Background: Autosomal recessive severe congenital neutropenia (SCN) has been associated with homozygous variants in the HAX1(HCLS1 Associated Protein X-1) gene. In this rare disease, ovarian insufficiency has been reported only in nine female patients in the literature. There is insufficient data on the gonadal function of patients with SCN due to HAX1 gene variant ( HAX1-SCN ) in childhood and the age of onset of premature ovarian insufficiency (POI) is unknown. The aim of this cross-sectional study was to evaluate the gonadal functions and pubertal development in pediatric patients with HAX1-SCN. Methods: Forty-five patients, including 24 females (median age 11.3 years, 1.5–31 years, 13 pubertal and 11 prepubertal), and 21 males (median age 9.5 years, 3–18.8 years, 7 pubertal and 14 prepubertal), followed in 7 centers, were included. POI is defined as a menstrual disturbance with increased follicle stimulating hormone (FSH) and low anti-Mullerian hormone (AMH). We classified prepubertal female patients as impending POI when they had low AMH and high FSH values, indicating impaired ovarian function. Results: A homozygous single nucleotide insertion (position 130-131insA) leading to a premature stop codon; p.Trp44*(c.132G>A) variant in HAX1 gene was detected in 42 (93.3%) affected individuals. Other homozygous variants were p.Arg86*(c.256C>T) and p.Glu60Aspfs*25(c.180delA). We detected elevated serum FSH levels in 10/11 (90.9%) of prepubertal female patients, supporting the diagnosis of impending POI, and in 12/13 (92.3%) of pubertal female patients, classifying them as POI. All female patients had low AMH levels. Male patients did not exhibit gonadal insufficiency. Conclusions: This is the first and largest case series covering early childhood to evaluate patients with HAX1-SCN for gonadal functions. It has been observed that pubertal girls develop POI, prepubertal girls are at increased risk for gonadal failure and male patients are not affected. Our results suggest that HAX1 has an important role in ovarian maturation and/or function. The genotype-phenotype relationship of these patients and the effect of clinical features of SCN on gonadal function should be further investigated.

Objectives: In this study, it was aimed to determine the prevalence and clinical features of obesity and metabolic syndrome, which are long-term effects of survivors after treatment in children with leukemia and lymphoma. Patients&Method: Patients with leukemia and lymphoma, who were diagnosed between 2000 and 2012 (at least 2 two years after remission) were included. Data obtained through reviewing the family history, demographic characteristics, anthropometric measurements, and laboratory parameters (blood glucose, lipid, and insulin levels) were analyzed and compared at the time of diagnosis, after the treatment and at time of the study. Results: Eighty nine patients (45 boys, 44 girls) were included (mean age: 14.7 ± 4.3 years): 77.5% had acute lymphoblastic leukemia, 11.2% had acute myeloid leukemia, and 11.2% had lymphoma. Overall, 46% patients had received radiotherapy, 7% had undergone surgery, and 2.2% had received stem cell transplantation in addition to chemotherapy. The mean duration of treatment was 2.4 years, and the time elapsed after treatment was 4.9 years. While only one had obesity at the diagnosis, a significant increase in obesity (20%), hypertension (15.7%), hyperglycemia (15%), insulin resistance (35%) were observed at the time of study, and family history of hypertension, dyslipidemia, and cardiovascular diseases were significantly higher in this subgroup. Conclusion: The prevalence of metabolic syndorme is higher in children with leukemia and lymphoma after treatment, and begins to increase with the initiation of treatment and continues to increase over time. These children should be followed-up for late-effects including metabolic syndrome through life-long period.