Infantile Onset Spinocerebellar Ataxia 2 (SCA2)

Abstract

Autosomal dominant cerebellar ataxia type I is a heterogeneous group of spinocerebellar ataxias with variable neurologic presentations, with age of onset varying from infancy to adulthood. Autosomal dominant cerebellar ataxia type I is composed mainly of 3 prevalent spinocerebellar ataxia types with different pathogenic loci, specifically spinocerebellar ataxia 1 (6p24-p23), spinocerebellar ataxia 2 (12q24.1), and spinocerebellar ataxia 3 (14q32.1). The shared pathogenic mutational event is the expansion of the CAG repeat that results in polyglutamine extended stretches in the encoded proteins. CAG repeat disorders generally show the phenomenon of anticipation, which is more often associated with paternal transmission. In this report, we describe a patient with infantile-onset spinocerebellar ataxia type 2 (~320 CAG repeat) who inherited the disease from his father (47 CAG repeats). We have summarized the clinical, neuroimaging, electroencephalographic (EEG), and molecular data of previous cases and attempt to highlight the most consistent findings. Our intent is to help treating clinicians to suspect this disorder and to offer timely genetic counseling for a currently potentially untreatable disorder.

A novel nine base deletion mutation in NADH-cytochrome b5 reductase gene in an Indian family with recessive congenital methemoglobinemia-type-II

“…The patient had improvement in cyanosis that may be due to the initiation of daily ascorbic acid therapy. It has been hypothesized that a possible response to ascorbic acid may be related to the effect of making additional ferrous iron available for its role as a cofactor in carnitine synthesis [7]. Our patient had a methemoglobin level of 61.1% and was treated with methylene blue (0.5 mg/kg body weight).…”

The Multiple Faces of Spinocerebellar Ataxia type 2

“…Death occurs early. Brain MRI showed extreme cerebellar and brainstem atrophy, but also different degrees of supratentorial atrophy and ventricular enlargement, and white matter signal abnormalities likely attributable to dysmyelination and/or delayed myelination 70, 71, 72, 73…”

A clinical report of the massive CAG repeat expansion in spinocerebellar ataxia type 2: Severe onset in a Mexican child and review previous cases

“…An infantile onset is an uncommon occurrence presentation with only nine reports in the literature and is associated with extremely large CAG expansions (range 100–200 repeats). On the other hand, there are severe infantile cases with expansions between 50-70 repeats, sometimes is related with interruption CTG or CAA as occurs in adults with SCA2 and amyotrophic lateral sclerosis, which also leads to instability of ATXN2 mRNA ( Choudhry et al , 2001 ; Antenora et al , 2017 ), and meiotic instability a general feature of SCA2 without a familial history ( Babovic et al , 1998 ; Mao et al , 2002 ; Moretti et al , 2004 ; Dirik et al , 2007 ; Abdel and Zaki, 2008 ; Paciorkowski et al , 2011 ; Di Fabio et al , 2012 ; Vinther-Jensen et al , 2013 ; Singh et al , 2014 ). However, cases with infantile SCA2 are explain by these features; there are childhood onset cases reported with mosaicism in germ cells such as spermatozoa with larger expanded alleles more than in peripheral blood cells ( Moretti et al , 2004 ; Dirik et al , 2007 ; Abdel and Zaki, 2008 ; Vinther-Jensen et al , 2013 ).…”

“…The most frequent signs in infantile onset are developmental delay, visual impairment usually dependent on retinitis pigmentosa or optic atrophy, hypotonia, seizures with infantile spasms or myoclonic seizures, facial dysmorphism, dystonic features and early death ( Tables 1 and 2 ) ( Singh et al , 2014 ; Antenora et al , 2017 ). Brain MRI scans showed extreme cerebellar and brainstem atrophy, but also different degrees of supratentorial atrophy, ventricular enlargement, and white matter signal abnormalities probably attributable to dysmyelination and/or delayed myelination ( Singh et al , 2014 ; Antenora et al , 2017 ). The aim of this report is to present the clinical findings and molecular studies in a Mexican child with familial SCA2 with extremely large CAG expansion repeats, and a literature review of clinical and molecular findings in early-onset cases with SCA2.…”

“…So, the range in 19 reported cases with SCA2 with age of onset in childhood was 0-48 months, which were carriers of the heterozygous genotype (22/X), in which X corresponds to an allele with abnormal expansion repeats with an average range of 62-841 repeats ( Table 1 ) ( Babovic et al , 1998 ; Mao et al , 2002 ; Moretti et al , 2004 ; Dirik et al , 2007 ; Abdel and Zaki, 2008 ; Paciorkowski et al , 2011 ; Di Fabio et al , 2012 ; Vinther-Jensen et al , 2013 ; Avelino et al , 2014 ; Singh et al , 2014 ).…”