Pyruvate dehydrogenase complex deficiency with multiple minor anomalies

Abstract

Pyruvate dehydrogenase complex (PDHC) deficiency is known to cause congenital lactic acidosis. The case of a 9-month-old female infant with PDHC deficiency caused by a mutation in exon II of the pyruvate dehydrogenase (PDH) EIa gene is described. Her facial features were as follows: frontal bossing, upslanting palpebral fissures, a short upturned nose, a long philtrum and low set ears. These anomalies are characteristic not only of a malformation syndrome or chromosomal aberration, but also of PDHC deficiency. Because PDHC deficiency requires early treatment, metabolic disorders should be kept in mind in a patient with dysmorphic features. Further, she had multiple minor anomalies including bilateral inguinal herniae, an umbilical hernia and small hands and feet, which have not been described in previous reports.

Agenesis of the Corpus Callosum and Skeletal Deformities in Two Unrelated Patients: Analysis via MRI and Radiography

“…It has been suggested that there is a characteristic dysmorphic appearance associated with PDH deficiency, with a narrow head, frontal bossing, wide nasal bridge, long philtrum, and flared nostrils, but this is not seen in all cases and is not specific to the disease. Other congenital malformations such as simian creases, short neck, slight shortening of the limbs, flexion contractures, pes cavus, talipes, ventricular septal defects, and hydronephrosis have been described in few cases [17]. …”

Mitochondrial Factors and VACTERL Association-Related Congenital Malformations

“…First, embryogenesis is an energy-dependent process, and ATP availability is necessary for normal tissue development and organization [Stone and Biesecker, 1997;von Kleist-Retzow et al, 2003]. Animal models show that the period of embryogenesis is particularly vulnerable to mitochondrial dysfunction due to high energy demands as well as related results of aberrant mitochondrial function (see below) [Saijo et al, 1997;Li et al, 2000;Johnson et al, 2001;Dumollard et al, 2007]. Thus, a lack of necessary energy (e.g.…”

“…Thus, a lack of necessary energy (e.g. due to respiratory chain disease or mutations of pyruvate dehydrogenase-, cytochrome c-, or dihydrolipoamide dehydrogenase-encoding genes) may be detrimental to the developing embryo and lead to congenital anomalies [Saijo et al, 1997;Li et al, 2000;Johnson et al, 2001].…”

“…Dysmorphic facial features observed in conjunction with CNS malformations have been described as bearing some resemblance to fetal alcohol syndrome, which can include a long philtrum, epicanthal folds and a short nose with anteverted nares as well as additional features such as frontal bossing and upslanting palpebral fissures [Saijo et al, 1997;Cormier-Daire et al, 1996;Nissenkorn et al, 2001;Brown, 2005;Shih and Mandell, 2006]. In individuals with mitochondrial dysfunction, Cormier-Daire et al [1996] reported craniofacial anomalies, including round face, high forehead, flat philtrum, epicanthal folds, low-set ears, short neck, and ear dysplasia suggestive of the features seen in individuals with CHARGE syndrome as well as the structural malformations described above affecting the limbs, gastrointestinal, genitourinary, and cardiac systems [CormierDaire et al, 1996].…”

“…In individuals with mitochondrial dysfunction, Cormier-Daire et al [1996] reported craniofacial anomalies, including round face, high forehead, flat philtrum, epicanthal folds, low-set ears, short neck, and ear dysplasia suggestive of the features seen in individuals with CHARGE syndrome as well as the structural malformations described above affecting the limbs, gastrointestinal, genitourinary, and cardiac systems [CormierDaire et al, 1996]. Additional anomalies reported in individuals with IEM include genitourinary anomalies, inguinal and umbilical hernia, and brachydactyly as well as a spectrum of end-organ damage affecting multiple tissues (including the brain, liver and heart) [Goodman et al, 1983;Cormier-Daire et al, 1996;Saijo at al., 1997;Li et al, 2000;Johnson et al, 2001;Nissenkorn et al, 2001;Rudolph et al, 2002;De Meirleir, 2005;Shih and Mandell, 2006;Wajner and Goodman, 2011].…”