A Case of ALMS1 Compound Heterozygous Variant Causing Alstrom Syndrome

doi:10.12280/gjszjk.20250132

Abstract

Abstract:

Alstrom syndrome is an autosomal recessive disorder with multisystem involvement caused by the mutations in ALMS1 gene. The pathogenesis of the disease is not fully understood, the effective treatment is also lacking, and the prognosis is poor. The young age of onset, wide range of clinical symptoms and varying severity of the disease make it difficult to diagnose and treat. We report a female case of Alstrom syndrome diagnosed by whole exome sequencing (WES). The patient presented with congestive heart failure, congenital cardiomyopathy, atrial septal defect, growth retardation and recurrent pneumonia. She was given symptomatic treatments including infection control, cardiotonic, diuretic, and calcium supplementation, but the final prognosis was poor. The ALMS1 compound heterozygous variant c.11647_c.11648delAT (p.M3883fs*9)/ c.2888_c.2897del GTGTTTTCTA (p.S963fs*15) was found to be a rare variant. The discovery of this compound heterozygous variant provided a new reference for the genetic study of Alstrom syndrome.

Key words: Alstrom syndrome, Whole exome sequencing, Heart failure, Pneumonia, ALMS1

CHEN Hui-fang, ZUO Wen-tao, ZHAO Ling-zhi, CHEN Jin-fan, HUI Ling, ZHANG Chuan. A Case of ALMS1 Compound Heterozygous Variant Causing Alstrom Syndrome[J]. Journal of International Reproductive Health/Family Planning, 2025, 44(6): 459-463.

Figures/Tables 3

References 16

[1]	Marshall JD, Maffei P, Beck S, et al. Clinical utility gene card for: Alström Syndrome - update 2013[J]. Eur J Hum Genet,2013 Nov; 21(11). doi: 10.1038/ejhg.2013.61.
[2]	Wang C, Luo X, Wang Y, et al. Novel Mutations of the ALMS1 Gene in Patients with Alström Syndrome[J]. Intern Med, 2021, 60(23):3721-3728. doi: 10.2169/internalmedicine.6467-20.
[3]	Tahani N, Maffei P, Dollfus H, et al. Consensus clinical management guidelines for Alström syndrome[J]. Orphanet J Rare Dis, 2020, 15(1):253. doi: 10.1186/s13023-020-01468-8. pmid: 32958032
[4]	王云芳, 万小艳, 牛瑞兰, 等. Alstrom综合征两例报道[J]. 中国糖尿病杂志, 2023, 31(2):139-144. doi: 10.3969/j.issn.1006-6187.2023.02.012.
[5]	Choudhury AR, Munonye I, Sanu KP, et al. A review of Alström syndrome: a rare monogenic ciliopathy[J]. Intractable Rare Dis Res, 2021, 10(4):257-262. doi: 10.5582/irdr.2021.01113.
[6]	Waldman M, Han JC, Reyes-Capo DP, et al. Alström syndrome: Renal findings in correlation with obesity, insulin resistance, dyslipidemia and cardiomyopathy in 38 patients prospectively evaluated at the NIH clinical center[J]. Mol Genet Metab, 2018, 125(1/2):181-191. doi: 10.1016/j.ymgme.2018.07.010.
[7]	Sanyoura M, Woudstra C, Halaby G, et al. A novel ALMS1 splice mutation in a non-obese juvenile-onset insulin-dependent syndromic diabetic patient[J]. Eur J Hum Genet, 2014, 22(1):140-143. doi: 10.1038/ejhg.2013.87. pmid: 23652376
[8]	Nerakh G, Ranganath P. Alström Syndrome Presenting as Isolated Dilated Cardiomyopathy[J]. Indian J Pediatr, 2019, 86(3):296-298. doi: 10.1007/s12098-018-2807-9. pmid: 30484169
[9]	Shenje LT, Andersen P, Halushka MK, et al. Mutations in Alström protein impair terminal differentiation of cardiomyocytes[J]. Nat Commun, 2014,5:3416. doi: 10.1038/ncomms4416.
[10]	Jiang P, Xiao L, Guo Y, et al. Novel mutations of the Alström syndrome 1 gene in an infant with dilated cardiomyopathy: A case report[J]. World J Clin Cases, 2022, 10(7):2330-2335. doi: 10.12998/wjcc.v10.i7.2330. pmid: 35321175
[11]	Marshall JD, Bronson RT, Collin GB, et al. New Alström syndrome phenotypes based on the evaluation of 182 cases[J]. Arch Intern Med, 2005, 165(6):675-683. doi: 10.1001/archinte.165.6.675. pmid: 15795345
[12]	Hearn T. ALMS1 and Alström syndrome: a recessive form of metabolic, neurosensory and cardiac deficits[J]. J Mol Med(Berl), 2019, 97(1):1-17. doi: 10.1007/s00109-018-1714-x.
[13]	Burgy O, Königshoff M. The WNT signaling pathways in wound healing and fibrosis[J]. Matrix Biol, 2018, 68/69:67-80. doi: 10.1016/j.matbio.2018.03.017.
[14]	牛兆霞, 杨美荣, 陈桂芝. Alstrom综合征的诊治进展[J]. 青岛医药卫生, 2007, 39(6):442-444. doi: 10.3969/j.issn.1006-5571.2007.06.026.
[15]	张倩文. Alstrom综合征的发病机制及诊治进展[J]. 国际儿科学杂志, 2020, 47(1):59-62. doi: 10.3760/cma.j.issn.1673-4408.2020.01.015.
[16]	Han JC, Reyes-Capo DP, Liu CY, et al. Comprehensive Endocrine-Metabolic Evaluation of Patients With Alström Syndrome Compared With BMI-Matched Controls[J]. J Clin Endocrinol Metab, 2018, 103(7):2707-2719. doi: 10.1210/jc.2018-00496. pmid: 29718281