PM – Genetic, Nutrition, Metabolic, Psychiatry

Serotonin imbalance is most closely associated with depression, impacting mood, emotions, and sleep. Dopamine imbalance is linked to schizophrenia and Parkinson‘s disease. GABA is related to anxiety disorders due to its role in inhibitory neurotransmission. Acetylcholine imbalance is associated with Alzheimer‘s disease.

Impaired social interaction is a core symptom of Autism Spectrum Disorder, affecting the ability to communicate and interact. Hallucinations are typically associated with psychotic disorders. Mood swings can occur in bipolar disorder. Anhedonia is often seen in depression.

Bipolar disorder is characterized by the presence of both manic and depressive episodes. Major depressive disorder involves depressive episodes only. Generalized anxiety disorder is characterized by persistent and excessive anxiety. Schizophrenia involves symptoms like delusions and hallucinations.

Recurrent, unwanted thoughts (obsessions) and repetitive behaviors (compulsions) are hallmarks of OCD, aimed at preventing distress or a feared event. Flashbacks are characteristic of PTSD. Intrusive thoughts without compulsions may suggest an anxiety disorder. Delusions are false beliefs seen in psychotic disorders.

Psychomotor retardation, a slowing down of thought and physical movements, is not typical of ADHD, which is characterized by hyperactivity, impulsivity, and inattention. Hyperactivity, Impulsivity, and Inattention are core symptoms of ADHD.

An intense fear of gaining weight and a distorted body image, leading to severe restriction of food intake, characterizes anorexia nervosa. Binge eating followed by purging characterizes bulimia nervosa. Excessive eating without compensatory behaviors describes binge eating disorder. Preoccupation with food and high body mass index (BMI) may suggest overeating or obesity, not anorexia.

Schizophrenia; this theory suggests that receiving contradictory messages from significant others in a position of authority can contribute to schizophrenia. Bipolar disorder involves mood swings. Borderline personality disorder involves unstable relationships, self-image, and affects. Dissociative identity disorder involves two or more distinct identities.

Autism Spectrum Disorder; echolalia is the repetitive vocalization of words or phrases heard by the individual, common in autism. Tourette syndrome involves vocal and motor tics. Schizophrenia can involve disorganized speech but not specifically echolalia. Alzheimer’s disease involves memory loss primarily, not echolalia.

Antisocial personality disorder; individuals often display a lack of empathy and a tendency towards deceitfulness or manipulation. Narcissistic personality disorder involves grandiosity. Avoidant personality disorder is characterized by social inhibition. Obsessive-compulsive personality disorder involves a preoccupation with orderliness and control.

Hypnagogic hallucinations are vivid perceptual experiences that occur at the onset of sleep (as one is falling asleep).

They are common in narcolepsy but can also occur in healthy individuals.

Hypnopompic hallucinations occur upon awakening from sleep.

Jactatio nocturna capitis is a benign sleep-related movement disorder, unrelated to hallucinations.

A rapid shift from one topic to another, often seen in manic episodes of bipolar disorder, indicating a disorganized thought process. Circumstantiality involves unnecessary detail but eventually reaching the point. Tangentiality means never reaching the intended point. Loose associations involve a disorganized thought process but less rapid shifting than flight of ideas.

Parasomnias, which involve abnormal movements, behaviors, emotions, perceptions, or dreams occurring while falling asleep, sleeping, between sleep stages, or during arousal from sleep. Insomnia involves difficulty falling or staying asleep. Narcolepsy involves daytime sleep attacks. Sleep apnea involves breathing interruptions during sleep.

Thiamine (Vitamin B1) deficiency leads to beriberi, affecting the nervous system and heart. Niacin (Vitamin B3) deficiency causes pellagra. Vitamin C deficiency results in scurvy. Iron deficiency leads to anemia.

The formation of the mature Vitamin D hormone occurs in the kidney after second hydroxylation

Degree of respiratory compensation in simple metabolic acidosis is predicted by PaCO2
= (1.5 x
[HCO3–]) + 8 ± 2. Thus, PaCO2
decreases by 1.25 mm Hg for each mmol/L decrease in [HCO3–].
Values for PaCO2
<24 or >28 mmHg define a mixed disturbance (metabolic acidosis and respiratory
alkalosis or metabolic alkalosis and respiratory acidosis, respectively)

Marasmus is a form of severe protein–energy malnutrition due to a prolonged deficiency of both calories and protein.

Key features:

Severe muscle wasting and loss of subcutaneous fat.

Marked weight loss (usually weight <60% of expected for age).

Often has a voracious appetite if the child is alert and active.

Hepatomegaly is not typical of marasmus; it is more characteristic of kwashiorkor, where fatty infiltration of the liver occurs due to protein deficiency.

Omega-3 fatty acids are known to reduce inflammation and are associated with a lower risk of heart disease. Saturated fats can increase LDL cholesterol. Trans fats are associated with an increased risk of heart disease. Monounsaturated fats are healthy fats that can improve cholesterol levels.

In Liddle’s syndrome, activating mutations occur in epithelial Na+ channel causing increase in Na+
reclamation that produces hypokalemia, hypertension, and metabolic alkalosis.

Inherited and metabolic disorders that can lead to chronic liver disease include 1-Antitrypsin
deficiency, Alagille’s syndrome, Biliary atresia, Familial intrahepatic cholestasis (FIC) types 1-3,
Fanconi’s syndrome, Galactosemia, Gaucher’s disease, Glycogen storage disease,
Hemochromatosis, Hereditary fructose intolerance, Hereditary tyrosinemia, Wilson’s disease.

The genetic defect in MEN I is in the long arm of chromosome 11 (11q11-q13)

Genepolymorphisms may include alcohol dehydrogenase, cytochrome P4502E1, and those associated
with alcoholism (twin studies).

Folic acid is the common name for pteroylmonoglutamic acid.

Cystic Fibrosis is caused by mutations in the CFTR gene, affecting chloride ion transport. BRCA1 mutations are linked to breast cancer. HBB mutations cause sickle cell anemia. FMR1 mutations lead to Fragile X syndrome.

Huntington‘s disease follows an autosomal dominant pattern, meaning a single copy of the mutated gene can cause the disorder. Autosomal recessive disorders require two copies of the mutated gene. X-linked recessive disorders are mostly seen in males. Mitochondrial inheritance comes from the mother only.

More males are affected because they have only one X chromosome. Females must inherit two copies of the mutated gene to be affected. Equal male and female distribution occurs in autosomal disorders. Affected fathers to sons transmission does not happen in X-linked recessive. Mother to all daughters transmission is seen in mitochondrial inheritance.

A nonsense mutation introduces a premature stop codon, leading to a truncated, often nonfunctional protein. Missense mutations result in a single amino acid change. Silent mutations do not alter the amino acid sequence. Frameshift mutations alter the reading frame, affecting all downstream amino acids.

The p53 gene acts as a tumor suppressor, preventing the proliferation of cells with damaged DNA. Oncogenes promote cell division. Growth factors stimulate cell growth and division. Telomerase maintains telomere length, associated with cell aging and cancer.

Down syndrome is caused by trisomy 21, leading to a characteristic set of physical and intellectual features. Turner syndrome involves a missing X chromosome in females. Klinefelter syndrome is characterized by an extra X chromosome in males. Triple X syndrome involves an extra X chromosome in females.

Nihilistic ideas involve the belief that oneself, parts of the body, or the world do not exist or are about to be destroyed.

When these ideas take a delusional form, they are known as Cotard’s syndrome, often presenting with severe depressive episodes with psychotic features.

They are most commonly associated with severe depression, especially in psychotic depression, though they can occasionally occur in schizophrenia.

DiGeorge syndrome results from a microdeletion on chromosome 22q11.2, affecting development. Williams syndrome involves deletion on chromosome 7. Prader-Willi syndrome and Angelman syndrome are caused by deletions or imprinting errors on chromosome 15.

Leber‘s hereditary optic neuropathy is an example of a mitochondrial inheritance disorder, affecting vision. Hemophilia follows an X-linked recessive pattern. Cystic fibrosis is autosomal recessive. Marfan syndrome is autosomal dominant.

Marfan syndrome involves connective tissue defects, leading to tall stature and cardiovascular risks. Achondroplasia results in dwarfism. Ehlers-Danlos syndrome affects connective tissue, leading to skin hyperelasticity and joint hypermobility. Osteogenesis imperfecta leads to brittle bones.

Dystrophin gene mutations cause Duchenne Muscular Dystrophy, leading to muscle weakness. CFTR mutations cause Cystic Fibrosis. MECP2 mutations lead to Rett syndrome. FMR1 mutations cause Fragile X syndrome.

Variable expressivity explains the differing severity of symptoms in sickle cell disease. Incomplete penetrance would mean not all carriers show symptoms. Anticipation involves symptoms becoming more severe in subsequent generations. Linkage disequilibrium describes the non-random association of alleles at different loci.

PKU is inherited in an autosomal recessive manner, requiring two copies of the mutated gene to manifest the disease. Autosomal dominant disorders require only one mutated gene. X-linked dominant disorders are rare and can be passed by either parent. Mitochondrial inheritance comes from the mother only.

Gynecomastia can result from an imbalance between estrogen and androgen activity. The typical hormonal workup includes:

Testosterone – to detect androgen deficiency.

Estradiol – to assess excess estrogen states.

Luteinizing hormone (LH) – to evaluate pituitary–gonadal axis and differentiate primary from secondary hypogonadism.

Prolactin is not routinely measured in gynecomastia unless there are signs of hypogonadotropic hypogonadism or pituitary disease (e.g., galactorrhea, headache, visual defects). Hyperprolactinemia causes decreased testosterone indirectly but is not a common direct cause of gynecomastia, hence least useful in routine evaluation.

Colour blindness → X-linked recessive.

Haemophilia → X-linked recessive (most commonly Hemophilia A & B).

Phenylketonuria (PKU) → Autosomal recessive (mutation in PAH gene).

Tuberous sclerosis → Autosomal dominant (mutations in TSC1 or TSC2 genes, leading to hamartomas in multiple organs).

Trichobezoar is a compact mass of swallowed hair found in the stomach, usually in adolescent or young females with psychiatric disorders such as trichotillomania (hair-pulling) and trichophagia (hair-eating).

It may extend into the small intestine in severe cases (Rapunzel syndrome).

Hair is indigestible, so it accumulates and forms a ball that can cause gastric outlet obstruction.

Congenital adrenal hyperplasia (CAH) is caused by a deficiency in 21-hydroxylase, leading to cortisol production issues. Addison‘s disease involves adrenal insufficiency. Cushing‘s syndrome is characterized by excess cortisol. Pheochromocytoma involves a tumor that increases catecholamine production.

Confabulation is the unconscious fabrication of false memories to fill in memory gaps, usually seen in organic amnestic states such as Korsakoff’s syndrome (due to thiamine deficiency, often in chronic alcoholism).

It is not intentional lying—the patient believes the fabricated details are true.

It is not typically a feature of delirium, though delirium can cause disorientation and memory impairment.

Niemann–Pick disease is a lysosomal storage disorder caused by deficiency of sphingomyelinase (in types A and B) leading to accumulation of sphingomyelin in macrophages.

It is inherited in an autosomal recessive pattern.

Clinical features include hepatosplenomegaly, progressive neurodegeneration, failure to thrive, and “foamy” macrophages on histology.

Type C is due to a defect in cholesterol trafficking (NPC1/NPC2 gene), not enzyme deficiency.

Obesity is a major risk factor for NAFLD, leading to fat accumulation in the liver without alcohol consumption. Alcohol consumption is related to alcoholic liver disease. Viral hepatitis leads to liver inflammation due to a virus. Autoimmune hepatitis involves the immune system attacking liver cells.

Galactose-1-phosphate uridyltransferase deficiency leads to classic Galactosemia, causing issues with galactose metabolism. Beta-galactosidase deficiency results in GM1 gangliosidosis. Glucose-6-phosphate dehydrogenase deficiency leads to hemolytic anemia. Aldolase B deficiency causes hereditary fructose intolerance.

Phenylketonuria (PKU) is due to deficiency of phenylalanine hydroxylase (or its cofactor tetrahydrobiopterin), leading to accumulation of phenylalanine and its metabolites.

These metabolites give the characteristic “mousy” or musty odor to urine, sweat, and breath.

Other features: developmental delay, seizures, hypopigmentation (due to decreased melanin synthesis), eczema.

Maple syrup urine disease has a burnt sugar odor, tyrosinemia has a rancid odor, and homocystinuria does not have a distinctive urine smell.

Mutations in the ATP7B gene cause Wilson‘s disease, leading to copper accumulation in the body. CFTR mutations cause Cystic Fibrosis. HFE gene mutations are associated with Hereditary Hemochromatosis. ALDH2 deficiency is linked to alcohol metabolism issues.

Metabolic alkalosis is associated with hypokalemia due to K+ redistribution as well as excessive renal K+
loss.

Presentation of vitamin E deficiency resemble those of Friedreich’s ataxia.

Deficiency of phenylalanine hydroxylase in PKU leads to the accumulation of phenylalanine. Untreated PKU can lead to intellectual disability, seizures, and behavioral problems due to the accumulation of phenylalanine. Mental sharpness implies cognitive well-being, opposite of PKU effects. Muscle hypertrophy is not associated with PKU. Enhanced physical endurance is unrelated to the metabolic effects of PKU.

Cortisol deficiency in Addison‘s disease leads to symptoms like fatigue, weight loss, and low blood pressure. Insulin deficiency leads to diabetes mellitus. Thyroid hormone deficiency results in hypothyroidism. Growth hormone deficiency affects growth and body composition.

Prader–Willi syndrome → deletion/mutation of paternal 15q11–q13 (maternal allele imprinted).

Features: hypotonia in infancy, feeding difficulties → later hyperphagia, obesity, hypogonadism, short stature.

Angelman syndrome → deletion of maternal 15q11–q13 (paternal allele imprinted), features include inappropriate laughter (“happy puppet”), seizures, ataxia.