Endocrine Abstracts

Non ketotic hyperglycinaemia (NKH)is due to a mutation in the glycine cleavage enzyme system leading to accumulation of glycine in the body especially in the spinal cord and brain. Patients typically present with neurological problems. Some NKH symptoms involve the inhibitory strychnine-sensitive glycine receptors, whereas the pathogenesis of seizures involves the excitatory strychnine-insensitive glycine receptors belonging to the N-methyl-D-aspartate (NMDA) receptor complex. Onset of puberty is marked by increase in pulsatile secretion of gonadotropin releasing hormone (GnRH). A previous report of an 11-month-old-girl with NKH and precocious puberty which regressed with anti-convulsive treatment with gamma-aminobutyric acid (GABA) agonists led to the hypothesis that excessive stimulation of the NMDA receptors linked to the Gonadotropin hormone-releasing hormone (GnRH) neurons by glycine led to the occurrence of precocious puberty in the child. This hypothesis is supported by in vitro studies in 15-day-old male rats which showed that glycine concentrations of 1-10 micromol/l increased the pulse frequency of GnRH secretion. We report another case of a 5-year-old girl with NKH presenting with precocious puberty providing more evidence of association of excessive accumulation of glycine and precocious puberty.

Case report: 5-year-old girl presented with new onset breast enlargement which was progressively getting bigger over the last 5 months. She had a background of NKH, global developmental delay (GDD), cortical visual impairment and Intractable epilepsy which were diagnosed in neonatal period. She was born at Term with Birth weight 2.8 kg. On examination she has obvious features of GDD. Pubertal examination showed breast enlargement stage 2 with no pubic hair, axillary or menarche. All other systemic examinations are unremarkable. Investigations showed that the luteinising Hormone (LH) rose from 1nmol/l to a peak of 32nmol/l and follicle stimulating hormone (FSH) rose from 4nmol/l to peak of 47nmol/l following GnRH stimulation test. Transabdominal pelvis ultrasound showed normal anteverted uterus with endometrium thickness 2. 3mm. The ovaries were not visualised. An incidental haematocolpos was present. MRI scan brain showed white matter loss with thinning of corpus callosum, asymmetrical atrophy, ventriculomegaly and central hypoplasia.

Conclusion: This case adds further evidence to association between excessive glycine and development of precocious puberty.