Severe Hypoglycemia and Liver Disease with Excellent Prognosis: Looking Deep into the Genes
2Department of Molecular and Medical Genetics, Tbilisi State Medical University, Tbilisi, Georgia
3Department of Pediatrics, Children’s Hospital Medical Center,university of Bonn, Bonn, Germany
Background: Pediatric hypoglycemia is a heterogeneous disorder with various etiologies, including inborn errors of metabolism (IEM). If untreated it can cause severe complications and even death. Identification of the etiology is crucial for proper management and outcome.
Case report: We describe a 5y boy with recurrent episodes of hypoglycemia shortly after birth. The episodes occurred every 1-2 month and were mostly triggered by infections, fever or diarrhea, with or without fasting at any time of the day. The child had normal cognitive and motor development. During episodes main complains were fatigue and unconsciousness. Blood glucose levels were between 24-55 mg%, lactate and ketones were high, liver transaminases were markedly elevated, but ammonia, CPK, direct and total bilirubin, INR, pH, insulin, cortisol, plasma amino acids and urine organic acids were normal. No history of seizures. Glycogen storage diseases were excluded by a normal liver biopsy.
Methods: A gene panel of lysosomal and glycogen storage diseases (51 genes) revealed two heterozygous variants in POLG gene: c.156_158dupGCA (considered as pathogenic with population frequency of 0.3%) and c.803G>C (considered as benign with population frequency of 10%). Considering clinical heterogeneity of POLG-related disease Alper’s syndrome was suspected and MLPA of POLG gene was requested to look for another pathogenic variant, but without success. As a next step Whole Exon Screening trio was performed and homozygous pathogenic deletion encompassing exon 2 of the FBP1 gene was identified, causative for fructose-1,6-bisphosphatase deficiency. Parents were heterozygous carriers of the known variant.
Results: Currently the patient is on fructose restricted diet, avoiding fasting and taking starch. 2 years since the diagnosis he lives without hypoglycemic episodes.
Conclusion: Diagnosis of IEM should be suspected in any child with unclear hypoglycemia and liver disease. Early diagnosis improves management and outcome of the disease and even may be life-saving
Powered by Eventact EMS