Clinical and Laboratory Profile of Gangliosidosis from Southern Part of India

Abstract

Gangliosidoses are progressive neurodegenerative disorders caused by the deficiency of enzymes involved in the breakdown of glycosphingolipids. There are not much data about gangliosidosis in India; hence, this study was planned. The aim is to study the clinical, biochemical, and molecular profile of gangliosidosis. A retrospective chart review, in the pediatric neurology department from January 2015 to March 2020, was performed. Children diagnosed with Gangliosidosis were included. The disorder was confirmed by reduced activity of enzymes and/or pathogenic or likely pathogenic variants in associated genes. We assessed age at presentation, gender, parental consanguinity, clinical manifestations, neuroimaging findings, enzyme level, and pathogenic or likely pathogenic variants. Clinical data for 32 children with gangliosidosis were analyzed, which included 12 (37.5%) with GM1 gangliosidosis, 8 (25%) with Tay-Sachs disease (TSD), 11 (34.37%) with Sandhoff disease (SD), and 1 AB variant of GM2 gangliosidosis that occurs due to GM2 ganglioside activator protein deficiency. Twenty-four (75%) children were the offspring of consanguineous parents. Thirty-one (97%) had developmental delay. The median age at presentation was 15.5 months. Nine (28.12%) had seizures. Five children (41.6%) with GM1 gangliosidosis and two with SD had extensive Mongolian spots. Ten children with GM1 gangliosidosis (83.3%) had coarse facial features. Cherry red spot was found in 24 out of 32 children (75%). All children with GM1 gangliosidosis and none with TSD had hepato-splenomegaly. Two children (2/8; 25%) with TSD and seven (7/11; 63%) with SD had microcephaly. One child with SD had coarse facies and three did not have hepato-splenomegaly. Neuroimaging findings revealed bilateral thalamic involvement in 20 (62.5%) patients and periventricular hypomyelination in all cases. One child had a rare AB variant of GM2 gangliosidosis. GM2 Gangliosidoses are more common compared with GM1 variety. All of them had infantile onset except one child with TSD. Microcephaly can be present while usually megalencephaly is reported in the literature. The absence of hepato-splenomegaly does not rule out SD. Extensive Mongolian spots can be seen in GM2 gangliosidosis. AB variant of GM2 gangliosidosis should be considered when the enzyme is normal in the presence of strong clinical suspicion.

Keywords

GM1 gangliosidosis - GM2 gangliosidosis - Tay-Sachs disease - Sandhoff disease - lysosomal storage disorders

Authors' Contributions

V.K.G. dedicated to supervision, guidance, and review of the manuscript. P.G. and N.B. involved in the management of the children and the preparation of the manuscript. M.B. supported in the diagnosis and the preparation of the manuscript. S.K.S. and N.B. provided valuable inputs in the management of children.

Publikationsverlauf

Eingereicht: 28. Juni 2020

Angenommen: 13. September 2020

Artikel online veröffentlicht:
19. Oktober 2020

• References

• 1 Regier DS, Kwon HJ, Johnston J. et al. MRI/MRS as a surrogate marker for clinical progression in GM1 gangliosidosis. Am J Med Genet A 2016; 170 (03) 634-644
• 2 Kaback MM, Desnick RJ. Hexosaminidase: a deficiency. 1999. Mar 11 [Updated 2011 Aug 11]. In: Adam MP, Ardinger HH, Pagon RA. et al., eds. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020
• 3 Frey LC, Ringel SP, Filley CM. The natural history of cognitive dysfunction in late-onset GM2 gangliosidosis. Arch Neurol 2005; 62 (06) 989-994
• 4 Regier DS, Tifft CJ. GLB1-related disorders. InGeneReviews® [Internet]. University of Washington, Seattle; 2019
• 5 Weissbluth M, Esterly NB, Caro WA. Report of an infant with GM1 gangliosidosis type I and extensive and unusual mongolian spots. Br J Dermatol 1981; 104 (02) 195-200
• 6 Selsor LC, Lesher Jr JL. Hyperpigmented macules and patches in a patient with GM1 type 1 gangliosidosis. J Am Acad Dermatol 1989; 20 (5 Pt 2): 878-882
• 7 Dweikat I, Libdeh BA, Murrar H, Khalil S, Maraqa N. Gm1 gangliosidosis associated with neonatal-onset of diffuse ecchymoses and mongolian spots. Indian J Dermatol 2011; 56 (01) 98-100
• 8 Vaidyanathan S, Kurup RP, Kumar Iv A, Nampoothiri S. Extensive Mongolian spots as a clue in GM1 gangliosidosis: Report of two cases. J Pediatr Neurol 2009; 7 (04) 411-414
• 9 Tuteja M, Bidchol AM, Girisha KM, Phadke S. White matter changes in GM1 gangliosidosis. Indian Pediatr 2015; 52 (02) 155-156
• 10 Bidchol AM, Dalal A, Trivedi R. et al. Recurrent and novel GLB1 mutations in India. Gene 2015; 567 (02) 173-181
• 11 Feng Y, Huang Y, Zhao X. et al. Clinical and molecular characteristics of 11 Chinese probands with GM1 gangliosidosis. Metab Brain Dis 2018; 33 (06) 2051-2057
• 12 Karimzadeh P, Naderi S, Modarresi F. et al. Case reports of juvenile GM1 gangliosidosisis type II caused by mutation in GLB1 gene. BMC Med Genet 2017; 18 (01) 73
• 13 Karimzadeh P, Jafari N, Nejad Biglari H. et al. GM2-Gangliosidosis (Sandhoff and Tay Sachs disease): diagnosis and neuroimaging findings (an Iranian pediatric case series). Iran J Child Neurol 2014; 8 (03) 55-60
• 14 Smith NJ, Winstone AM, Stellitano L, Cox TM, Verity CM. GM2 gangliosidosis in a UK study of children with progressive neurodegeneration: 73 cases reviewed. Dev Med Child Neurol 2012; 54 (02) 176-182
• 15 Bley AE, Giannikopoulos OA, Hayden D, Kubilus K, Tifft CJ, Eichler FS. Natural history of infantile G(M2) gangliosidosis. Pediatrics 2011; 128 (05) e1233-e1241
• 16 Er E, Canda E, Eraslan C, Sözmen E, Uçar SK, Çoker M. An evaluation of the demographic and clinical characteristics of patients with GM2 gangliosidosis. J Pediatric Research 2018; 5 (01) 12
• 17 McGovern MM, Desnick RJ. Lipidoses (Lysosomal Storage Disorders). Nelson Textbook of Pediatrics 20th ed. 2007; 86 (04) 705-706
• 18 Gowda VK, Amoghimath R, Srinivasan VM, Bhat M. Sandhoff disease without hepatosplenomegaly due to hexosaminidase B gene mutation. J Pediatr Neurosci 2017; 12 (01) 78-79
• 19 Ozkara HA, Topçu M, Renda Y. Sandhoff disease in the Turkish population. Brain Dev 1997; 19 (07) 469-472
• 20 Maulik K, Kumar S, Singh P, Saini AG. Microcephaly in infantile Sandhoff's disease. BMJ Case Rep 2017; 2017: bcr-2017
• 21 Gowda VK, Srinivasan VM, Bhat M, Benakappa A. Tay-Sachs disease presenting as refractory epilepsy with autistic regression secondary to a novel mutation in HEXA gene. Indian J Pediatr 2018; 85 (12) 1134-1135
• 22 Renaud D, Brodsky M. GM2-gangliosidosis, AB variant: clinical, ophthalmological, MRI, and molecular findings. JIMD Rep 2016; 25: 83-86
• 23 Sheth J, Datar C, Mistri M, Bhavsar R, Sheth F, Shah K. GM2 gangliosidosis AB variant: novel mutation from India - a case report with a review. BMC Pediatr 2016; 16: 88