Rare Inborn Errors of Metabolism in Children in Latvia. Summary of the Doctoral Thesis

Abstract

Inborn errors of metabolism (IEM) or inherited metabolic diseases comprise a large class of genetic diseases involving disorders of metabolism. In most of the disorders, problems arise due to accumulation of substances which are toxic and it can cause acute or chronic intoxication, hypoglycaemia, or other metabolic disturbances. Clinical presentation in most cases are unspecific and in the neonatal period or during infancy could be misdiagnosed as manifestation of sepsis, birth trauma, encephalitis, sudden death syndrome or other disease. IEM individually are rare but collectively are common, and numbers of them are rising as there are improved diagnostic techniques. Data from literature suggest that risk for baby to be born with any of IEM is one in 500 newborns. It means, that in Latvia every year about 40 newborns are born with any IEM (presume that each year in Latvia there are ~20 000 newborns). There are known precise frequency for two inborn errors of metabolism in Latvia – phenylketonuria and congenital hypothyroidism due to newborn screening, which allows to diagnose precisely and to start treatment as early as possible. Those disorders, which are not included in newborn screening are more difficult to diagnose due to clinical variety. The aim of the study was to evaluate situation in Latvia in field of inborn errors of metabolism in childhood that could be detectable by selective screening. To reach this aim from 4600 patients, that were sent to Children’s University Hospital Medical Genetics Clinic during 1997 and 2010 years with unclear possible genetic pathology, later after examination, excluding chromosomal, neuromuscular and other syndromic cases, 2500 patients were sent to selective screening for IVS and out of them 108 patients had confirmed diagnose of rare inborn error of metabolism. Eighteen diseases were first time found in Latvia. The clinical and laboratory data were compared with data from other countries, calculated the prevalence of diagnosed IEM in Latvia and evaluated the problems in the diagnostic of rare inborn errors of metabolism in the state. There were worked out indications for further investigations in Medical Genetics’ clinic for patients with possible IEM. There were prepared information for doctors and medical professionals in Latvia about clinical signs and therapy during hyperamonemia and management of long-chain hydroxyacyl-CoA dehydrogenase deficiency patients in acute metabolic crisis. There were proposed actions for improving the diagnosis of rare IEM in Latvia.