass to heart volume. Regional fibrosis was assessed by LGE; diffuse fibrosis was measured by a TI scout sequence acquired at 5, 10 and 15 min after gadolinium by comparing inversion time values (TI) at null time in ALMS and control group. Results In one patient severe DCM was present with diffuse LGE. There were seven cases without clinical DCM. In these patients, EF was at lower normal limits or slightly reduced and ESV index increased; six patients had decreased Mass index and EDV/Mass ratio. Mild regional non ischemic fibrosis was detected by LGE in three cases; diffuse fibrosis was observed in all cases, as demonstrated by shorter TI values in ALMS in comparison with controls (5 min:152±12 vs 186±16, p 0,0002; 10 min: 175±8 vs 204±18, p 0,0012; 15 min: 193± 9 vs 224±16, p 0,0002). Conclusions Cardiac involvement in ALMS is characterized by progressive DCM, associated with systolic dysfunction, myocardial fibrosis and reduced myocardial mass.

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Section: Discussionmentioning

confidence: 99%

“…Severe to moderate interstitial fibrosis was found in the hearts of seven ALMS cases with medical history of DCM (3,5,6), while mild interstitial myocardial fibrosis was present in one patient without a prior history of DCM (3). …”

Section: Introductionmentioning

confidence: 98%

Alström Syndrome: Cardiac Magnetic Resonance findings

Corbetti

Razzolini

Bettini

et al. 2013

International Journal of Cardiology

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“…Low-normal levels of testosterone and elevated gonadotropins are suggestive of a primary gonadal failure [53,54]. Males have small external genitalia and testicular atrophy with obliterating fibrosis of seminiferous tubules [4]; however, sporadic spermatozoa can be found in the seminal fluid.…”

Section: Alström Syndrome Clinical Overviewmentioning

confidence: 99%

Alstrom Syndrome: Genetics and Clinical Overview

Marshall

Maffei²,

Collin³

et al. 2011

231

298

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Alström syndrome is a rare autosomal recessive genetic disorder characterized by cone-rod dystrophy, hearing loss, childhood truncal obesity, insulin resistance and hyperinsulinemia, type 2 diabetes, hypertriglyceridemia, short stature in adulthood, cardiomyopathy, and progressive pulmonary, hepatic, and renal dysfunction. Symptoms first appear in infancy and progressive development of multi-organ pathology leads to a reduced life expectancy. Variability in age of onset and severity of clinical symptoms, even within families, is likely due to genetic background.Alström syndrome is caused by mutations in ALMS1, a large gene comprised of 23 exons and coding for a protein of 4,169 amino acids. In general, ALMS1 gene defects include insertions, deletions, and nonsense mutations leading to protein truncations and found primarily in exons 8, 10 and 16. Multiple alternate splice forms exist. ALMS1 protein is found in centrosomes, basal bodies, and cytosol of all tissues affected by the disease. The identification of ALMS1 as a ciliary protein explains the range of observed phenotypes and their similarity to those of other ciliopathies such as Bardet-Biedl syndrome.Studies involving murine and cellular models of Alström syndrome have provided insight into the pathogenic mechanisms underlying obesity and type 2 diabetes, and other clinical problems. Ultimately, research into the pathogenesis of Alström syndrome should lead to better management and treatments for individuals, and have potentially important ramifications for other rare ciliopathies, as well as more common causes of obesity and diabetes, and other conditions common in the general population.

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“…All patients have normal intellectual function (2). Late-appearing manifestations are hepatic dysfunction similar to chronic active hepatitis, dilated cardiomyopathy, and renal dysfunction (2,3,7,10,11). An overview of all features of Alstrom syndrome is presented in Table 1.…”

Section: Conclusion-mentioning

confidence: 99%