Bisphosphonate treatment at spondylo-ocular syndrome due to a novel compound heterozygote variant in XYLT2 and review of the literature.

Spondylo-ocular syndrome is a rare autosomal recessive disorder characterized by generalized osteoporosis, hearing loss, visual impairment due to cataract, and platyspondyly. Previous studies have revealed that the syndrome is caused by pathogenic variants in the XYLT2 gene. A patient with spondylo-ocular syndrome and two heterozygous pathogenic variant in the XYLT2 gene in compound state are described here. The patient presented with osteoporosis, platyspondyly, ocular findings, hearing loss, kyphosis, scoliosis, facial findings, intellectual disability, and undescended testicles. Previous reports of bisphosphonate treatment response were variable, whereas a long-term follow-up with bisphosphonate treatment in this case resulted in normalization of vertebral structures. Reporting such cases helps to determine the appropriate genotype-phenotype correlation in patients with XYLT2-related pathogenesis.

Benign transient hyperphosphatasemia in the pediatric population: a single center cohort study.

OBJECTIVES: Alkaline phosphatase (ALP) can be increased in a benign condition known as benign-transient hyperphosphatasemia (BTH). We aimed to evaluate the demographic, and clinical characteristics of infants and children with BTH. METHODS: In our retrospective study, infants and children diagnosed with BTH between September 2019 and September 2023 were included. RESULTS: Of 249 children with elevated ALP levels, 95 (38.1 %) had BTH. The mean age at diagnosis of children with BTH was 2.4 ± 1.3 years (min 0.6 - max 6.2 years). ALP mean value was 2,587 ± 1252 U/L (min 972 - max 5757 U/L). ALP value was an average 7.4 ± 3.6 times higher than the corresponding upper limit of normal. The second measurement was made after an average of 13.2 ± 6 days, and a statistically significant difference was detected compared to the first value, with a decrease of 61 ± 23 % in the ALP value (p<0.001). ALP value returned to normal in an average of 44 ± 29.2 days. Elevated ALP was detected during infection in 49 (51.6 %) children. When the sample was divided into those under 2 years of age and aged 2 and over, no statistical difference was observed in ALP levels in the time it took for ALP levels to return to the normal range (p=0.480). CONCLUSIONS: BTH should be kept in mind if high serum ALP is detected in children without clinical or laboratory suspicion of bone or liver disease. In the follow up detecting a significant decrease trend compared to the first value may be guiding for BTH.

Body mass index evolution and ovarian function in adolescent girls who received GnRH agonist treatment for central precocious puberty or early and fast puberty.

OBJECTIVES: Gonadotropin-releasing hormone agonist (GnRHa) has been used for central precocious puberty (CPP) or early and fast puberty. It was aimed to assess changes in body mass index (BMI), polycystic ovary syndrome (PCOS) frequency, and anti-Müllerian hormone (AMH) in girls who had been treated with GnRHa. METHODS: Fifty-eight adolescent girls treated with GnRHa for CPP or early and fast puberty (3.75 mg/28 days), between 2011 and 2015, were re-evaluated in 2020-2022 at least 2 years after menstruation. Hormonal analyses were compared with 51 healthy adolescents. RESULTS: In the GnRHa-treated group, a statistically significant increase was observed when the BMI standard deviation score (SDS) at the beginning of the treatment was compared with the BMI SDS at the end of the treatment (p=0.038). A statistically significant decrease was observed when the BMI SDS at the end of the treatment was compared with the BMI SDS in late adolescence (p=0.012). When the BMI SDS at the beginning of the treatment was compared with the BMI SDS in late adolescence, it was observed that there was no statistically significant difference (p=0.196). Of the 58 girls in the GnRHa-treated group, 8 (14 %) had PCOS. Serum AMH levels did not differ between the GnRHa-treated and the control group. CONCLUSIONS: GnRHa treatment causes no adverse effect on BMI, at least in late adolescence. Girls treated with GnRHa were not found to be prone to developing PCOS. AMH levels were similar in the GnRHa-treated group as in the control group.

Novel sphingosine-1-phosphate lyase mutation causes multisystemic diseases: case report.

BACKGROUND: Sphingosine phosphate lyase insufficiency syndrome (SPLIS) caused by inactivating mutations in the human SGPL1 gene results in congenital nephrotic syndrome, adrenal insufficiency, ichthyosis, immunodeficiency, and a wide range of pathological neurological features. We present a novel mutation in the SGPL1 gene causing hypocalcemia, primary adrenal insufficiency (PAI), nephrotic syndrome, subclinical hypothyroidism, lymphopenia, ptosis, and pathologic neuroimaging findings. CASE: A Turkish male infant presented with bruising at 2 months of age and was diagnosed with hypocalcemia, PAI, and subclinical hypothyroidism. At the age of 15 months, he was admitted to the hospital with ptosis. Other systemic manifestations included persistent lymphopenia and nephrotic syndrome. Magnetic resonance imaging (MRI) of the brain and orbit demonstrated asymmetric contrast enhancement in the left cavernosal sinus, orbital apex, and thinning at the bilateral optic nerve. Whole exome sequencing (WES) revealed a homozygous c.1432C > G (p.Gln478Glu) variant in the SGPL1 gene (NM_003901.4), which has not previously been reported in the literature. CONCLUSIONS: Novel mutations in SGPL1 are still being identified. This case reminded us that SPLIS should not be considered for patients with nephrotic syndrome alone. Still, PAI may also include patients with neurological disorders, hypocalcemia, and pathological neuroimaging findings such as thinning at the bilateral optic nerve.

Evaluation of Hypersensitivity Reactions with Leuprolide Acetate and Triptorelin Acetate in Children.

Introduction: Gonadotropin releasing hormone analogues (GnRHa) are commonly used to treat central precocious puberty (CPP). Generally, they are well-tolerated; however adverse reactions have been reported. Local adverse events occur in 10-15% of the patients who were treated with GnRHa. Anaphylactoid reactions with GnRHa are very rarely seen. The aim of this study is to report our clinical experience with hypersensitivity reactions seen in pediatric patients receiving leuprolide acetate (LA) and triptorelin acetate (TA) in CPP at the single pediatric tertiary medical center and to evaluate the incidence rate of hypersensitivity reactions. Methods: This retrospective study included children with CPP who were treated with GnRHa (LA and TA) at our hospital between January 2013 and December 2020. We analyzed clinical characteristics of patients who experienced adverse reactions and analyzed the incidence rate. Results: Seven side effects (adverse reactions) (0.69%) were observed among total of 1010 CPP patients who were treated with TA and LA. Sterile abscesses were observed in 3 patients (0.29%). None of the patients had an anaphylaxis. Tremors of both hands, a vomiting episode, an urticarial rash, and musculoskeletal stiffness were observed in one patient each. Conclusion: In our study, mild reactions were seen in 7 patients. GnRHa can be safely used and well-tolerated medications; but exceedingly rare, severe reactions can be developed.