Early Presentation of Hyperinsulinism/Hyperammonemia Syndrome in Three Serbian Patients
Adrijan Sarajlija1, Tatjana Milenkovic2, Maja Djordjevic3, Katarina Mitrovic2, Sladjana Todorovic2, Bozica Kecman2, Khalid Hussain41Mother and Child Health Care Institute of Serbia “Dr Vukan Cupic”, Department of Metabolism and Clinical Genetics, Belgrade, Serbia2Mother And Child Health Care Institute Of Serbia “Dr Vukan Cupic”, Department Of Endocrinology, Belgrade, Serbia
3University of Belgrade Faculty of Medicine, Belgrade, Serbia
4University College London, Institute of Child Health, London, United Kingdom
Hyperinsulinism/hyperammonemia (HI/HA) syndrome is considered as the second most common type of hereditary HI. Correlation of genotype and phenotype in HI/HA syndrome has been described in several studies. We present three Serbian patients with HI/HA syndrome with emphasis on a possible correlation between genotype and clinical manifestations. Patient 1 was heterozygous for a de novo mutation p.S445L in the GLUD1 gene, while patients 2 and 3 (son and mother) both carry the p.R221C mutation. Early onset of hypoglycaemia with generalized seizures was recorded in infancy in all three patients. The two male patients had mild developmental delay, while the female patient presented with epilepsy. Analysis of Serbian patients with HI/HA syndrome confirms the association of p.S445L and p.R221C mutations with hypoglycaemic seizures noted within the first three months of life and with subsequent risk for cognitive impairment and/or epilepsy.
Keywords: Hyperinsulinism/hyperammonemia syndrome,genotype,phenotypeManuscript Language: English
