Progressive sclerosing polyodystrophy of Alpers

Alpers' progressive sclerosing polydystrophy (OMIM 203700) was first described by BJ Alpers in 1931. The population frequency has not yet been established. It is inherited in an autosomal recessive manner. The localization of the gene has not been established.

The disease is based on a deficiency of energy metabolism enzymes - pyruvate decarboxylase, complexes 1, 3 and 4 of the respiratory chain or cytochromes. Pathogenesis is associated with the development of lactic acidosis due to disruption of cellular bioenergetic processes.

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Symptoms of Alpers' progressive sclerosing polydystrophy

Symptoms of the disease develop in early childhood - in the 1st-2nd year of life. The disease begins with seizures (partial or generalized) and myoclonus, resistant to anticonvulsant treatment. Subsequently, there is a delay in psychomotor and physical development, loss of previously acquired skills, muscle hypotonia, spastic paresis, increased tendon reflexes, ataxia. There are episodes of vomiting, lethargy, decreased vision and hearing. Hepatomegaly often develops, jaundice, cirrhosis of the liver, liver failure appear, which can lead to the death of children. The disease is progressive, at the age of 3-4 such patients die.

In addition to typical forms, there are acute neonatal and late forms of the disease. In the neonatal form, the course of the disease becomes severe immediately after birth. Microcephaly, intrauterine growth retardation and weight loss, chest deformation, limited joint mobility, micrognathia, convulsive syndrome, and difficulty swallowing are noted. In the late form, the first symptoms appear after 16-18 years of age.

Biochemical studies reveal increased levels of lactic and pyruvic acids, direct and indirect bilirubin; with late diagnosis, decreased levels of albumin, prothrombin, and hyperammonemia.

The EEG results reveal high-amplitude slow-wave activity and polyspikes.

According to MRI data, there is an increase in signal on T2 _images in the area of the cerebral cortex, occipital lobes and thalamus.

Morphological examination of brain tissue reveals generalized brain atrophy, spongy degeneration of gray matter, neuronal death, and astrocytosis. In the liver, fatty degeneration, bile duct proliferation, fibrosis or cirrhosis, hepatocyte necrosis, and abnormal mitochondria (by size and shape) are found. Muscle biopsies reveal accumulation of lipid substances and disruption of mitochondrial structure. The RRF phenomenon is rarely detected.