MedGen

Pyruvate dehydrogenase deficiency is characterized by the buildup of a chemical called lactic acid in the body and a variety of neurological problems. Signs and symptoms of this condition usually first appear shortly after birth, and they can vary widely among affected individuals. The most common feature is a potentially life-threatening buildup of lactic acid (lactic acidosis), which can cause nausea, vomiting, severe breathing problems, and an abnormal heartbeat. People with pyruvate dehydrogenase deficiency usually have neurological problems as well. Most have delayed development of mental abilities and motor skills such as sitting and walking. Other neurological problems can include intellectual disability, seizures, weak muscle tone (hypotonia), poor coordination, and difficulty walking. Some affected individuals have abnormal brain structures, such as underdevelopment of the tissue connecting the left and right halves of the brain (corpus callosum), wasting away (atrophy) of the exterior part of the brain known as the cerebral cortex, or patches of damaged tissue (lesions) on some parts of the brain. Because of the severe health effects, many individuals with pyruvate dehydrogenase deficiency do not survive past childhood, although some may live into adolescence or adulthood. [from MedlinePlus Genetics]

An increased concentration of prostaglandin E2 in the blood. [from HPO]

Any brachydactyly type E in which the cause of the disease is a mutation in the PTHLH gene. [from MONDO]

Persistent patency of the ductus arteriosus, or patent ductus arteriosus (PDA), is the second most common congenital heart disease, affecting approximately 1 in 1,600 to 5,000 live births in the U.S. (Mitchell et al., 1971). In fetal life, the ductus arteriosus, a muscular artery, shunts blood from the pulmonary artery to the aorta, bypassing the lungs. Its abrupt closure at birth establishes the mature circulatory pattern and represents a dramatic example of vascular remodeling. Failure of this normal process results in persistent PDA, which left untreated can result in pulmonary hypertension and heart failure. Closure of the ductus is a complex process. Aspects of this process are regulated by oxygen tension and a decrease in levels of hormones such as prostaglandin E2. PDA occurring in preterm infants often closes spontaneously or in response to inhibitors of prostaglandin biosynthesis (Ramsay et al., 1987). Term PDA typically has not been regarded as a genetic disorder, because it most often occurs sporadically. Nonetheless, term PDA recurs among 5% of sibs of PDA cases (Polani and Campbell, 1960; Lamy et al., 1957), suggesting a genetic component to disease pathogenesis that has typically been presumed to be multifactorial. That single genes can influence this trait has been demonstrated by a mouse model of PDA resulting from disruption of the prostaglandin E2 receptor (Nguyen et al., 1997) and by rare syndromic forms of PDA such as Char syndrome (169100), an autosomal dominant disorder caused by mutations in the transcription factor TFAP2B (601601) (Mani et al., 2002). Genetic Heterogeneity of Patent Ductus Arteriosus Autosomal dominant forms of patent ductus arteriosus include PDA2 (617035), caused by mutation in the TFAP2B gene (601601) on chromosome 6p12, and PDA3 (617039), caused by mutation in the PRDM6 gene (616982) on chromosome 5q23. Hajj and Dagle (2012) reviewed the genetics of patent ductus arteriosus in both term and preterm infants, and discussed possible environmental risk factors as well as animal models of PDA. [from OMIM]