Psychiatry - O. K. Napreyenko 2001

Clinical Psychiatry
Intellectual Disability (Oligophrenia)

General characteristics

Intellectual disability is a group of conditions diverse in Etiology AND Pathogenesis that result from adverse factors during the prenatal period or early childhood (typically up to the age of 3), leading to psychological underdevelopment with a primary deficit in intellect, which partially or fully impairs social functioning. Over the past two decades, the term "intellectual disability" has replaced "oligophrenia," which was introduced by E. Kraepelin in 1915. Intellectual disability is characterized by global mental underdevelopment.

The primary feature is a marked reduction in The ability to formulate concepts, generalize, and engage in Abstract thinking. Intellectual disability affects the personality as a whole, often manifesting as speech underdevelopment, characteristic movements, and facial expressions. While such patients are able to perceive differences between objects and phenomena, they are incapable of establishing similarities between them. They fail to understand the figurative meaning of proverbs, sayings, and metaphors, and are unable to extract the main idea from a text they have read.

Weakness in abstract thinking impacts all cognitive processes; consequently, these patients find it difficult or impossible to learn arithmetic, solve problems, or correctly apply grammatical rules. Their capacity for analyzing and synthesizing information about objects and phenomena is impaired. Metaphorically speaking, these patients "see little when they look, and hear little when they listen." Their logical memory is significantly reduced compared to their mechanical memory, and they are generally unable to retell the content of what they have heard, seen, or read.

The delayed formation of cognitive Functions leads to speech underdevelopment, the degree of which corresponds to the severity of the intellectual impairment. In cases of profound intellectual decline, an individual may be unable to speak or comprehend spoken language, though intonations and gestures retain significant communicative value. The inability to think abstractly leads patients to rely on memorized clichés without understanding their meaning. Their vocabulary is typically limited (depending on the degree of intellectual impairment), and signs of speech underdevelopment are also manifested in pronunciation defects. The emotional sphere remains intact.

Taking into account temperament characteristics, intellectual disability is subdivided into torpid and erethic forms. Such patients lack initiative and, due to increased suggestibility, are easily influenced by both positive upbringing and negative external factors. In addition to underdevelopment of the mental sphere, pathology of other Organs and systems is frequently observed.

When assessing an individual's intellectual level, all available information regarding the intelligence quotient (IQ) should be utilized. IQ is determined using an adapted Wechsler scale, which assesses the degree of language development (vocabulary) as well as memory, attention, behavior, learning capacity, and other parameters. Standardized tests that account for local cultural specificities are also used to measure intellectual development.

Clinical Classification

According to ICD-10

F70 — Mild intellectual disability

F71 — Moderate intellectual disability

F72 — Severe intellectual disability

F73 — Profound intellectual disability

According to the traditional domestic classification, intellectual disabilities are divided into debility (mild intellectual disability), imbecility (moderate and severe), and idiocy (profound intellectual disability).

Patients with mild intellectual disability acquire speech with some delay and can use it in everyday life. Adaptive skills at the household level are also fairly well developed; they are capable of self-care (eating, washing, dressing, controlling physiological functions) and acquiring simple practical skills. However, they are unable to study in a regular school due to weaknesses in abstract and theoretical thinking, as well as delays in The formation of concepts, judgments, and semantic connections. Because this type of intellectual impairment affects the personality as a whole, a lack of capacity for self-assertion and self-awareness becomes evident already during school years. With appropriate pedagogical Methods, however, they can develop adequate adaptive skills and manual dexterity enabling them to perform low-skilled labor. Social limitations are most often caused by personal immaturity, along with emotional and volitional deficits. The intelligence quotient ranges between 50—69.

In moderate intellectual disability, speech develops slowly, and patients have difficulty fully understanding others. They struggle to master self-care skills, and the majority require supervision. They acquire only the basics of reading and writing, and their vocational skills are similarly limited. Social development may reach a level that enables them to establish contacts, communicate with others, and participate in elementary social activities. The intelligence quotient ranges from 35 to 49.

Severe intellectual disability is characterized by more pronounced motor impairments or other clinically significant organic stigmata. The intelligence quotient ranges from 20 to 34.

In profound intellectual disability, mobility is restricted, and patients are unable to control physiological functions. Speech is impoverished; vocabulary is either absent or limited to isolated words, though elementary non-verbal communication is possible. To use the phrasing: "They look and listen, but understand nothing." Patients require constant care. The intelligence quotient is below 20. Profound intellectual disability is frequently accompanied by severe somatic and neurological disorders.

Individuals with intellectual disability may exhibit the entire spectrum of mental disorders, but their prevalence is 3 to 4 times higher than in the general population.

The Diagnosis of intellectual disability should be based on the following key criteria: 1) global mental underdevelopment; 2) impairment of higher forms of cognitive activity (abstract thinking). Emotional and volitional disturbances accompanying the cognitive deficit can vary. Traditional classifications historically distinguished between torpid (apathetic) and "excitable" (morioid) forms of intellectual deficiency.

When diagnosing and prognosticating intellectual disability, it is essential to consider the dynamics of the disorders, which depend on compensation and reparation processes in the Central Nervous system. Traditionally, a distinction is made between positive dynamics—characterized by a steady improvement in the individual's adaptive capabilities—and negative dynamics, caused by decompensation during age-related crises and The impact of exogenous or psychogenic harmful factors. Manifestations of decompensation in intellectual disability can vary, ranging from deeper organic pathology to behavioral and drive disorders (vagrancy, sexual disinhibition, aggression, etc.). Negative dynamics may also present as psychoses featuring affective, psychomotor, and hallucinatory-paranoid phenomena. In such cases, these must be differentiated from process-based mental illnesses (progressive organic Brain damage, Epilepsy, Schizophrenia).

Classification of Specific Forms of Intellectual Disability

I. Hereditarily determined forms:

1) Chromosomal Disorders (Down syndrome, Turner syndrome, Triple X syndrome, Klinefelter syndrome, XYY syndrome);

2) Monogenic Disorders (phenylketonuria, histidinemia, galactosemia, fructosuria, amaurotic idiocy, Martin-Bell syndrome).

II. Intellectual disability of hereditary-exogenous etiology (microcephaly, cretinism).

III. Exogenously conditioned forms of intellectual disability (fetal alcohol fetopathy, intellectual disability due to immunogenetic incompatibility by Antigens or the Rh factor).

HEREDITARILY CONDITIONED FORMS OF INTELLECTUAL DISABILITY

Forms of intellectual disability caused by chromosomal disorders

Down syndrome was described in 1866 by J. L. Down, who suggested its hereditary nature. Its incidence is 1 per 700 newborns, and among patients with oligophrenia, it reaches 9–10%.

Etiology. Non-disjunction of the 21st pair of Chromosomes, which correlates with maternal age.

The following variants of Down syndrome are distinguished: 1) trisomy for the 21st pair of chromosomes (95%); 2) translocation variant (3%); 3) mosaic variant (2%). In its clinical manifestations, the trisomy variant does not differ from the translocation variant. Pathognomonic signs of Down syndrome include congenital mental deficiency combined with typical somatic anomalies. In the majority of patients, intelligence is reduced to the level of imbecility (75%), less frequently to idiocy (20%), and as an exception, to the degree of debility (5%). Concrete thinking predominates in these patients. They are unable to master abstract concepts or accounting operations. Active attention and semantic memory are sharply reduced, whereas mechanical memory is better preserved. Speech onset is significantly delayed, and the vocabulary is very limited. Along with this, a relative liveliness is observed. The emotional sphere is preserved. Most patients are gentle and good-natured. "They possess clearly expressed imitative abilities," noted John L. Down. "They can be developed by giving these abilities a practical direction." This facilitates the formation of self-care skills and elementary working techniques.

Children with Down syndrome are born with low body weight and cry quietly. Muscle hypotonia is characteristic; the fontanelles are wide and close later than in healthy peers. The Skull is brachycephalic with a shortened anteroposterior dimension. The face is flattened and the occiput is sloped. The BONES OF THE midface are insufficiently developed. The Nose is short, with a wide, flattened bridge. The palpebral fissures are narrow, with an additional fold in the inner corner of the upper eyelid (epicanthus), similar to Representatives of the Mongoloid race. The profile is flat. The auricles are small, deformed. The Lips are thickened, chapped. The Mouth is open, the Tongue protrudes and is large (papillary hypertrophy). Folds are noticeable on it. Teeth often erupt improperly. Limb anomalies are also typical for these patients. The palms are broad and shortened. The fifth finger is short and curved (it often has a single flexion crease instead of two). Characteristic dermatoglyphic signs of the hand include a transverse flexion crease and a reticular pattern of the palmar papillary lines. The intervals between the First and Second toes are enlarged.

Patients with Down syndrome very frequently exhibit congenital anomalies such as Heart defects, duodenal atresia, rectal dilation, and umbilical hernia. Secondary sexual characteristics are underdevelopment; in males, Spermatogenesis function is impaired, leading to impotence and Infertility.

In the mosaic variant of Down syndrome, clinical signs are manifested to a lesser extent than in trisomy for the 21st pair of chromosomes and the translocation variant.

Treatment of Down syndrome should be initiated as early as possible. Medications stimulating brain function are prescribed (high doses of Vitamins, mineral salts, nootropics). Sedatives, anticonvulsants, and hormonal drugs are used according to indications. The child must be persistently taught to read, count, communicate, practice self-care, and acquire work skills.

Disorders caused by quantitative alterations of sex chromosomes include Klinefelter syndrome, Shereshevsky–Turner syndrome, and trisomy of the X and YY chromosomes.

Klinefelter syndrome (47,XXY) was described in 1942 by H. Klinefelter and co-authors, who designated it as male hypogonadism syndrome. In 1956, P. A. Jacobs and J. A. Strong identified an extra X chromosome in the karyotype of these patients, and sex Chromatin in the nuclei of buccal epithelial Cells. This corresponded to the 47,XXY karyotype. Over time, cases with two extra X chromosomes and a 48,XXXY karyotype, as well as with three extra X chromosomes and a 49,XXXXY karyotype, were discovered. These correspond to two and three sex chromatin bodies, respectively. Mosaic variants of this syndrome with a 46,XY/47,XXY karyotype have also been described.

The incidence of Klinefelter syndrome is 1 in 600 newborn boys, and among patients with oligophrenia, it is 5.5 times higher, i.e., 9.4 per 1000.

Etiology and pathogenesis. The increase in the number of sex chromosomes is caused by non-disjunction of sex chromosomes During the first or Second Stage of oogenesis or The First stage of Meiosis in spermatogenesis. Most commonly, non-disjunction involves two maternal X chromosomes.

Clinical manifestations. At birth, affected boys do not differ from healthy ones. Over time, children with a 47,XXY karyotype show a reduction in intelligence to the level of debility, while the presence of two, three, or more X chromosomes in the karyotype frequently reduces intelligence to the level of imbecility. Mosaic variants of this syndrome with a 46,XY/47,XXY karyotype manifest to a lesser degree. Somatic signs mostly become noticeable during the pubertal or postpubertal period. Body proportions are eunuchoid (facial Hair does not grow; sparse hair cover in the axillary cavities and on the pubis; gynecomastia; testicles are reduced and flaccid). The Penis generally has normal dimensions. A decrease in libido and azoospermia, leading to infertility, are frequently observed.

Diagnosis. Sex chromatin is determined in the nuclei of buccal epithelial cells, and if detected, it indicates Klinefelter syndrome.

Treatment. If signs of insufficient androgenization are present, patients are prescribed Male Sex Hormones.

Shereshevsky–Turner syndrome (45,X) was described in 1925 by N. A. Shereshevsky and in 1938 by Turner. Its incidence is 0.3 per 1000 newborn girls and 0.6 per 1000 patients with oligophrenia.

Etiology and pathogenesis. In 1959, P. Polani and C. E. Ford discovered a 45,X karyotype and the absence of sex chromatin in patients. Subsequently, mosaic variants of this syndrome were described — 45,X/46,XX and 45,X/46,XX/47,XXX. The cause of karyotype anomalies in this case is the non-disjunction of sex chromosomes.

Clinical manifestations. At birth, lymphedema of the subcutaneous tissue on the back of the neck and the dorsal surface of the feet is noticeable. Children have short stature and low body weight. The neck is short with a webbed fold on the back, the chest is broad, and the nipples are widely spaced. Patients exhibit Congenital heart defects, pulmonary artery stenosis, renal anomalies, and fusion and shortening of the vertebrae (Spina bifida). Growth retardation is characteristic of Shereshevsky–Turner syndrome. In adults, height does not exceed 150 cm. Patients have an "antimongoloid" slant of the eyes — the outer corner of the eye is positioned lower than the inner one. Epicanthus is present on the upper eyelid. The ears are low-set and deformed, the neck is broad, and the hairline is low. Patients have an aged appearance. The chest and shoulders are broad, and the pelvis is narrow. In the prepubertal and pubertal periods, underdeveloped external genitalia and Mammary Glands draw attention. Secondary Amenorrhea, decreased libido, and infertility are observed. In the majority of patients, intelligence is reduced to the level of debility, less frequently to imbecility. They are passive, uninitiative, and asthenized.

Diagnosis. The level of sex chromatin is determined. If it is absent, a 45,X karyotype is indicated.

Treatment. Female Sex Hormones are prescribed, which stimulate growth and promote feminization.

Trisomy X syndrome (47,XXX) was described in 1949 by P. A. Jacobs. Its incidence is 1 in 1000 newborn girls. Among patients with mental retardation, it accounts for 0.6%.

Etiology and pathogenesis. The cause of this syndrome is the non-disjunction of sex chromosomes at the first or second stage of oogenesis or the first stage of meiosis in spermatogenesis. In addition to the 47,XXX karyotype, karyotypes with the presence of two and three additional X chromosomes occur, leading to tetrasomy (48,XXXX) and pentasomy (49,XXXXX).

CLINICAL MANIFESTATIONS. Mental retardation (debility) is observed in 75% of women with a 47,XXX karyotype. In cases of tetrasomy and pentasomy for the X chromosomes, mental retardation may reach the level of imbecility.

Diagnosis. Sex chromatin is determined in a buccal scrape from the oral mucosa. The presence of two sex chromatin bodies corresponds to the 47,XXX karyotype, three to 48,XXXX, and four to 49,XXXXX.

YY chromosome syndrome (47,XYY) was described in 1962 by J. Hauschka and co-authors. Its frequency is 1–1.5 per 1,000 newborn boys and from 5 to 150 per 1,000 men with various mental disorders, developmental delay, and antisocial manifestations.

Etiology and pathogenesis. Improper division of the Y chromosomes.

Clinical manifestations. Up to five years of age, children with 47,XYY syndrome do not differ in somatic characteristics from their peers. In the preschool period, there is an enhanced

body growth and an increase in its mass. In almost 80% of cases, developmental delay is detected, reaching varying degrees of debility. This is facilitated by slight inhibition of abstract thinking, cognitive abilities, and speech development disorders. Children are unsociable, and contact with peers is difficult. They are inattentive and restless, and do poorly in school. Emotional-volitional disorders are manifested by spontaneous mood swings, a tendency toward explosiveness, and impulsivity. Over minor triggers, the child becomes aggressive and runs away from school and home. In adolescence, a tendency toward alcohol abuse becomes noticeable.

The most characteristic feature of 47,XYY syndrome is tall stature (on average 186 cm). The physique can be either eunuchoid or athletic. Sometimes an increased androgen content (in the presence of intellectual disability and emotional-volitional instability) may contribute to the commission of offenses and aggressive sexual acts.

Diagnosis. Y chromatin is examined in buccal smears using Fluorescence Cell/15.html">Microscopy. Its content indicates a 47,XYY karyotype.

Treatment and prognosis. Treatment is symptomatic. Particular importance is attached to corrective and educational measures.

Forms of mental retardation caused by Genetic Disorders

Phenylketonuria (Phenylpyruvic Oligophrenia, Fölling disease) was described by A. Fölling in 1934. Its frequency is 1 per 10,000 newborns.

Etiology and pathogenesis. It is inherited in a recessive manner. Hidden carriers are practically healthy people who are heterozygous for the autosomal recessive Gene of phenylketonuria. Every 50th person is a hidden carrier of the phenylketonuria gene. In a marriage between two hidden carriers, every fourth child is born with the phenylketonuria gene in a homozygous state, which leads to the disease. The cause of the ailment is the hereditary absence of the enzyme phenylalanine hydroxylase in the Liver. As a result, one of the Amino Acids—phenylalanine, which is part of food Proteins—is not converted into Tyrosine or melanin. In patients, the phenylalanine content in Blood serum ranges from 150 to 600 mg/L, while in healthy individuals it is 3–40 mg/L.

At the beginning of the second month of life, the deficiency of the enzyme phenylalanine hydroxylase begins to actively manifest in the child. Excess phenylalanine is converted into phenylpyruvic, phenylacetic, and phenyllactic acids, as well as phenylacetylglutamine and phenylethylamine. By the end of the child's second month of life, these metabolic byproducts are excreted in large quantities in the urine. An imbalance of Amino acid METABOLISM, a decrease in the synthesis of serotonin, adrenaline, noradrenaline, dopamine, thyroxine, melanin, as well as nicotinic, amino, and gamma-aminobutyric acids are detected in the body.

Neurohormone deficiency, the accumulation of toxic substances in the body, amino acid metabolism imbalance, impaired glucose utilization, and demyelination of brain Nerve Cells lead to mental development delay and other clinical manifestations of this disease.

Clinical manifestations. The main sign of phenylketonuria is the relentless progression of dementia. Intellectual decline is combined with growth retardation, moderate microcephaly, and such dysplastic features as a high palate, protruding upper jaw, deformed auricles, and epicanthus. In the first half of life, the disease is mostly undetected. However, sometimes from the first weeks, children are very restless, Sleep poorly, cry for no apparent reason, or, conversely, are overly lethargic and drowsy. They do not fix their gaze on objects, do not turn their heads to sound, and begin babbling late.

Regurgitation and vomiting, excessive sweating (with a smell of "mice" or "horse urine," which is explained by The excretion of phenylacetic acid with sweat) are quite frequent and early symptoms. In the second or third month, the hair and iris become lighter. This is especially noticeable in those born as brunettes. 80–90% of sick children are blond, blue-eyed, with fair, dry Skin sensitive to external influences. Diathesis, dermatitis, and eczema are common. Children often have an excess body mass. Their large fontanelle closes early, leading to microcephaly. The pace of formation of mental functions and skills is slowed down. At the age of 4–6 months, children stop joyfully responding to their mother's calls, the reaction to the environment and toys gradually decreases, and irritability, tearfulness, and timidity appear. Passivity is often replaced by restlessness and excitement.

In the second half of life, the delay in mental and motor development becomes more noticeable. Children sit, stand, and walk late, and teeth appear only at 10–11 months. Often, the first signs of the disease are discovered after the baby starts being fed with cow's milk, porridges, cottage cheese, eggs, etc. The appearance of the first symptoms is often facilitated by intercurrent diseases, which are mistakenly regarded as the consequences of "mild" meningitis and meningoencephalitis.

Often, a child who has begun to pronounce individual words subsequently forgets them. Sometimes they babble "mama," "papa," "baba" without addressing them to specific people. Patients are usually lethargic, passive, withdrawn, and unable to concentrate on any game. If they manage to focus their attention for a short time, they execute simple instructions. They know the names of individual objects and body parts. Emotional reactions are impoverished and primitive. They hardly use gestures and facial expressions. They do not want to communicate with parents or peers. At times, they become overly fussy, excited, and impulsive. They repeat the words and actions of others. Their gait is unsteady; they take small steps and frequently stumble and fall.

Without treatment in the first 3–4 months of life, 90–98% of patients experience an intellectual decline to the level of imbecility and idiocy, and 2–10% to debility. If treatment is started in a timely manner, children in most cases do not lag behind in development and attend a regular school. In 30% of untreated patients, epileptic paroxysms appear in the form of "salaam attacks," "HEAD nods," and full-blown epileptic seizures.

Neurological symptoms most frequently manifest as hypertonicity, accompanied by increased tendon Reflexes. Sometimes ataxia, athetoid movements, hyperkinesis, insufficient convergence, strabismus, and a positive Babinski sign are detected. Electroencephalograms record changes characteristic of epilepsy in almost 50% of cases, and pneumoencephalographic studies reveal diffuse Atrophy of the Cerebral Cortex.

Diagnosis. With a positive Fölling test using a 10% iron(III) chloride solution or test strips (Biofan R), the substance turns blue-green or gray-green, and with a test using a 0.3% solution of 2,4-dinitrophenylhydrazine, a bright yellow turbidity forms.

Tests with a 10% iron(III) chloride solution and a 0.3% 2,4-dinitrophenylhydrazine solution can be positive not only in phenylketonuria, but also in histidinemia, tyrosinosis, homocystinuria, maple syrup urine disease, as well as when the urine contains acetone, adrenaline, noradrenaline, bilirubin, salicylates, and chlorpromazine. The diagnosis of phenylketonuria established on The basis of qualitative test results must be confirmed by a blood test (the phenylalanine level must not be lower than 150 mg/L).

Treatment. Meat, fish, cottage cheese, milk, peas, beans, nuts, halva, and flour products are excluded from the diet. Mixtures (berlofen, lafenalac, protein hydrolysate) containing various amino acids except phenylalanine are prescribed. At the age of 1 to 5 years, these preparations are given at a rate of 40 to 20 mg/kg under the control of the blood phenylalanine level (20–90 mg/L). Foods containing low amounts of phenylalanine (sago groats, sunflower and butter, fruits, vegetables) are included in the diet. Dietary control can be relaxed after 6 years, but it is adhered to for a long time.

Prognosis. The probability of having a child with phenylketonuria in a family that already has such a patient is 25%. Women with phenylketonuria often give birth to children with mental retardation, microcephaly, and frequently congenital heart pathology.

During Pregnancy, the concentration of phenylalanine in the blood serum rises above 100 mg/L, which affects fetal development. Children born to these women suffer from oligophrenia in 30% of cases, often combined with epileptic paroxysms and Congenital Malformations. In 5% of them, signs of morphogenesis disorders (hypertelorism, epicanthus, high palate, skeletal and internal organ anomalies) are clearly visualized.

Histidinemia. Described in 1961 by Ghadimi. Its prevalence is approximately 1:16,000 newborns, and it is inherited in an autosomal recessive manner.

Etiology and pathogenesis. Due to the absence of the enzyme histidase, Histidine is not converted into urocanic acid. This leads to elevated levels of histidine, as well as the formation of imidazolepyruvic, imidazolelactic, and imidazoleacetic acids, which exert a toxic effect on the central nervous system.

CLINICAL manifestations. The disorder is predominantly detected during the second half of an infant's first year of life. Affected individuals have fair skin and hair, and blue eyes. Mental retardation develops progressively, reaching a mild to moderate degree of debility. Notable neurological disorders include speech development Impairment of the motor alalia type, intention tremor, and ataxia. Epileptic seizures occur in 10% of cases. Radiographs frequently reveal signs of Hydrocephalus.

Diagnosis. The clinical characteristics of histidinemia are very similar to those of phenylketonuria. If imidazolepyruvic acid is present in the urine, the Felling test yields a positive reaction, though not immediately as in phenylketonuria, but within 1—3 min. Additionally, the 2,4-dinitrophenylhydrazine test is performed. Differentiation between these conditions is based on the fact that in histidinemia, plasma histidine levels are elevated to 0.04—0.09 g/L, whereas phenylalanine levels remain within the normal range. Furthermore, the skin content of histidase is determined.

Treatment. Pathogenetic Therapy utilizing a special diet (incorporating histidine-free hydrolysates).

Galactosemia. The prevalence of galactosemia ranges from 1:10,000 to 1:40,000 of the population.

In 1961, R. Krutý and A. Weinberg discovered a deficiency of the enzyme galactose-1-phosphate uridyltransferase in this condition.

Etiology and pathogenesis. In classic galactosemia, a deficiency of the enzyme galactose-1-phosphate uridyltransferase leads to elevated levels of galactose-1-phosphate and galactose. High concentrations of galactose are accompanied by its excretion in the urine, as well as the formation of galactitol, which, together with galactose, causes cataracts. The accumulation of glucose-1-phosphate exerts a hepatotoxic effect and causes delayed mental development.

Clinical manifestations. As soon as the newborn begins receiving breast milk, dyspeptic disorders appear, manifesting as vomiting, diarrhea, and dehydration. Hepatosplenomegaly, liver cirrhosis, cataracts, delayed mental development, and convulsive twitching develop progressively. The child gains weight slowly.

Diagnosis. Urinary galactose levels reach as high as 2.0 g/L. A deficiency of the enzyme galactose-1-phosphate uridyltransferase is detected in erythrocytes.

Prevention and treatment. Early treatment of galactosemia, elimination of milk from the diet, and switching to a galactose-free diet help improve the child's physical condition and prevent the progression of dementia. Soy milk and other soy-based products, fruits, and vegetables are recommended for Nutrition. A casein diet is also beneficial.

Fructosuria is an inherited intolerance to fructose. The condition was described in 1956 by Chambers and Pratt. It is inherited in an autosomal recessive manner, with a frequency of approximately 1:40,000 of the population.

Etiology and pathogenesis. Fructosuria is caused by a deficiency of fructose-1-phosphate aldolase in the liver. This leads to the accumulation of fructose and fructose-1-phosphate in the blood and Tissues, which exert toxic effects and disrupt The process of glucose formation from Glycogen.

Clinical manifestations. The disease is usually detected during the Introduction of fruit juices into the infant's diet. Vomiting, along with an aversion to juices and fruits, appears. Hypotrophy develops, accompanied by delayed physical development, hepatomegaly, and jaundice. Hypoglycemic crises may occur. Against this Background, mental development slows down, generally reaching the degree of debility.

Diagnosis. Seliwanoff's test is used along with the determination of urinary fructose content, while blood levels of fructose and fructose-1-phosphate are measured (which are elevated in this condition).

Treatment. A diet excluding fruit juices, fruits, sweet vegetables, honey, and sugar is prescribed.

Amaurotic idiocy, or Tay-Sachs disease, belongs to lipid storage disorders. Its frequency is 1:250,000 of the population. It is inherited in an autosomal recessive manner.

Etiology and pathogenesis. The inability of hexosaminidase A to degrade GM₂ ganglioside leads to a sharp increase (sometimes up to 100-fold) in its level within brain cells, subsequently resulting in their destruction. Microglial cells proliferate, swell, and become engorged with large granules, which causes dementia. The same impairments in the retinal nerve cells rapidly lead to optic atrophy, a sharp decrease in visual acuity, amaurosis, and the formation of a typical cherry-red spot in the macula.

CLINICAL manifestations. Following 4—6 months of normal development, the child exhibits motiveless monotonous crying, lethargy, and adynamia. The infant is unable to hold its head up. Concurrently, an increased reaction to sounds ("startle reflex") appears as an early sign of the disorder.

Over time, nystagmus, strabismus, anisocoria, paresis and paralysis of the limbs develop, muscle tone increases, and tonic-clonic paroxysms occur. Within a few months, dementia progresses to the stage of profound mental retardation (idiocy).

Visual acuity declines rapidly, leading to complete blindness. Fundoscopic examination reveals pathognomonic signs such as optic atrophy and a cherry-red spot in the macular region. Gradually, physical exhaustion reaches the stage of cachexia. Affected individuals die at the age of 3—4 years.

Treatment. No specific therapy has been developed. The basis of preventing amaurotic idiocy is the identification of hidden carriers, as well as prenatal diagnosis using amniocentesis.

Martin-Bell syndrome. Atypical mental retardation was described in 1943 by J. Martin and J. Bell. Attention was drawn to this pathology only in the 1960s, and in the 1990s it was classified as a distinct disease. The frequency of Martin-Bell syndrome is 1:2,000 newborn boys, and among boys with pronounced mental retardation, it is 6—10%. It is inherited in a recessive manner linked to fragile sites on the X chromosome. There is also a hypothesis regarding The Role of Connective Tissue formation or Metabolic Disorders in the genesis of this condition.

Etiology and pathogenesis. Based on the appearance of the X chromosome fragile site phenomenon in a low-folate medium, it is hypothesized that folate deficiency plays a certain role in the pathogenesis of mental retardation.

Clinical manifestations. Intellectual underdevelopment corresponds to mild to moderate mental retardation, frequently combined with emotional lability, excitability, and motor disinhibition. Despite intellectual developmental delay, the emotional sphere remains relatively preserved. This is manifested by adequate reactions in various situations, as well as a deep attachment to specific individuals. Against the background of clinical manifestations, 40% of patients exhibit schizophreniform symptoms in the form of autism and catatonic features such as bizarre stereotyped postures and monotonous movements (jumping, clapping, tapping, etc.).

Mild dysplastic features are observed. The patient presents with macrocephaly characterized by a high and broad forehead, and large, prominent ears. The face is elongated with a prognathic Mandible; the midface is flattened due to a broad nose with a rounded tip. The fingers, toes, palms, and soles are broad. The skin is hyperextensible, and the joints exhibit hypermobility. The primary somatic feature is macroorchidism, which is unrelated to endocrine disorders.

Neurological manifestations are characterized by muscular hypotonia and mild ataxia. Epileptic seizures occur in 10% of cases. Characteristic electroencephalographic (EEG) findings include the absence of the $\alpha$-rhythm and enhanced $\delta$-activity.

Diagnosis. The diagnosis is established based on psychopathological, somatic, and electroencephalographic features, as well as the results of cytogenetic studies (fragility of the X chromosome).

Treatment. Given the role of folate deficiency in the pathogenesis of Martin–Bell syndrome, treatment involves high doses of Folic acid (2–30 mg/day). This contributes to the resolution of schizophrenia-like symptoms, though it does not reverse intellectual disability.

Forms of intellectual disability of hereditary-exogenous genesis (microcephaly, cretinism)

Prenatal, perinatal, and postnatal pathogenic factors leading to dementia are distinguished.

Perinatal brain injuries include maternal infections such as cytomegalovirus infection, rubella, herpes, Toxoplasmosis, Listeriosis, and Syphilis. The Development of encephalopathy in the child may be promoted by gestosis, hypothyroidism, uterine Hemorrhage, placental insufficiency, radiation injuries, fetal alcohol syndrome, and the teratogenic effects of medications. They may also be caused by birth trauma, asphyxia, acidosis, hypoglycemia, hyponatremia, and thermal stress.

Postnatal brain injuries are diverse. These include childhood infections, nutritional disorders, post-vaccination complications, bilirubin encephalopathy (kernicterus), and others.

In addition to organic causes of dementia, sociocultural and environmental influences must also be considered. A lack of intellectual stimulation typically leads to mild dementia.

Microcephaly. A significant contribution to the Description of the disease was made by I. P. Merzheevsky (1871), V. A. Betz (1871), and S. S. Korsakov (1894). Microcephaly is a heterogeneous condition. True (hereditary) and secondary (cerebropathic exogenous) forms of microcephaly are distinguished. The prevalence of microcephaly ranges from 1:2,000 to 1:10,000 of the population.

Etiology and pathogenesis. True microcephaly is inherited in an autosomal recessive and polygenic manner. Its prevalence ranges from 1:25,000 to 1:40,000 of the population, while the carrier frequency for heterozygotes is 1:100. One-third of heterozygous microcephaly carriers exhibit intellectual disability despite having a normal brain size.

The exogenously induced form of microcephaly arises from embryopathy due to intrauterine exposure to teratogenic factors such as viral infections (rubella, cytomegalovirus infection), ionizing radiation, Hypoxia, and Carbon monoxide poisoning.

Clinical manifestations. Pathognomonic physical and mental signs of microcephaly include a cranial circumference of up to 50 cm in affected individuals. Brain mass is reduced by 25% or more, primarily affecting the frontal and parietal lobes. The forehead is low and sloping. The typical appearance of patients is characterized by a disproportion between the reduced cranial vault and the normal-sized facial Structure and stature. Intellectual impairment typically reaches the level of profound mental retardation (idiotia), and less frequently, mild retardation (debilitas).

In cases of profound mental retardation, some individuals retain articulated speech to a certain extent, yet they fail to comprehend the meaning of their own words or the speech of others. Intonation and facial expressions accompanying words are of greater importance to these patients. While capable of counting, they are unable to concentrate. Their perceptions change rapidly and are not retained in memory. The emotional sphere is relatively better developed. Motor skills are preserved to a fair degree; patients can easily climb trees and learn to ride a bicycle.

Furthermore, these individuals react vividly and emotionally to certain events, displaying clear feelings of sympathy. A heightened mood is most common. They are emotionally unstable and prone to anger.

Taking into account the specific temperament and activity levels, patients are divided into torpid and erethic types. Torpid patients are sluggish, apathetic, and hypoactive. They show no interest in their surroundings, can sit in the same posture for prolonged periods, and it is difficult to capture their attention even briefly. They greet those who are kind to them with a smile and a friendly demeanor.

Erethic patients are characterized by liveliness, mobility, and restlessness. Their movements are varied and coordinated, and their facial expressions are animated. They readily imitate the movements, gestures, facial expressions, and intonations of others. Some exhibit satisfactory mechanical memory. They give the impression of being interested rather than inquisitive. A heightened mood with a Touch of euphoria prevails. Emotional displays are unstable and easily escalate into angry affective outbursts.

Signs of organic nervous system damage are absent in true microcephaly. In secondary microcephaly, focal neurological symptoms and epileptic seizures are frequently observed. Patients are typically short in stature with a disproportionate body structure. Secondary sex characteristics are poorly developed in males and delayed in females.

Treatment. There is no specific treatment. Symptomatic therapy (anticonvulsants, sedatives) is administered as needed.

Cretinism is a condition of arrested mental development caused by hypothyroidism.

Etiology and pathogenesis. Both hereditary forms of the disease, inherited in an autosomal recessive manner, and exogenous forms are distinguished. The latter are caused by such adverse factors during the prenatal or early postnatal periods as iodine deficiency, thyroid and pituitary disorders, autoimmune conditions, infections, and intoxication processes. Insufficient supply of THYROID HORMONES leads to goiter development and delayed physical and mental maturation.

Clinical manifestations. Children show delays in physical and mental development from an early age. The degree of intellectual impairment ranges from mild mental retardation (debilitas) to moderate (imbecilitas) and even profound (idiotia) retardation. Patients are characterized by short stature and a disproportionate body structure (stocky, with a short thick neck, short limbs, wide hands, and broad feet). In addition, multiple dysplasias are observed, including an enlarged skull, a low forehead, a depressed nasal bridge, hypertelorism, deformed ears, thickened lips, and macroglossia. Patients with cretinism frequently exhibit impaired ossification, leading to lordosis, tibial bowing, and bone fragility. Thyroid atrophy often leads to myxedematous syndrome, caused by the accumulation of mucinous substance in the skin and subcutaneous tissue. This results in facial edema and skin induration. Hypotension and bradycardia are characteristic. The Gonads are underdeveloped, and secondary sex characteristics emerge with a delay.

Diagnostics. For early diagnosis of cretinism, screening programs (assessing thyroid hormone levels) as well as functional tests (determining iodine concentration in blood and urine) are utilized.

Treatment. Early administration of thyroidin in escalating doses (from 5 to 50–75 mg per day) prevents the development of severe physical and mental impairments.

EXOGENOUSLY INDUCED FORMS OF MENTAL RETARDATION

This group includes: fetal alcohol syndrome, and intellectual disability resulting from immunogenetic incompatibility due to ABO and Rh factors.

Fetal alcohol syndrome (also known as fetal alcohol effect or embryofetopathy) was first described in 1973 by K. Jones and D. Smith. Its incidence ranges from 0.5 to 2.0 per 1,000 newborns, and reaches 10–20% among individuals with mild intellectual disability (debility). The risk of developmental impairment, its severity, and the morphogenesis of fetal alcohol syndrome depend on The amount of alcohol consumed and the gestational age. Among women with alcoholism, 32.0% of children are born with fetal alcohol syndrome, compared to 14.0% of women who consume alcohol moderately.

Etiology and pathogenesis. The primary cause of this syndrome is alcohol consumption, predominantly during the first 3 months of pregnancy. Ethyl alcohol and its metabolites readily cross the placenta as well as the Embryonic and Fetal membranes, adversely affecting development. Furthermore, alcohol disrupts the placental transport of Essential Amino Acids and zinc, which are critical for Protein Synthesis, leading to intrauterine growth restriction. This may be further exacerbated by protein and vitamin deficiencies in the mother's body.

CLINICAL manifestations. Such infants are often born with signs of intrauterine growth restriction and neonatal abstinence syndrome. During the first 3 days of life, hyperactivity, insomnia, and tremors of the upper and lower extremities are observed. Over the next 2–3 days, lethargy becomes the dominant feature.

Pathognomonic symptoms of fetal alcohol syndrome include discrepancies in height, development, and body weight during the pre- and postnatal periods, as well as craniofacial anomalies and delayed mental development.

At birth, the average body weight of these children does not exceed 2,220 g, and their length is no more than 46 cm, which corresponds to 32–33 weeks of gestation. Deficits in body weight tend to outweigh height retardation in subsequent years. At 5 years of age, a child's height corresponds to that of a 3-year-old, and their body weight to that of a 2-year-old. The adult height of affected males does not exceed 160 cm.

Craniofacial dysmorphism is characterized by a reduced head circumference. The forehead is low, the palpebral fissures are short and narrow, and microphthalmia is present. Epicanthic folds on the upper eyelids, ptosis, myopia, strabismus, and retinal vessel tortuosity are also common. Affected individuals typically exhibit hypoplasia and concavity of the midface. The nasal bridge is broad and flattened, the eyes are widely spaced, the nose is shortened, the nasolabial fold is smoothed out, and the distance between the nose and the upper lip is increased. The lips are thin and red, and the chin is small.

Signs of fetal alcohol syndrome may be combined with auricular deformities, congenital heart defects, Genitourinary system abnormalities, hernias, and hemangiomas. Neurological anomalies often manifest as reflex Asymmetry and muscle hypotonia.

Behavioral abnormalities become noticeable during the neonatal period, including tearfulness, irritability, and hyperactivity. Later in life, hyperactivity is accompanied by a lack of attention span, intellectual impairment down to the level of mild mental disability (debility), and poor social adaptation.

During adolescence, some patients exhibit a euphoric mood, talkativeness, playfulness, and sexual disinhibition, whereas others display a dysphoric, irritable mood, aggressiveness, cruelty, and a propensity for delinquent behavior.

Prevention and Treatment

Primary prevention measures include: premarital Genetic Counseling; improved medical care for pregnant women and monitoring of fetal development; enhancement of environmental and socio-economic living conditions; and the prevention of peri- and postnatal injuries. Secondary prevention of intellectual disability involves: improved neonatal screening; timely detection of disorders associated with intellectual disability; early treatment thereof; and identification of socially deprived children to provide specialized educational programs.

Pathogenetic treatment has not yet been established. Therapy for intellectual disability comprises both biological and psychological approaches. Biological therapy aims to compensate for metabolic abnormalities. Pharmacological agents are prescribed to stimulate cognitive functions and treat comorbid psychiatric disorders. Psychotherapy involves counseling for parents and family members, behavioral therapy, and individual supportive therapy. Families raising children with intellectual disabilities require comprehensive societal support—both moral and material. Such families are managed by general practitioners, medical and social support services, and social security agencies. Approaches to patients with intellectual disability should be based on two core principles: 1) individualization (every patient should be understood and stimulated); and 2) normalization (every patient with intellectual disability should live as full a life as possible). Implementing these principles requires a well-structured medical, psychological, educational, and social support system. This includes organizing specialized groups in kindergartens, providing education in special schools, and offering employment in sheltered workshops or specialized industrial units, among other measures.

Prognosis

The prognosis depends on the etiology of the disorders, their clinical characteristics, and the micro-social environment. In differentiated forms of intellectual disability, timely diagnosis and appropriate etiopathogenetic treatment are of paramount importance. The Use of specialized diets and metabolism-correcting medications can sometimes slow the progression of the destructive process. Based on clinical symptomatology, the dynamics of intellectual disability are classified as stationary, progressive, or regressive. Its progression is determined by concurrent personality and psychiatric disorders. The poorest prognosis is observed in patients with dysphoric and moria-like personality disorders. Under unfavorable micro-social conditions, individuals with intellectual disability may occasionally exhibit behavioral disorders, which can be triggered by insufficient stimulation or distress. The prognosis is more favorable when behavior is successfully modified, and practical skills are developed and reinforced.

Expert Evaluation

Medical and social expert evaluation. The majority of individuals with intellectual disabilities require social support and education. During medical and social assessments, factors such as the level of mental development, comorbid psychiatric and somatoneurological disorders, and the micro-social environment must be taken into account.

In forensic psychiatric evaluations of individuals with intellectual disabilities who have committed offenses, it is necessary to assess not only the degree of mental underdevelopment but also comorbid psychiatric disorders and the motivation behind the illegal acts. If legal norms are poorly comprehended and actions stem from impulsive motives, patients may be declared legally insane (non compos mentis) based on criteria of intellectual disability or other pathological conditions, leading to exculpation. Legal capacity is assessed using criteria related to intellectual disability. Expert evaluations involving witnesses and victims are determined based on a combination of clinical and situational indicators.

Military medical evaluations are governed by Article 20 of the Order of the Ministry of Health of Ukraine No. 2 dated January 4, 1994. Clause "a" ("unfit for military service") encompasses all forms of profound, severe, and moderate intellectual disability. Clause "b" ("fit for restricted service") applies to individuals with intellectual disability at the level of mild debility. This category of conscripts must undergo inpatient medical examination.

The determination of intellectual level in all types of expert evaluations must be based on available information, including data on the clinical course of the pathology, adaptive behavior, and performance on psychometric tests. The use of intelligence and social maturity tests must be standardized and consistent with established methodologies.