Rishi Desai, MD, MPH

Pyruvate dehydrogenase deficiency

Chapter 49 Mitochondrial Disease  TREATMENT OTHER INTERVENTIONS  ▪ Aerobic exercises ▪ Coenzyme Q10, L-carnitine, creatine supplementation ▪ MELAS ▫ Intravenous arginine hydrochloride with saline, ﬂuids with dextrose ▪ Avoid ▫ Valproic acid, tetracyclines, barbiturates, chloramphenicol, aminoglycosides, metmorﬁn  PYRUVATE DEHYDROGENASE DEFICIENCY osms.it/PDH-deficiency PATHOLOGY & CAUSES ▪ X-linked disease characterized by abnormal pyruvate metabolism  CAUSES  ▪ E1 alpha gene mutation ▫ Pyruvate dehydrogenase E1 alpha subunit deﬁciency → ↓ production of acetyl-coenzyme A (CoA) → limited citrate production → citric acid cycle (Krebs cycle) impairment ▪ Impaired Krebs cycle ▫ Energy production disorder; brain needs energy from Krebs cycle → neurological symptoms ▫ Pyruvate accumulation → transformation to lactate, alanine → lactate buildup → lactic acidosis → metabolic symptoms ▪ Residual activity of enzyme determines clinical presentation ▫ Severe deﬁciency → congenital brain malformations  ▫ Moderate deﬁciency → neurological symptoms onset in infancy/later childhood  COMPLICATIONS  ▪ Intellectual disability, microcephaly, blindness ▪ Leigh syndrome ▫ Gray matter degeneration, capillary proliferation, focal necrosis  SIGNS & SYMPTOMS ▪ Metabolic disorders ▫ Lethargy, poor feeding, mental/ psychomotor delay ▪ Neurological symptoms ▫ Ataxia, hypotonia, progressive encephalopathy, abnormal eye movements, seizures, dystonia ▪ Acidosis respiratory symptoms ▫ Dyspnea, Cheyne–Stokes breathing, respiratory failure  OSMOSIS.ORG 285   

Amino acid metabolism

Nitrogen and urea cycle

Citric acid cycle

Electron transport chain and oxidative phosphorylation

Gluconeogenesis

Glycogen metabolism

Glycolysis

Pentose phosphate pathway

Physiological changes during exercise

Cholesterol metabolism

Fatty acid oxidation

Fatty acid synthesis

Ketone body metabolism

Biochemistry and metabolism

Alkaptonuria

Cystinuria (NORD)

Hartnup disease

Homocystinuria

Maple syrup urine disease

Ornithine transcarbamylase deficiency

Phenylketonuria (NORD)

Essential fructosuria

Galactosemia

Glucose-6-phosphate dehydrogenase (G6PD) deficiency

Hereditary fructose intolerance

Lactose intolerance

Abetalipoproteinemia

Familial hypercholesterolemia

Hyperlipidemia

Hypertriglyceridemia

Glycogen storage disease type I

Glycogen storage disease type II (NORD)

Glycogen storage disease type III

Glycogen storage disease type IV

Glycogen storage disease type V

Mucopolysaccharide storage disease type 1 (Hurler syndrome) (NORD)

Mucopolysaccharide storage disease type 2 (Hunter syndrome) (NORD)

Fabry disease (NORD)

Gaucher disease (NORD)

Krabbe disease

Leukodystrophy

Metachromatic leukodystrophy (NORD)

Niemann-Pick disease type C

Niemann-Pick disease types A and B (NORD)

Tay-Sachs disease (NORD)

Cystinosis

Disorders of amino acid metabolism: Pathology review

Disorders of carbohydrate metabolism: Pathology review

Disorders of fatty acid metabolism: Pathology review

Dyslipidemias: Pathology review

Glycogen storage disorders: Pathology review

Lysosomal storage disorders: Pathology review

Metabolic disorders

Biochemistry

Carbohydrates and sugars

Fats and lipids

Proteins

Carbohydrates, fat and protein

Excess Vitamin A

Excess Vitamin D

Vitamin D deficiency

Vitamin K deficiency

Kwashiorkor

Marasmus

Iodine deficiency

Zinc deficiency

Beriberi

Folate (Vitamin B9) deficiency

Niacin (Vitamin B3) deficiency

Vitamin B12 deficiency

Vitamin C deficiency

Wernicke-Korsakoff syndrome

Fat-soluble vitamin deficiency and toxicity: Pathology review

Water-soluble vitamin deficiency and toxicity: B1-B7: Pathology review

Zinc deficiency and protein-energy malnutrition: Pathology review

Nutritional disorders

Nutrition

Pyruvate dehydrogenase deficiency

Videos

Notes