See also Chapter 105.4 . Overview of Mitochondrial Disease Mitochondrial diseases are multisystemic energy failure states with extensive clinical and genetic heterogeneity. Their common basis is best understood through recognition that mitochondria function as biologic “fuel cells” or “batteries,” producing…
Carbohydrate synthesis and degradation provide the energy required for most metabolic processes. The important carbohydrates include 3 monosaccharides—glucose, galactose, and fructose—and a polysaccharide, glycogen. Fig. 105.1 shows the relevant biochemical pathways of these carbohydrates. Glucose is the principal substrate of…
Disorders of Mitochondrial Fatty Acid β-Oxidation Charles A. Stanley Michael J. Bennett Keywords fatty acid oxidation defects carnitine cycle newborn screening hypoglycemia medium-chain acyl-CoA dehydrogenase deficiency liver disease cardiomyopathy rhabdomyolysis fasting intolerance mitochondrial metabolism Reye syndrome Mitochondrial β-oxidation of fatty acids is…
Phenylalanine Oleg A. Shchelochkov Charles P. Venditti Keywords phenylalanine phenylketonuria PKU hyperphenylalaninemia phenylalanine hydroxylase tetrahydrobiopterin BH4 Phenylalanine is an essential amino acid. Dietary phenylalanine not utilized for protein synthesis is normally degraded by way of the tyrosine pathway ( Fig. 103.1 ).…
Many childhood conditions are caused by single-gene mutations that encode specific proteins. These mutations can change primary protein structure or the amount of protein synthesized. The function of a protein, whether it is an enzyme, receptor, transport vehicle, membrane component,…
Rare and novel disorders often present in childhood and represent a diagnostic challenge that can be addressed using advanced genetic techniques. In the United States, rare disorders are defined as those affecting <200,000 people (about 1 in 1,500 persons), but…
Pediatricians are asked to consider the possibility that certain conditions involve epigenetic mechanisms. The assumption is that epigenetic processes, generally defined as regulatory control of gene expression, are capable of overriding information encoded in the DNA sequence to increase or…
Common pediatric diseases are usually multifactorial. The combination of many genes and environmental factors contribute to a complex sequence of events leading to disease. The complexity of the combination of contributing factors increases the challenge of finding genetic variants that…
Clinical cytogenetics is the study of chromosomes: their structure, function, inheritance, and abnormalities. Chromosome abnormalities are very common and occur in approximately 1–2% of live births, 5% of stillbirths, and 50% of early fetal losses in the 1st trimester of…
Family History and Pedigree Notation The family history remains the most important screening tool for pediatricians in identifying a patient's risk for developing a wide range of diseases, from multifactorial conditions such as diabetes and attention-deficit/hyperactivity disorder, to single-gene disorders…