A Case Report of two siblings with Alstrom syndrome without hearing loss associated with two new ALMS1 variants

Shurygina, M. F.; Parker, Maria A.; Schlechter, Catie; Chen, Rui; Li, Yumei; Weleber, Richard G.; Yang, Paul; Pennesi, Mark E.

doi:10.21203/rs.2.9239/v4

Cited by 1 publication

(1 citation statement)

References 21 publications

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“…Almost all of the mutations are frameshift or nonsense mutations. The function of the ALMS1 gene is not well understood, but it has been implicated in cell cycle regulation and intracellular transport, in addition to ciliary disease (5). The clinical findings frequently observed in patients with ALMS are sophisticated and vary considerably.…”

Section: Introductionmentioning

confidence: 99%

Whole-exome sequencing establishes a diagnosis of Alstrom syndrome: a case report

Liu¹,

Chen²

2022

Transl Pediatr

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Background: Alstrom syndrome (ALMS) is a rare genetic disorder. ALMS is characterized by progressive bilateral sensorineural hearing impairment, cone-rod dystrophy, infantile-onset cardiomyopathy, hypertriglyceridemia, accelerated non-alcoholic fatty liver disease, renal dysfunction and insulin-resistant diabetes mellitus (DM). DM typically develop in childhood or adolescence. Dilated cardiomyopathy may arise in infancy. Clinical symptoms appear with great variability and severity. Several cases have been reported worldwide; however, diagnosis remains challenging.Case Description: We report an 8-year-and-11-month-old female diagnosed with ALMS who had a long history of obesity and amblyopia from infancy. We found high levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in this patient. She showed no hearing disfunction. Recently, she presented with sudden-onset insulin-resistant DM. Genetic analysis revealed the heterozygous mutations c.8366delT, p.L2789* and c.6829C>T, p.R2277*. c.8366delT, which results in premature protein termination, has not been reported previously in ALMS1. Although the patient's two sisters died of acute heart failure following infection at 4 and 14 months respectively, she showed no signs of cardiomyopathy until now. Conclusions:This case provides an unusual cause of genetic syndrome associated with diabetes. A detailed medical history, physical examination and appropriate gene analysis are critical for diagnosis. Our case identifies a novel ALMS1 mutation and reaffirms the great clinical variation of this disease even within families.

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Section: Introductionmentioning

confidence: 99%