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Autosomal recessive ataxias (ARAs) are a heterogeneous group of inherited neurodegenerative disorders that affect the cerebellum, the spinocerebellar tract, and/or the sensory tracts of the spinal cord. This study is aimed at establishing molecular classification and phenotypic correlation of childhood-onset ARAs in Southeast Anatolia of Turkey. Sixty-five children (aged 0 to 18) from 40 unrelated families who were analyzed through hereditary ataxia NGS panel between the years of 2015–2018 were selected for the study. Seventeen different, clinically significant ARA-related pathogenic variants were detected in 33 of 40 families (82.5%), 12 of which were noted to be unreported variants. Among these 33 families, 24 had ATM-related (72.72%), four had SACS-related (12.12%), three had COQ8A-related (9.09%), and two had APTX-related (6.06%) pathogenic variants. The c.3576G>A (p.K1192=) was the most common homozygous pathogenic ATM variant (33.33%) that was associated with milder phenotype of ataxia telangiectasia (AT) with the onset of age of 3. Patients with SACS variants demonstrated developmental delay and progressive ataxia before the age of 3. Slowly progressive ataxia and intellectual disability were the common clinical manifestations of the patients with homozygous c.1396delG (p. E466Rfs*11) pathogenic variant in COQ8A. Homozygous APTX c.689T>G (p.V230G) pathogenic variant was identified in two patients who had chief complaint of ataxic gait onset after puberty. The most common types of ARAs in this region are AT- and Charlevoix-Saguenay-type spastic ataxia. ATM gene analysis should be performed foremost on children presenting early-onset ataxia from Southeastern Anatolia. If there is a concomitant peripheral neuron involvement, SACS gene analysis should be preferred. This valuable data will be a guide for the first step molecular diagnostic approach before requesting the NGS panel for ARA. [ABSTRACT FROM AUTHOR]

Objective: Recessive mutations in the Gap Junction Protein Gamma 2 (GJC2) gene cause Pelizaeus-Merzbacher-like disease type 1, a severe infantile-onset hypomyelinating leukodystrophy. Milder, late-onset phenotypes including complicated spastic paraplegia in one family (SPG44), and mild tremor in one case, were reported associated to GJC2 homozygous missense mutations. Here, we report a new family with two siblings carrying a different homozygous GJC2 mutation, presenting with late-onset ataxic and pyramidal disturbances, and parkinsonism in one of them.Methods: Two affected siblings were studied by neurological examination and brain MRI. Genetic analyses included genome-wide homozygosity mapping in both siblings, and whole exome sequencing in one sib. The resulting candidate gene variant was validated by Sanger sequencing.Results: The affected siblings share a novel homozygous GJC2 missense mutation (c.820G>C, p.Val274Leu), predicted as pathogenic by all used in-silico tools. Brain MRI showed hyperintense signal in T2-weighted images in the internal capsule and subcortical and periventricular white matter, consistent with hypomyelination.Conclusions: Our findings confirm and further expand the late-onset phenotypes of GJC2 mutations, to include prominent ataxia, pyramidal disturbances and mild parkinsonism, and confirm the distinctive associated MRI pattern. [ABSTRACT FROM AUTHOR]

Hereditary spastic paraplegias (HSPs) are a genetically and clinically heterogeneous group of upper motor neuron disorders. Although the primary feature of HSP is lower extremity weakness ("uncomplicated" form), sequelae and clinical features of this disorder may include other neurological deficits such as dementia, neuropathy, retinopathy, mental retardation, and seizures ("complicated" form). To date, more than 56 different genetic loci and 41 HSP-related genes have been described as causative for autosomal dominant, recessive or X-linked HSP. One such locus on chromosome 15q, also known as locus SPG11 (OMIM 604360), has been shown to link to a complicated autosomal recessive form of disease known as HSP with thin corpus callosum (HSP-TCC). Herein we describe the identification and clinical presentation of a new family from Eastern Turkey with autosomal recessive HSP associated with mental retardation, epilepsy and a thinned corpus callosum on MRI. Using array-based SNP genotyping, we demonstrate linkage to the SPG11 locus on chromosome 15q13-15. Array-based copy number variation (CNV) analysis was also performed. Our results not only expand the phenotypic heterogeneity associated with the SPG11 locus to include an earlier age of onset with epilepsy, but also confirm the linkage to a 13 Mbp interval on chromosome 15q. This data, when added to those previously reported, support the notion that SPG11 is a phenotypically and genetically heterogeneous disorder. [ABSTRACT FROM AUTHOR]

The aim of the study was to investigate social competence in children with orthopaedic disability and its concurrent relations to child’s temperament, health condition, and maternal warmth. Participants were 68 Turkish children (mean = 5.94 years) with chronic orthopaedic disability and their mothers coming from disadvantaged backgrounds. Mother ratings were used to measure social competence, temperament, general health condition, and parental warmth. The attending physician rated the severity of orthopaedic disability. Attentional focusing, emotional reactivity, and child’s sex significantly predicted social competence. Age at first operation was slightly negatively associated with reactivity. The findings revealed the importance of emotional and attentional regulation for social functioning in children with orthopaedic disability, and pointed to the susceptibility of reactivity to environmental conditions. The study suggested that social functioning of youth with orthopaedic disability might benefit from temperament-based intervention and prevention programmes. [ABSTRACT FROM AUTHOR]

Inherited metabolic diseases are mainly caused by a genetic defect in the production or function of one of the proteins in the body. These diseases often present in early infancy with life-threatening metabolic decompensation attacks. In most cases vital organs such as the CNS, eye, liver, spleen, kidney, heart, and musculoskeletal system can be involved. Because metabolic diseases have an autosomal recessive inheritance, countries with a high prevalence of consanguineous marriages have a high incidence of these diseases. For example, the prevalence of phenylketonuria in Japan is 1: 108,822 and in the United States is 1: 10,000. Turkey, with an incidence of 1: 6,000, and Iran, with an incidence of 1: 4,698, are among the countries with the highest incidence of phenylketonuria. Nutrition management and nutrition therapy in patients with inherited metabolic diseases are very important and vital. Therefore, the diet of this group of patients needs careful and continuous analysis and follow-up. Since cell phones are used by many people on a daily basis, using mobile applications can be an effective and cost-effective way to adjust and follow the diet of this group of patients. In this regard, several applications have been designed to help people with metabolic diseases. These applications allow patients to set reminders to remind them of protein substitutes, follow-up their protein intake, record their protein metabolites levels in their blood, and send reports to their nutritionist and health professional. These Apps have been shown to save time and money. They can also help the health care system in many situations, such as pandemic conditions (ex: COVID-19 pandemic), inability of the patient to go to medical centers due to financial problems or long distances and other problems. Therefore, using mobile-health in hereditary metabolic patients can be very helpful as a companion guide for these patients. [ABSTRACT FROM AUTHOR]