1.
Disorders of fatty acid oxidation and autosomal recessive polycystic kidney disease-different clinical entities and comparable perinatal renal abnormalities.
Hackl, A, Mehler, K, Gottschalk, I, Vierzig, A, Eydam, M, Hauke, J, Beck, BB, Liebau, MC, Ensenauer, R, Weber, LT, et al
Pediatric nephrology (Berlin, Germany). 2017;(5):791-800
Abstract
BACKGROUND Differential diagnosis of prenatally detected hyperechogenic and enlarged kidneys can be challenging as there is a broad phenotypic overlap between several rare genetic and non-genetic disorders. Metabolic diseases are among the rarest underlying disorders, but they demand particular attention as their prognosis and postnatal management differ from those of other diseases. METHODS We report two cases of cystic, hyperechogenic and enlarged kidneys detected on prenatal ultrasound images, resulting in the suspected diagnosis of autosomal recessive polycystic kidney disease (ARPKD). Postnatal clinical course and work-up, however, revealed early, neonatal forms of disorders of fatty acid oxidation (DFAO) in both cases, namely, glutaric acidemia type II, based on identification of the novel, homozygous splice-site mutation c.1117-2A > G in the ETFDH gene, in one case and carnitine palmitoyltransferase II deficiency in the other case. RESULTS Review of pre- and postnatal sonographic findings resulted in the identification of some important differences that might help to differentiate DFAO from ARPKD. In DFAO, kidneys are enlarged to a milder degree than in ARPKD, and the cysts are located ubiquitously, including also in the cortex and the subcapsular area. Interestingly, recent studies have pointed to a switch in metabolic homeostasis, referred to as the Warburg effect (aerobic glycolysis), as one of the underlying mechanisms of cell proliferation and cyst formation in cystic kidney disease. DFAO are characterized by the inhibition of oxidative phosphorylation, resulting in aerobic glycolysis, and thus they do resemble the Warburg effect. We therefore speculate that this inhibition might be one of the pathomechanisms of renal hyperproliferation and cyst formation in DFAO analogous to the reported findings in ARPKD. CONCLUSIONS Neonatal forms of DFAO can be differentially diagnosed in neonates with cystic or hyperechogenic kidneys and necessitate immediate biochemical work-up to provide early metabolic management.
2.
[Mitochondrial beta-oxidation defects].
Woldseth, B, Rootwelt, T
Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke. 2006;(6):756-9
Abstract
BACKGROUND Mitochondrial beta-oxidation of fatty acids is an important source of energy for the cells, especially during fasting. Since 1973 several inherited defects in beta-oxidation have been described. Defects in mitochondrial beta-oxidation are one of the largest groups of inborn errors of metabolism. MATERIAL AND METHODS This review article is based on the experience of the authors and on literature studies. The authors' experience is from laboratory diagnostics and clinical experience in the departments of medical biochemistry and peadiatrics at our hospital. RESULTS AND INTERPRETATION Beta-oxidation defects are potentially fatal disorders. Symptoms are usually seen during fasting, e.g. during childhood infections. Organs which preferably oxidize fatty acids or ketone bodies are especially vulnerable. Often, but not always, the patients have hypoketotic hypoglycaemia. In addition one can see affection of the liver, heart, muscular and nervous systems. The diseases can manifest both in childhood and adulthood and are often less severe in adulthood. The main principles of symptomatic treatment are avoidance of fasting and regular intake of a low-fat, high-carbohydrate diet. The diagnosis can be difficult to establish, especially in asymptomatic phases.
3.
Role of carnitine and fatty acid oxidation and its defects in infantile epilepsy.
Tein, I
Journal of child neurology. 2002;:3S57-82; discussion 3S82-3
Abstract
Defects in fatty acid oxidation are a source of major morbidity and are potentially rapidly fatal. Fatty acid oxidation defects encompass a spectrum of clinical disorders, including recurrent hypoglycemic, hypoketotic encephalopathy or Reye-like syndrome in infancy with secondary seizures and potential developmental delay, progressive lipid storage myopathy, recurrent myoglobinuria, neuropathy, and progressive cardiomyopathy. As all of the known conditions are inherited as autosomal recessive diseases, there is often a family history of sudden infant death syndrome in siblings. Early recognition and prompt initiation of therapy and the institution of preventive measures may be life saving and significantly decrease long-term morbidity, particularly with respect to central nervous system sequelae. Seizures may be the result of cerebral bioenergetic failure associated with acute episodes of hypoglycemic, hypoketotic encephalopathy, or hypoxic-ischemic encephalopathy in the context of cardiac arrhythmias and/or cardiomyopathy. This review provides an overview of the fatty acid oxidation pathway and the central role of carnitine, as well as a discussion of normal fasting adaptation and the critical metabolic adaptations that occur at birth. The increased vulnerability of infants and young children to fasting and defective fatty acid oxidation is discussed in the context of the heightened bioenergetic demands of the developing brain. Clinical and laboratory features of specific genetic defects in fatty acid oxidation, approaches to diagnosis, and current treatment methodologies are described. Indications for carnitine supplementation in childhood epilepsy are also discussed.