Leaders in Pharmaceutical Business Intelligence (LPBI) Group

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

Leptin is considered to have an important role in reproductive functions, including menstrual-cycle regulation, pregnancy, and lactation. The absence of leptin action caused by functional mutations in the leptin gene (LEP) or the leptin receptor gene (LEPR) has been linked to infertility in rodents and humans. A pregnancy was reported in a woman despite absent leptin signaling.

In 1998, it was reported the case of a morbidly obese patient with a rare homozygous LEPR mutation, which was shared by several affected siblings. The mutation was found in the patient’s blood and adipose tissue, indicating no evidence of chimerism. She had been followed for morbid obesity since early childhood, with abnormal compulsive-feeding behaviors and reduced levels of growth hormone and thyrotropin. She entered puberty late, with irregular cycles after the age of 17 years. Repeated evaluations of sex-hormone levels were considered to be normal after the age of 18 years. The patient underwent abdominoplasty at the age of 16 years and gastric-bypass surgery at the age of 24 years. Six months after gastric bypass, her weight had decreased from 220 kg (485 lb) to 170 kg (375 lb), with a concurrent decrease in the body-mass index (the weight in kilograms divided by the square of the height in meters) from 81 to 62. She was counseled regarding contraception and was prescribed oral contraceptives. Two years after gastric bypass, just before an unplanned pregnancy, she had no diabetes, hypertension, respiratory disorders, or other recognized complications of obesity.

Ultrasonographic examinations during pregnancy were considered normal except for suspected macrosomia in the third trimester. The patient’s total weight gain during pregnancy was 50 kg (110 lb) from a prepregnancy weight of 180 kg (397 lb). Routine screening for gestational diabetes was normal. Although occasional elevated blood sugar levels were documented during the pregnancy, the glycated hemoglobin level in the third trimester was 5.6%. At 37 weeks 5 days of gestation (on the basis of first-trimester ultrasonography), the patient delivered a son by elective cesarean section, which was performed because of breech presentation and suspected macrosomia under epidural anesthesia after the administration of glucocorticoids for fetal lung maturation. The birth weight was 3720 g (8.2 lb), and the length was 50 cm (19.7 in.); the head circumference was 36.5 cm (14.4 in.), which was above the 90th percentile. The patient’s postpartum course was complicated by a wound infection. The infant’s neonatal course was complicated by hypoglycemia, hypocalcemia, and jaundice requiring phototherapy. The patient briefly breast-fed her child. The child’s growth and development have been normal; his weight at 1 year was 14 kg (31 lb).

This case of a natural pregnancy in a woman with a homozygous LEPR mutation calls into question the belief that leptin function is critical to reproductive function.

Source References:

http://www.nejm.org/doi/full/10.1056/NEJMc1200116