Visceral Steatosis, Congenital

Clinical Features

Peremans et al. (1966) described a sibship of 14 children, offspring of first cousins once removed, among whom 5 children showed progressive muscular hypotonia, lethargy, coma, and death in the first days of life. A sixth child was found to have hypocalcemia and hypoglycemia. At autopsy, the heart, liver, and kidneys were grossly very pale; histologically, these organs and others showed loading of parenchymal cells with sudanophilic material. Autopsy in 2 of the other infants also showed pallor of viscera. The relationship to the condition described by Utian et al. (1964) and Reye et al. (1963) was unclear.

Satran et al. (1969) described 2 brothers and a sister who died at ages 4 days, 19 days, and 12 weeks of fatty liver disease marked by a severe hemorrhagic disorder. They suggested that the disorder reported by Peremans et al. (1966) may be the same.

Wadlington and Riley (1973) described a family in which 5 male sibs died in the first 2 weeks of life after an illness characterized by jaundice and kernicterus. Liver tissue obtained at autopsy in 1 showed a striking increase in total lipids and fatty acids.

Suprun and Freundlich (1981) reported 3 affected sibs who died early, 2 of them in the first days of life and 1 at the age of 7 months, with heart failure. Autopsy in all 3 demonstrated diffuse, intense fatty degeneration of the liver and myocardium, with focal renal tubular epithelial involvement. The parents were unrelated.

Chesney et al. (1983) discussed the case of a 3.5-month-old girl who developed hypoglycemic seizures. The mother was diabetic. No relevant family history was given. At autopsy the liver was pale and yellow. The serum was milky with chylomicrons and a high pre-beta peak and high peak of high-density lipoprotein on electrophoresis. The liver showed a concentration of fatty acids about 15 times normal and high triglycerides. Microscopically, the liver showed extreme fatty change. After a discussion of causes of fatty metamorphosis of the liver, it was concluded that the infant presumably lacked one of the mechanisms by which triglycerides formed in hepatocytes are excreted into the circulation. A disturbance of lipoprotein metabolism is suggested by the presence of chylomicrons despite lack of fat intake.

Animal Model

Using adenosine kinase (ADK; 102750)-targeted embryonic stem cells to generate Adk-deficient mice, Boison et al. (2002) pursued the hypothesis that a deficit in adenosine-dependent metabolism is a causative factor for the development of microvesicular hepatic steatosis. Homozygous Adk -/- mice developed normally during embryogenesis. However, within 4 days after birth they displayed microvesicular hepatic steatosis and died within 14 days with fatty liver. Adenine nucleotides were decreased and S-adenosylhomocysteine, a potent inhibitor of transmethylation reactions, was increased in the mutant liver. Thus, a deficiency of adenosine metabolism was identified as a powerful contributor to the development of neonatal hepatic steatosis, providing a model for the rapid development of postnatally lethal fatty liver.

History

In the sibship reported by Rasanen et al. (1971), a female sib died at 19 months and a male sib at 56 hours. Simila et al. (1984) provided follow-up on the kindred reported by Rasanen et al. (1971). It turned out that these patients with hepatic steatosis had nonketotic C6-C10-dicarboxylic aciduria with episodes of a Reye-like syndrome and profound hypoglycemia. The conclusion was based on findings in a third affected sib still living, aged 7 at the time of report. After a respiratory infection at 13 months she became semicomatose, developing hepatomegaly and mild hypoglycemia. A similar but less severe Reye-syndrome-like episode occurred at 6 years. Psychomotor development was normal. Thus, this appears to be the disorder discussed in entry 201450.