Case Report: Patient with POLG Mutation with the Clinical Picture of a Myocerebrohepatopathy Syndrome
Case Study: POLG-related disorders comprise a continuum of overlapping phenotypes. So far, childhood myocerebrohepatopathy spectrum (MCHS) has been described in only few patients. It presents in the first few months of life with developmental delay, lactic acidosis, and a myopathy with failure to thrive. Other findings can include liver failure, renal tubular acidosis, pancreatitis, cyclic vomiting, and hearing loss.
Case Report: Our patient was born after an uneventful pregnancy. She presented with respiratory problems after birth (CPAP- therapy necessary) and a bilateral hearing loss. During the first few weeks of life, she demonstrated a severe hypotonia and later on rapidly progressive failure to thrive. Frequent vomiting caused an escalation of therapy from nasogastral tube to gastrostomy tube, jejunal tube, and then total parenteral nutrition (TPN). With TPN, she started to grow and became more awake at times of less vomiting. She developed pathological liver function tests and pancreatitis. At the age 7 months severe hypoglycemia during infusion stop of less than 10 minutes was observed.
Diagnostics: Lactate was increased in urine and spinal fluid but not in blood. Muscle biopsy showed at electron-microscopic level small mitochondria with lipid inclusions and low glycogen. Sequencing of POLG showed a polymorphism (p.Glu1143Gly, maternal) and the following two most likely pathogenic mutations:
The first mutation has been described before in association with POLG-related disorders and has a very variable phenotype, the second mutation is located at a highly conserved site and has not been described before. The segregation of the parental origin of the mutations is in accordance with the pathogenicity.
Summary: We describe a patient with the clinical picture of myocerebrohepathopathy syndrome and compound heterozygous POLG mutations. The early manifestation of a multisystem disease with increased lactate made a mitochondrial dysfunction very likely. Sequencing of POLG should be encouraged early in infants with supposed mitochondrial disease.
Keywords: POLG, myocerebrohepatopathy syndrome.