Large doses of intravenous Rh (D) immunoglobulin lead to sustained elevations in Rh antibody titers

Rhesus (Rh) alloimmunization is potentially devastating for reproductive health. Rarely, RhD mismatched blood may be transfused accidentally, increasing the risks of RhD sensitization. Prevention of Rh sensitization is important especially in women of reproductive age group. Treatment with intravenous RhIg is potentially safe and also the effective means of preventing Rh alloimmunization in cases of Rh-mismatched blood transfusion. We report a case that illustrates the significantly high RhD antibody titers following treatment with intravenous Rh immunoglobulin for prevention of alloimmunization. An 18yo Rh-negative G0 had mistakenly received four units of Rh-positive blood. To avoid future pregnancy related complications, she received monotherapy with 13,200 μg total of intravenous Rh immunoglobulin (RhIg). The treatment was well tolerated; however the RhD antibody titers reached a peak of 1:512. The high levels of RhD antibody titers can have grave implications if the patient is pregnant

Novel mutation in COL1A1 associated with Osteogenesis imperfecta not compatible with life

Osteogenesis imperfecta (OI) is a skeletal dyscrasia characterized by decreased bone strength and associated fractures. Over 95% of autosomal dominant forms of this disease are associated with defects in the genes for collagen COL1A1 and COL1A2.1 The lethal type II disease has been identified antenatally by symmetrically shortened long bones and micromelia. Many reports have indicated that a femur length to abdominal circumference ratio (FL:AC) of less than 0.16 is predictive of lethality associated with OI.2,3 We report a case that presented at 20 weeks’ gestation with shortening of the lower limbs, specifically a lagging femur length and FL:AC of < 0.16. On subsequent ultrasound examinations, progressive shortening of the femur as well as shortening of the long bones of the upper extremities was documented. The thorax appeared normal until 31 weeks. The FL:AC remained below 0.16 throughout pregnancy. Workup in the neonatal period identified a novel mutation in COL1A1. The neonate was able to breathe spontaneously at birth requiring minimal respiratory support for the initial 2 weeks and lived for 26 days

Novel mutation in COL1A1 associated with Osteogenesis imperfecta not compatible with life

Osteogenesis imperfecta (OI) is a skeletal dyscrasia characterized by decreased bone strength and associated fractures. Over 95% of autosomal dominant forms of this disease are associated with defects in the genes for collagen COL1A1 and COL1A2.1 The lethal type II disease has been identified antenatally by symmetrically shortened long bones and micromelia. Many reports have indicated that a femur length to abdominal circumference ratio (FL:AC) of less than 0.16 is predictive of lethality associated with OI.2,3 We report a case that presented at 20 weeks’ gestation with shortening of the lower limbs, specifically a lagging femur length and FL:AC of < 0.16. On subsequent ultrasound examinations, progressive shortening of the femur as well as shortening of the long bones of the upper extremities was documented. The thorax appeared normal until 31 weeks. The FL:AC remained below 0.16 throughout pregnancy. Workup in the neonatal period identified a novel mutation in COL1A1. The neonate was able to breathe spontaneously at birth requiring minimal respiratory support for the initial 2 weeks and lived for 26 days

Polycystic Ovary Syndrome Susceptibility Loci Inform Disease Etiological Heterogeneity

Polycystic ovary syndrome (PCOS) is a complex disorder with heterogenous phenotypes and unclear etiology. A recent phenotypic clustering study identified metabolic and reproductive subtypes of PCOS. We hypothesize that the heterogeneity of PCOS manifestations reflects different mechanistic pathways and can be identified using a genetic approach. We applied k-means clustering to categorize the genome-wide significant PCOS variants into clusters based on their associations with selected quantitative traits that likely reflect PCOS etiological pathways. We evaluated the association of each cluster with PCOS-related traits and disease outcomes. We then applied Mendelian randomization to estimate the causal effects between the traits and PCOS. Three categories of variants were identified: adiposity, insulin resistant, and reproductive. Significant associations were observed for variants in the adiposity cluster with body mass index (BMI), waist circumference and breast cancer, and variants in the insulin-resistant cluster with fasting insulin, glucose values, and homeostatic model assessment of insulin resistance (HOMA-IR). Sex hormone binding globulin (SHBG) has strong association with all three clusters. Mendelian randomization suggested a causal role of BMI and SHBG on PCOS. No causal associations were observed for PCOS on disease outcomes