Identification of the molecular etiology in rare congenital hemolytic anemias using next-generation sequencing with exome-based copy number variant analysis.

OBJECTIVES: In congenital hemolytic anemias (CHA), it is not always possible to determine the specific diagnosis by evaluating clinical findings and conventional laboratory tests. The aim of this study is to evaluate the utility of next-generation sequencing (NGS) and clinical-exome-based copy number variant (CNV) analysis in patients with CHA. METHODS: One hundred and forty-three CHA cases from 115 unrelated families referred for molecular analysis were enrolled in the study. Molecular analysis was performed using two different clinical exome panels in 130 patients, and whole-exome sequencing in nine patients. Exome-based CNV calling was incorporated into the traditional single-nucleotide variant and small insertion/deletion analysis pipeline for NGS data in 92 cases. In four patients from the same family, the PK Gypsy variant was investigated using long-range polymerase chain reaction. RESULTS: Molecular diagnosis was established in 86% of the study group. The most frequently mutated genes were SPTB (31.7%) and PKLR (28.5%). CNV analysis of 92 cases revealed that three patients had different sizes of large deletions in the SPTB and six patients had a deletion in the PKLR. CONCLUSIONS: In this study, NGS provided a high molecular diagnostic rate in cases with rare CHA. Analysis of the CNVs contributed to the diagnostic success.

Spontaneous epidural and subdural hematoma in a child with afibrinogenemia and postoperative management.

Congenital afibrinogenemia is a rare coagulation disorder that exhibits recessive inheritance. The prevalence of this disease is around 1 per 1 000 000, but it is increased in countries where consanguineous marriages are common. Umbilical cord bleeding during the neonatal period is generally the first manifestation of the disease, but a later age of onset is not uncommon. This disease may also be manifested by gastrointestinal, genitourinary, mucosal, muscular, articular, and intracranial bleeding during childhood. Intracranial hemorrhage is a rare condition, but it is the leading cause of death in patients with afibrinogenemia. In this report, we present the case of a 13-year-old female patient with afibrinogenemia who underwent an operation for spontaneous massive extradural and subdural hematoma.

Vitamin D deficiency in pregnant women and their neonates in spring time in western Turkey.

Although Turkey is located in a sunny region, vitamin D deficiency is still a serious health problem in pregnant women and their infants, especially among the low socio-economic status Turkish population. This study was carried out in order to measure serum 25-hydroxyvitamin D3 [25(OH)D] concentrations of the pregnant women in the last trimester and in their neonates at delivery and to determine the factors associated with maternal serum 25(OH)D concentrations. Among the patients visiting the Ege Obstetrics and Gynecology Hospital in the period March to May 2008, 258 healthy pregnant women ≥37 weeks of gestation were included in this study. The information on different characteristics such as the number of pregnancies and births, nutritional status, vitamin and mineral support during gestation, educational status, clothing style and the economic level of the family was collected from women. Blood samples from the mothers and umbilical cord of the newborns were taken to measure 25(OH)D. The mean 25(OH)D concentrations of the mothers and their infants were 11.5 ± 5.4 ng/mL and 11.5 ± 6.8 ng/mL, respectively. We found a strong positive correlation between maternal serum and umbilical cord blood 25(OH)D concentrations (r = 0.651, P < 0.001). The concentration of 25(OH)D was ≤20 ng/mL in 233 mothers (90.3%) and ≤10 ng/mL in 130 mothers (50.4%). Maternal serum 25(OH)D concentrations related strongly to factors such as uncovered dressing style, sufficient consumption of dairy products and multivitamin use during gestation (P < 0.05). About half (52.7%) of these women had a covered dressing style. 25(OH)D concentrations of these covered dressing mothers and their infants were 9.7 ± 5.1 ng/mL and 9.7 ± 5.6 ng/mL, respectively, which were significantly lower compared with those of uncovered mothers and their babies (P < 0.001). This study showed that, despite a sunny environment, vitamin D deficiency and insufficiency are highly prevalent among the mothers and their neonates. This is generally due to the life style and nutritional status of the mothers. These findings suggest that much more effective vitamin D prophylaxis programmes should be implemented for pregnant women as well as for their babies.

Vitamin B12 and folate statuses are associated with diet in pregnant women, but not with anthropometric measurements in term newborns.

OBJECTIVE: To investigate the frequencies of vitamin B12 and folate deficiencies in pregnant women in low socioeconomic group, the relation between the animal-source foods consumption and maternal vitamin B12-folate statuses, and their impacts on anthropometric measurements of the infants. METHODS: A total of 208 pregnant women in the last trimester were included in the study. A questionnaire about socio-demographic status, consumption of meat, egg, milk-dairy products, multivitamin supplementation was used. Vitamin B(12) and folate concentrations were studied by chemiluminescence method. The babies of Vitamin B(12) deficient mothers were evaluated after birth. RESULTS: The rate of vitamin B(12) deficiency was 47.6% and folate deficiency was 17.3% of pregnant women. Animal food consumption was inadequate about half of pregnant women and vitamin B(12) levels in these women were significantly low. There were no statistically significant relationships between the birth weight, birth length and head circumference measurements, and maternal vitamin B(12) and folate concentrations. CONCLUSION: The rate of vitamin B12 deficiency in pregnant women in low socioeconomic population is high. Although there were no significant effects of the vitamin B12 and folate deficiencies on birth size, additional studies are required to elucidate the subsequent effects.