The positive regulatory (PR) domain containing 13 (PRDM13) putative chromatin modifier and transcriptional regulator functions downstream of the transcription factor PTF1A, which controls GABAergic fate in the spinal cord and neurogenesis in the hypothalamus. Here, we report a recessive syndrome associated with PRDM13 mutation. Patients exhibited intellectual disability, ataxia with cerebellar hypoplasia, scoliosis, and delayed puberty with congenital hypogonadotropic hypogonadism (CHH). Expression studies revealed Prdm13/PRDM13 transcripts in the developing hypothalamus and cerebellum in mouse and human. An analysis of hypothalamus and cerebellum development in mice homozygous for a Prdm13 mutant allele revealed a significant reduction in the number of Kisspeptin (Kiss1) neurons in the hypothalamus and PAX2 + progenitors emerging from the cerebellar ventricular zone. The latter was accompanied by ectopic expression of the glutamatergic lineage marker TLX3. Prdm13 -deficient mice displayed cerebellar hypoplasia and normal gonadal structure, but delayed pubertal onset. Together, these findings identify PRDM13 as a critical regulator of GABAergic cell fate in the cerebellum and of hypothalamic kisspeptin neuron development, providing a mechanistic explanation for the cooccurrence of CHH and cerebellar hypoplasia in this syndrome. To our knowledge, this is the first evidence linking disrupted PRDM13-mediated regulation of Kiss1 neurons to CHH in humans.

Aim This literature review seeks to establish whether suffi cient evidence showing an additional benefi t of continuous glucose monitoring (CGM) on diabetes outcomes compared to intermittent self monitoring of blood glucose (SMBG) alone, in type 1 diabetic children, is available. Methods Electronic databases were searched using a specifi c search strategy. Hand searches of relevant journals and of reference lists of relevant articles were carried out. Studies eligible for inclusion were published randomised controlled trials (RCTs) investigating the effi cacy of CGMS as an adjunct to SMBG in children/adolescents with T1DM, compared to intermittent SMBG alone. Included studies were evaluated for methodological quality. Data was extracted on study design and relevant outcomes. Results The search yielded 5 RCTs comparing retrospective CGMS with SMBG involving 137 participants aged 2-19 years. The search also yielded another 8 RCTs and 2 follow on studies of 2 of the RCTs which compared real time CGMS with SMBG, involving 554 participants aged 1-18 years. Three out of 5 studies of retrospective CGMS did not fi nd any additional benefi t of CGMS on HbA1c. In all the studies of real time CGMS a correlation between frequency of CGMS use and decrease in HbA1c was found, with regular CGM use being associated with a decrease in HbA1c of between 0.5% to 1.0%. Some of the trials confi rmed a decrease in glycaemic variability, a decreased exposure to hypoglycaemia and of time with glucose values out of range. Satisfaction with CGM was high but in spite of this most children chose not to use sensors regularly implying an increased treatment burden.

In Malta, the number of children/adolescents with T1DM has been rising at a faster rate than expected, and a distinct shift to younger age at onset has been observed. DKA rate at presentation is still high in Maltese children.

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Background: We report the case of a female infant with hypoparathyroidism due to an activating mutation in the calcium-sensing receptor gene. Case Report: The child presented in the neonatal period with clinical seizures associated with severe hypocalcaemia, hyperphosphataemia, low parathyroid hormone levels and elevated urine calcium:creatinine ratios. She required intravenous calcium and phenobarbitone initially, and then oral 1-alfacalcidol (1-AC) and phenobarbitone were started. The patient had intractable hypocalcaemia in the first 5 months of life despite escalating doses of 1-AC. When the phenobarbitone was stopped at 5 months of age she was admitted soon after with symptomatic hypercalcaemia. We postulate that the phenobarbitone increased the metabolism of 1-AC and thus she needed large doses of 1-AC to treat hypocalcaemia until the phenobarbitone was stopped. Her parents had no biochemical abnormalities on testing. Results: Molecular genetic analysis confirmed that our patient had a de novo missense variant, c.682G>A (p.Glu228Lys) in exon 4 of the calcium-sensing receptor. Conclusion: This case report highlights the importance that clinicians caring for children on vitamin D and its analogues are aware of the interaction with phenobarbitone, which can result in symptomatic hypocalcaemia. 1-AC should be stored at 2-8°C, otherwise it will be rendered inactive.