One of the varieties of amaurotic idiocy, namely, its juvenile form, has been named an independent disease of Spielmeyer-Fogt disease. This nosology belongs to a group of genetically determined pathologies based on dysmetabolism of gangliosides with their cumulation in ganglion cells. Affinity with leptin is mediated, since lipid metabolism disorders are revealed in the development of the disease. What are the leading symptoms of Spielmeier-Vogt disease, diagnosis and possible correction, you will learn from the article.
- General information.
- Classification and symptoms.
- Prognosis and prevention.
Amaurotic idiocy was first described in the late 19th century by the American ophthalmologist W. Tay, who systematized materials on the study of patients’ ocular fundus. Later, his colleague, the neurologist B. Sachs, presented a clinical picture of the disease and concluded that the pathology was familial in nature. Thus, the most famous variant of amaurotic idiocy – Thea-Sachs disease – was discovered. Then two pediatricians working in the field of clinical neurology described other forms of the disease, which had a later onset. Among them was the juvenile variety or Spielmeier-Fogt disease.
Statistically, the prevalence of the pathology in the general population is 1 case per 500,000 population, among Jews – per 6,000 population. There are no gender shades in the pathological condition, no seasonality was detected.
The disease is familial in nature and at its core contains gene mutations that control metabolism in the body, and especially – fat metabolism. Inheritance is autosomal recessive with high penetrance of the defective gene. To transmit the juvenile form of amaurotic idiocy, the genes of both parents must be involved. In this case, the probability of giving birth to a sick child is 25%.
The mechanism of genetic mutation of the gene controlling the processes of catabolic breakdown of tissues with ganglioside cleavage is the most studied. Enzyme deficiency provokes their cumulation in the ganglion cells of the nervous system, brain, and retina. It is these structures that degrade in the first place.
And the basis of all – altered metabolism with deposition of lipids in the neurons of the brain and retina cells, much less – in the liver and spleen. Dismetabolic shifts are expressed in cumulation of lipid inclusions of different composition. The juvenile variant of the pathology is distinguished by the fact that instead of cholesterol and its low-density and high-density fractions there is protein cumulation. There is no cholesterol.
Macroscopically, the disease is manifested by increased brain volume, atrophy of occipital lobes, cerebellum, and degeneration of the visual tract. Microscopically, ganglion cells in the brain swell, the intracellular space is filled with lipoid inclusions, cell nuclei shrink, and the thigroid substance disintegrates. The same negative processes occur in retinal cells with a peak in the yellow spot area.
Classification and symptoms
There is no separate classification of the juvenile form, it itself is part of the gradation of amaurotic idiocy, which includes several variants of pathological changes with different debut, the nature of the course and the duration of life of patients.
According to this state of affairs, four kinds of idiocy are distinguished:
- Infantile or early childhood Tay-Sachs form – the most studied, with manifestation of symptoms in the first six months of life, rapidly progressing course and fatal outcome before the age of three.
- Jansky-Bilshovsky’s form or late childhood form with debut at the age of three to four years. It courses similarly to the early variety, but a little slower. Death occurs in six years at most.
- The juvenile form or Spielmeier-Fogt disease is symptomatic at 6 to 9 years of age and is characterized by relatively slow progression of the disease. Patients live to be 20 years old.
- The Kufs form or late variant of amaurotic idiocy manifests in puberty and older. Here the most favorable course is observed, and the fatal outcome occurs 15 years after the debut of the pathology.
In some cases, congenital amaurotic idiocy called the Norman-Wood form develops. Symptoms develop immediately after birth, the essence being a complete blockage of neuropsychological development. It is an extremely rare pathology.
The basis of the clinic is visual disturbances with a steadily progressive course combined with loss of intellect. Deafness, seizures, extrapyramidal disorders, ataxia of cerebellar genesis can be considered as concomitant pathology. The severity of the course correlates with the form of the disease. Juvenile is characterized by mild progression: intellect and motor function are destroyed only slightly, visual dysfunction is not fatal. Extrapyramidal disorders, cerebellar dysfunction are typical, deafness, epileptic seizures may develop, myxedematous obesity is often visualized. This is where the affiliation of the pathology with leptin manifests itself.
Since the main disorders in the juvenile form are visual, complications are considered frequent injuries to the child. Restriction of mobility provokes congestive pneumonia, seizure syndrome causes epilepsy. Bulbar syndrome provokes dysphagia, ingestion of fluid and food into the airways with the development of aspiration inflammation of the lungs.
A number of other complications are associated with fat accumulation in internal organs. Fat infiltration of the liver leads to liver failure, and fat in the myocardium leads to heart failure. Patients die from respiratory or cardiac failure, secondary infection, and multiple organ failure.
The juvenile form is characterized by a triad of symptoms: degradation of cognitive functions, a sharp decrease in visual acuity, and motor disorders. In addition, a number of investigations help to make the diagnosis:
- Testing of neurological status: sharp discrepancy between intelligence and age, spastic paresis, cerebellar dysfunction, hyperkinesias, muscular dystonia, autonomic-trophic disorders.
- Ophthalmologic disorders: lack of tracking reactions in newborns, decreased visual acuity in older patients, optic atrophy on both sides.
- Laboratory examination: lymphocytes with vacuoles, changes in lipid profile, leptin resistance, increased cholesterol, lipid metabolism enzymes.
- Brain MRI – moderate atrophy of cerebral neurons, thinning of the optic nerve.
- Brain tissue biopsy for cytology and histology with visualization of characteristic intracellular lipid inclusions, the color of which is used to judge the form of pathology.
- Genetic markers: family history, genealogical tree.
It is necessary to differentiate the disease from hereditary degeneration, dimetabolic processes, CNS degeneration.
There is no specific treatment today. Only symptomatic treatment is possible. For seizures – anticonvulsants, psychiatric disorders – psychotropics, neuroleptics, tranquilizers, sedatives. Some doctors talk about the effectiveness of blood transfusions, plasma. General restorative and vitamin therapy is used as a background. For the prevention of complications, meticulous care is needed. Great hopes are pinned on genetic engineering, but for now – that is in the future.
Prognosis and prevention
In Spielmeier-Fogt disease, the prognosis is unfavorable. Fatal outcome occurs no later than 20 years of age. Prophylaxis is to avoid close marriages. If parents already have one sick child, they are strongly advised not to have further children. If we are talking about pregnancy in a heterozygous couple, everything is solved by consulting a geneticist and examining the concentration of hexosaminidase-A in the amniotic fluid. Pregnancy is terminated only in case of a sharp decrease in the level of the enzyme.