In this study of perinatal and infantile hypophosphatasia, patients received ENB-0040, a bone-targeted, recombinant, human tissue-nonspecific isozyme of alkaline phosphatase that is lacking in this disease. Rickets healed, and developmental milestones and pulmonary function improved.

Kisspeptin and neurokinin B stimulate gonadotropin-releasing hormone. The authors describe an inactivating mutation in the human kisspeptin gene KISS1 leading to failure of pubertal progression.

This trial assessed alum-formulated glutamic acid decarboxylase, the 65-kD isoform (GAD65), a major autoantigen in type 1 diabetes. In patients with recent-onset disease; the compound did not significantly alter the loss of C peptide or improve clinical outcomes.

On whole-exome sequencing, a child with clinical hypothyroidism but borderline-abnormal thyroid hormone levels was found to have a heterozygous nonsense mutation in THRα, encoding a mutant protein inhibiting wild-type receptor action in a dominant negative manner.

The authors describe a germ-line mutation in the gene for PRKAR1A in three unrelated patients with acrodysostosis and resistance to multiple hormones. The mutated protein subunit impairs the response of protein kinase A to cyclic-AMP stimulation.

Perilipin, the most abundant adipocyte-specific lipid-droplet coat protein, is required for optimal lipid incorporation and release from the droplet. The authors identified mutations in the perilipin gene in families with partial lipodystrophy, severe dyslipidemia, and insulin-resistant diabetes.

The authors hypothesized that mutations in genes involved in idiopathic hypogonadotropic hypogonadism would be associated with functional hypothalamic amenorrhea, a reversible disorder commonly triggered by stress. Variants in such genes were detected in patients with hypothalamic amenorrhea.

In a family with high HDL, a genetic mutation was identified. In addition to higher HDL levels, carriers had reduced cholesterol efflux from macrophages, impaired platelet function, and attenuated adrenal steroidogenesis. No significant difference was seen in the carotid artery intima–media thickness.

Gigantism results from the presence of a growth hormone–secreting pituitary adenoma before epiphyseal fusion. The authors identified a mutation in a gene extracted from the teeth of an 18th-century giant and from contemporary Northern Irish families with gigantism, acromegaly, or prolactinomas.