Niemann-Pick disease

Niemann-Pick disease is a rare familial disorder inherited in an autosomal recessive manner and occurs primarily in Jews. The disease is caused by a deficiency of the enzyme sphingomyelinase in the lysosomes of cells of the reticuloendothelial system, which leads to the accumulation of sphingomyelin in the lysosomes. The liver and spleen are predominantly affected.

The inheritance pattern of Niemann-Pick disease is autosomal recessive, and this type of sphingolipidosis appears to be most common among Ashkenazi Jews; there are 2 types, A and B. Niemann-Pick disease type C is an unrelated enzyme defect in which there is an abnormal accumulation of cholesterol.

The cell has a characteristic appearance: pale, oval or round, 20-40 µm in diameter. In the unfixed state, granules are visible in it; when fixed with lipid solvents, the granules dissolve, thereby giving the cell a vacuolated and foamy appearance. Usually there are only one or two nuclei. When examined by an electron microscope, lysosomes are visible as lamellar myelin-like formations. They contain abnormal lipids.

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Symptoms of Niemann-Pick disease

Niemann-Pick disease type A (acute neuronopathic form) occurs in children who die before reaching 2 years of age. The disease begins in the first 3 months of life and is characterized by anorexia, decreased body weight, and growth retardation. The liver and spleen are enlarged, the skin becomes waxy and acquires a yellow-brown color on exposed parts of the body. The superficial lymph nodes are enlarged. Infiltrates occur in the lungs. Blindness, deafness, and mental disorders are noted.

Cherry-red spots are detected on the fundus, which appear as a result of retinal degeneration in the macula area.

Peripheral blood analysis reveals microcytic anemia, and in later stages Niemann-Pick foam cells may be detected.

The disease may first manifest itself as intermittent cholestatic jaundice of the newborn. As the child develops, neurological disorders appear.

Niemann-Pick disease type B (chronic form without nervous system involvement) presents with neonatal cholestasis, which resolves spontaneously. Cirrhosis develops gradually and may lead to portal hypertension, ascites, and liver failure. Cases of successful liver transplantation due to liver failure have been described. Although no signs of lipid deposition in the liver were detected during 10-month follow-up, a longer period is required to evaluate the outcome in terms of metabolic disorders.

Sea green histiocyte syndrome

A similar condition of Niemann-Pick disease is manifested by the presence of histiocytes in the bone marrow and reticuloendothelial cells of the liver, which acquire a sea-green color when stained with Wright or Giemsa. The cells contain deposits of phosphosphingolipids and glucosphingolipids. An increase in the size of the liver and spleen is noted. The prognosis of the disease is usually favorable, although cases of thrombocytopenia and cirrhosis of the liver have been described in these patients. Perhaps this condition is one of the variants of Niemann-Pick disease in adults.

Dementia in Pick's disease

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ICD-10 code

F02.0. Dementia in Pick's disease (G31.0+).

A progressive dementia of the neurodegenerative type, beginning in middle age (usually between 50 and 60 years), which is based on selective atrophy of the frontal and temporal lobes with a specific clinical picture: predominant frontal symptoms with euphoria, a gross change in the social stereotype of behavior (loss of a sense of distance, tact, moral principles; detection of disinhibition of lower drives), early gross violations of criticism in combination with progressive dementia. Speech disorders are also characteristic (stereotypies, impoverishment of speech, a decrease in speech activity to speech aspontaneity, amnestic and sensory aphasia).

For diagnosis, the clinical picture of frontal dementia is important - the early detection of prevailing frontal symptoms with euphoria, a gross change in the social stereotype of behavior in combination with progressive dementia, while the "instrumental" functions of the intellect (memory, orientation, etc.), automated forms of mental activity are impaired to a lesser extent.

As dementia progresses, focal cortical disorders, primarily speech disorders, take an increasingly important place in the disease picture: speech stereotypes ("standing turns"), echolalia, gradual vocabulary, semantic, grammatical impoverishment of speech, decreased speech activity to complete speech aspontaneity, amnestic and sensory aphasia. Inactivity, indifference, aspontaneity increase; in some patients (with predominant damage to the basal cortex) - euphoria, disinhibition of lower drives, loss of criticism, gross disturbances of conceptual thinking (pseudoparalytic syndrome).

Psychosis is not typical for patients with Pick's dementia.

Neurological disorders in patients are manifested by Parkinson-like syndrome, paroxysmal muscular atonia without loss of consciousness. For the recognition of Pick's dementia, the results of neuropsychotic examination are important: the presence of signs of aphasia (sensory, amnestic speech stereotypes, changes in speech activity, specific writing disorders (the same stereotypes, impoverishment, etc.), aspontaneity. At the initial stages of the disease, the disorders according to the results of neuropsychological examination are of little specificity. The results of neurophysiological examination are equally of little specificity for the diagnosis of Pick's dementia: a general decrease in the bioelectrical activity of the brain can be detected.

Pick's dementia should be differentiated from other types of dementia - this problem is relevant in the early stages of the disease.

Patients require care and supervision at the earliest stages of dementia due to severe behavioral disorders and emotional-volitional disorders at the onset of the disease. Treatment of productive psychopathological disorders is carried out according to the standards for treating the corresponding syndromes in elderly patients. Very careful use of neuroleptic drugs is indicated. It is necessary to work with the patient's family members, psychological support for people caring for the patient, due to the severe behavioral disorders characteristic of patients, requiring great efforts from the immediate environment.

The prognosis for the disease is unfavorable.

Diagnosis of Niemann-Pick disease

Diagnosis is by bone marrow aspiration, which reveals characteristic Niemann-Pick cells, or by decreased levels of sphingomyelinase in white blood cells. Both types are usually suspected based on history and examination findings, the most prominent of which is hepatosplenomegaly. Diagnosis can be confirmed by white blood cell sphingomyelinase testing and made prenatally using amniocentesis or chorionic villus sampling.

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Treatment of Niemann-Pick disease

Treatment of Pick's dementia is ineffective. Bone marrow transplantation has been performed in patients with early manifestations of severe liver damage; preliminary results have been promising. Decreases in sphingomyelin content in the liver, spleen, and bone marrow have been noted.