Progressive psychomotor regression for 2.5 years in a boy aged 5 years

TIAN Mao-Qiang; CHEN Xiao-Xi; LI Lei; LANG Chang-Hui; LI Juan; CHEN Jing; YU Xiao-Hua; SHU Xiao-Mei

doi:10.7499/j.issn.1008-8830.2201048

PDF(1973 KB)

Chinese Journal of Contemporary Pediatrics ›› 2022, Vol. 24 ›› Issue (6) : 699-704. DOI: 10.7499/j.issn.1008-8830.2201048

CASE ANALYSIS

Progressive psychomotor regression for 2.5 years in a boy aged 5 years

TIAN Mao-Qiang, CHEN Xiao-Xi, LI Lei, LANG Chang-Hui, LI Juan, CHEN Jing, YU Xiao-Hua, SHU Xiao-Mei

Author information +

History +

Abstract

A boy, aged 5 years, attended the hospital due to progressive psychomotor regression for 2.5 years. Motor function regression was the main manifestation in the early stage, and brain MRI and whole-exome sequencing (WES) of the family showed no abnormalities. After the age of 4 years and 9 months, the boy developed cognitive function regression, and brain MRI showed cerebellar atrophy. The reanalysis of WES results revealed a compound heterozygous mutation, [NM_000520, c.784C>T(p.His262Tyr]), c.1412C>T(p.Pro471Leu)], in the HEXA gene. The enzyme activity detection showed a significant reduction in the level of β-hexosaminidase encoded by this gene. The boy was diagnosed with juvenile Tay-Sachs disease (TSD). TSD has strong clinical heterogeneity, and cerebellar atrophy may be an important clue for the diagnosis of juvenile TSD. The reanalysis of genetic data when appropriate based on disease evolution may improve the positive rate of WES.

Key words

Gangliosidosis / Tay-Sachs disease / HEXA gene / Cerebellar atrophy / Child

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

TIAN Mao-Qiang, CHEN Xiao-Xi, LI Lei, LANG Chang-Hui, LI Juan, CHEN Jing, YU Xiao-Hua, SHU Xiao-Mei. Progressive psychomotor regression for 2.5 years in a boy aged 5 years[J]. Chinese Journal of Contemporary Pediatrics. 2022, 24(6): 699-704 https://doi.org/10.7499/j.issn.1008-8830.2201048

References

1 李清峰, 郁莉斐. 被误诊为重症肌无力3例病例分析[J]. 中华实用儿科临床杂志, 2021, 36(3): 222-224. DOI: 10.3760/cma.j.cn101070-20191106-01098.
2 杨昌键, 雷文婷, 余小华, 等. 表型不同的酪氨酸羟化酶缺乏症2例[J]. 中华实用儿科临床杂志, 2020, 35(19): 1509-1511. DOI: 10.3760/cma.j.cn101070-20190705-00602.
3 Mascalchi M, Mari F, Berti B, et al. Fast progression of cerebellar atrophy in PLA2G6-associated infantile neuronal axonal dystrophy[J]. Cerebellum, 2017, 16(3): 742-745. PMID: 28091863. DOI: 10.1007/s12311-017-0843-z.
4 Langer Y, Aran A, Gulsuner S, et al. Mitochondrial PITRM1 peptidase loss-of-function in childhood cerebellar atrophy[J]. J Med Genet, 2018, 55(9): 599-606. PMID: 29764912. DOI: 10.1136/jmedgenet-2018-105330.
5 Regier DS, Kwon HJ, Johnston J, et al. MRI/MRS as a surrogate marker for clinical progression in GM1 gangliosidosis[J]. Am J Med Genet A, 2016, 170(3): 634-644. PMID: 26646981. DOI: 10.1002/ajmg.a.37468.
6 Hoffmann GF, Charpentier C, Mayatepek E, et al. Clinical and biochemical phenotype in 11 patients with mevalonic aciduria[J]. Pediatrics, 1993, 91(5): 915-921. PMID: 8386351.
7 Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology[J]. Genet Med, 2015, 17(5): 405-424. PMID: 25741868. PMCID: PMC4544753. DOI: 10.1038/gim.2015.30.
8 杨志刚, 王媛, 陈国洪. Tay-Sachs病1例临床及HEXA基因突变分析[J]. 临床儿科杂志, 2019, 37(9): 697-699. DOI: 10.3969/j.issn.1000-3606.2019.09.015.
9 Shaimardanova AA, Chulpanova DS, Solovyeva VV, et al. Functionality of a bicistronic construction containing HEXA and HEXB genes encoding β-hexosaminidase A for cell-mediated therapy of GM2 gangliosidoses[J]. Neural Regen Res, 2022, 17(1): 122-129. PMID: 34100447. PMCID: PMC8451576. DOI: 10.4103/1673-5374.314310.
10 Leal AF, Benincore-Flórez E, Solano-Galarza D, et al. GM2 gangliosidoses: clinical features, pathophysiological aspects, and current therapies[J]. Int J Mol Sci, 2020, 21(17): 6213. PMID: 32867370. PMCID: PMC7503724. DOI: 10.3390/ijms21176213.
11 Jahnová H, Poupětová H, Jire?ková J, et al. Amyotrophy, cerebellar impairment and psychiatric disease are the main symptoms in a cohort of 14 Czech patients with the late-onset form of Tay-Sachs disease[J]. J Neurol, 2019, 266(8): 1953-1959. PMID: 31076878. DOI: 10.1007/s00415-019-09364-3.
12 Májovská J, Hennig A, Nestrasil I, et al. Pontocerebellar atrophy is the hallmark neuroradiological finding in late-onset Tay-Sachs disease[J]. Neurol Sci, 2022, 43(5): 3273-3281. PMID: 34800199. DOI: 10.1007/s10072-021-05757-3.
13 Reetz K, Rodríguez-Labrada R, Dogan I, et al. Brain atrophy measures in preclinical and manifest spinocerebellar ataxia type 2[J]. Ann Clin Transl Neurol, 2018, 5(2): 128-137. PMID: 29468174. PMCID: PMC5817824. DOI: 10.1002/acn3.504.
14 Rochtus A, Olson HE, Smith L, et al. Genetic diagnoses in epilepsy: the impact of dynamic exome analysis in a pediatric cohort[J]. Epilepsia, 2020, 61(2): 249-258. PMID: 31957018. PMCID: PMC7404709. DOI: 10.1111/epi.16427.
15 Li J, Gao K, Yan H, et al. Reanalysis of whole exome sequencing data in patients with epilepsy and intellectual disability/mental retardation[J]. Gene, 2019, 700: 168-175. PMID: 30904718. DOI: 10.1016/j.gene.2019.03.037.
16 Marshall J, Nietupski JB, Park H, et al. Substrate reduction therapy for Sandhoff disease through inhibition of glucosylceramide synthase activity[J]. Mol Ther, 2019, 27(8): 1495-1506. PMID: 31208914. PMCID: PMC6697407. DOI: 10.1016/j.ymthe.2019.05.018.
17 Wada R, Tifft CJ, Proia RL. Microglial activation precedes acute neurodegeneration in Sandhoff disease and is suppressed by bone marrow transplantation[J]. Proc Natl Acad Sci U S A, 2000, 97(20): 10954-10959. PMID: 11005868. PMCID: PMC27130. DOI: 10.1073/pnas.97.20.10954.
18 Stepien KM, Lum SH, Wraith JE, et al. Haematopoietic stem cell transplantation arrests the progression of neurodegenerative disease in late-onset Tay-Sachs disease[J]. JIMD Rep, 2018, 41: 17-23. PMID: 29214523. PMCID: PMC6122053. DOI: 10.1007/8904_2017_76.
19 Matsuoka K, Tamura T, Tsuji D, et al. Therapeutic potential of intracerebroventricular replacement of modified human β-hexosaminidase B for GM2 gangliosidosis[J]. Mol Ther, 2011, 19(6): 1017-1024. PMID: 21487393. PMCID: PMC3129794. DOI: 10.1038/mt.2011.27.
20 Golebiowski D, van der Bom IMJ, Kwon CS, et al. Direct intracranial injection of AAVrh8 encoding monkey β-N-acetylhexosaminidase causes neurotoxicity in the primate brain[J]. Hum Gene Ther, 2017, 28(6): 510-522. PMID: 28132521. PMCID: PMC5488349. DOI: 10.1089/hum.2016.109.
21 Gray-Edwards HL, Randle AN, Maitland SA, et al. Adeno-associated virus gene therapy in a sheep model of Tay-Sachs disease[J]. Hum Gene Ther, 2018, 29(3): 312-326. PMID: 28922945. DOI: 10.1089/hum.2017.163.
22 Shaimardanova AA, Chulpanova DS, Solovyeva VV, et al. Serum cytokine profile, beta-hexosaminidase A enzymatic activity and GM2 ganglioside levels in the plasma of a Tay-Sachs disease patient after cord blood cell transplantation and curcumin administration: a case report[J]. Life (Basel), 2021, 11(10): 1007. PMID: 34685379. PMCID: PMC8539434. DOI: 10.3390/life11101007.