The Complex Genetic Landscape of Hereditary Ataxias in Turkey and Implications in Clinical Practice.

BACKGROUND: The genetic and epidemiological features of hereditary ataxias have been reported in several populations; however, Turkey is still unexplored. Due to high consanguinity, recessive ataxias are more common in Turkey than in Western European populations. OBJECTIVE: To identify the prevalence and genetic structure of hereditary ataxias in the Turkish population. METHODS: Our cohort consisted of 1296 index cases and 324 affected family members. Polymerase chain reaction followed by Sanger sequencing or fragment analysis were performed to screen for the trinucleotide repeat expansions in families with a dominant inheritance pattern, as well as in sporadic cases. The expansion in the frataxin (FXN) gene was tested in all autosomal recessive cases and in sporadic cases with a compatible phenotype. Whole-exome sequencing was applied to 251 probands, selected based on the family history, age of onset, and phenotype. RESULTS: Mutations in known ataxia genes were identified in 30% of 1296 probands. Friedreich's ataxia was found to be the most common recessive ataxia in Turkey, followed by autosomal recessive spastic ataxia of Charlevoix-Saguenay. Spinocerebellar ataxia types 2 and 1 were the most common dominant ataxias. Whole-exome sequencing was performed in 251 probands with an approximate diagnostic yield of 50%. Forty-eight novel variants were found in a plethora of genes, suggesting a high heterogeneity. Variants of unknown significance were discussed in light of clinical data. CONCLUSION: With the large sample size recruited across the country, we consider that our results provide an accurate picture of the frequency of hereditary ataxias in Turkey. © 2021 International Parkinson and Movement Disorder Society.

Investigation of Nerve Conduction Studies of Carpal Tunnel Syndrome Cases With Different Risk Factors: An Electrodiagnostic Study.

PURPOSE: The aim of this study was to determine whether there are electrodiagnostic differences between carpal tunnel syndrome (CTS) patients with diabetes mellitus, CTS + hypothyroidism (HT), CTS + fibromyalgia syndrome, CTS + rheumatoid arthritis (RA), and idiopathic CTS cases, by comparing nerve conduction studies. METHODS: This research examined electrophysiologic studies of 47 untreated HT + CTS, 47 diabetes mellitus + CTS, 49 RA + CTS, 52 fibromyalgia syndrome + CTS, 50 idiopathic CTS cases, and a healthy control group of 50 individuals (a total of 293 patients and 433 hands with CTS). RESULTS: There were no significant differences between the groups in terms of sex and age. There was no significant difference between the CTS groups-in terms of numbers-with mild, moderate, and severe CTS. When the CTS groups were compared with the control group, in all CTS groups on both left and right hands, there was a significant prolongation in median motor latency and median sensory latency (in the 3rd finger); also a significant decrease in median sensory velocity in the 3rd finger. In diabetes mellitus, HT, and RA groups, the median motor amplitudes in both hands were significantly decreased compared with the idiopathic group. There was a moderate significant negative correlation between disease duration and median motor amplitudes (of both right and left sides) in RA (right; P = 0.028, r = 0.761, left; P = 0.041, r = 0.694) and HT groups (right; P = 0.035, r = 0.637, left; P = 0.049, r = 0.697). CONCLUSIONS: Electrodiagnostic results showed both demyelinating injury and axonal damage in diabetes mellitus, HT, and RA patients with CTS, in these patients during treatment for CTS. Early treatment planning should include the risk factor diseases.

Retrospective approach to methylenetetrahydrofolate reductase mutations in children.

Methylenetetrahydrofolate reductase reduces methyltetrahydrofolate, a cosubstrate in the remethylation of homocysteine, from methylenetetrahydrofolate. Congenital defects, hematologic tumors, and intrauterine growth retardation can occur during childhood. This study evaluated clinical and laboratory treatment approaches in children diagnosed with methylenetetrahydrofolate reductase mutations. Our group included 23 boys and 14 girls, aged 103.4 ± 70.8 months S.D. Clinical findings of patients and homocysteine, vitamin B12, folate, hemogram, electroencephalography, cranial magnetic resonance imaging, and echocardiography data were evaluated in terms of treatment approach. Our patients' findings included vitamin B12 at 400.4 ± 224.6 pg/mL S.D. (normal range, 300-700 pg/mL), folate at 10.1 ± 4.5 ng/mL S.D. (normal range, 1.8-9 ng/mL), and homocysteine at 8.4 ± 4.7 µmol/L S.D. (normal range, 5.5-17 µmol/L). Eighty-eight percent of patients demonstrated clinical findings. In comparisons involving categorical variables between groups, χ(2) tests were used. No relationship was evident between mutation type, laboratory data, and clinical severity. All mothers who had MTHFR mutations and had babies with sacral dimples had taken folate supplements during pregnancy. To avoid the risk of neural tube defects, pregnant women with a MTHFR mutation may require higher than normally recommended doses of folic acid supplementation for optimum health.

Intra-familial incidence and characteristics of hot water epilepsy.

OBJECTIVE: To assess the clinical features of several members of the same family diagnosed with both hot water epilepsy (HWE) and cerebral lesions. METHODS: Age at onset and types of seizure, precipitating factors, EEG findings, and neuroimages were evaluated. RESULTS: The family consisted of six generations, including one consanguineous parent. Of eight family members diagnosed with epilepsy, seven suffered from HWE. Age at onset of seizures ranged within childhood. Seven patients with HWE experienced complex partial seizures, with or without secondary generalization; one experienced simple partial seizures as well as complex partial seizures. Three patients experienced spontaneous seizures as well as HWE. Interictal EEG revealed abnormalities in two patients. Magnetic resonance imaging revealed cerebral lesions in one patient, probably attributable to ischemic changes. Magnetic resonance images were consistent with findings of ischemic gliosis in two patients, and either demyelinating or ischemic gliosis in one patient. CONCLUSIONS: Descriptions of HWE families with different ethnic backgrounds may permit more definite conclusions regarding the mechanisms epileptogenesis, and the genetic defects that underlie this disease.

Carpal tunnel syndrome in postmenopausal women.

OBJECTIVE: Hormonal changes that accompany menopause have a significant impact on the nervous and other physiological systems. Our objective was to evaluate the relationship between carpal tunnel syndrome (CTS) and the clinical features of menopause in postmenopausal women, in comparison to age-matched healthy controls. METHODS: Overall, 6230 women were seen during the study period. Of these, 5587 were not eligible because they were premenopausal or perimenopausal. 537 women did not meet the criteria used in the study for a diagnosis of idiopathic CTS and were excluded. Finally, one hundred and six patients with CTS and 115 controls were examined. The presence of CTS was confirmed both clinically and electrophysiologically. Socio-demographic variables and reproductive histories were evaluated via a structured interview. RESULTS: In comparison to healthy controls, patients with CTS showed a significantly greater number of pregnancies and an earlier age at menopause. Regarding the type of menopause, patients and controls showed similar frequencies for natural versus surgical menopause. The frequency of natural menopause was significantly higher than that of surgical menopause in both groups. CONCLUSION: Our results suggest that age at menopause may be a significant factor in the development of CTS. Pregnancy-related hormonal changes may have long-term effects that increase the incidence of CTS in postmenopausal women.