Nutrition Module Diseases and Deficiencies

Lactose Intolerance

• Cause by lactase deficiency, leading to an abnormal accumulation of lactose in the colon

• Bloating, diarrhea, dehydration

Blood Glucose Ranges

Normal:

• FPG: <100 mg/dl

• HbA1c: <5.7%

• OGTT: <140 mg/dl

Prediabetes

• FPG: 100 mg/dl to 125 mg/dl

• HbA1c: 5.7% to 6.4%

• OGTT: 140 mg/dl to 199 mg/dl

Diabetic

• FPG: 126 mg/dl+

• HbA1c: 6.5%+

• OGTT: 200mg/dl+

Type Ia/O Von Gierke Disease

Glucose 6-Phosphatase deficiency

• Mostly affects liver

Type II Pompe Disease

Lysosomal a(1,4) glucosidase deficiency - causes buildup in lysosome

Type III Cori Disease

4,4 Transferase OR 1,6 Glucosidase defiency

• Mostly affects Liver

Type V McCardle Disease

Glycogen phosphorylase deficiency - can’t cleave a(1,4) to release G1P

• Occurs in muscle

Type VI Hers Disease

Glycogen phosphorylase deficiency - can’t cleave a(1,4) to release G1P

• Occurs in the liver

G6PD Deficiency

Glucose 6-Phosphate Dehydrogenase deficiency

• most severe in RBC = will reduce oxidized glutathione = hemolysis caused by ROS

Hemolytic Anemia

Pyruvate Kinase deficiency

• Due to reduced ATP production in RBC’s:

  • Maintenance of ion transporters lost = lose membrane integrity and cell shape

  • RBC’s will lyse or cleared by macrophages

Essential Fructosuria

Fructokinase deficiency

• Fructose accumulates in urine

  • Rare and benign genetic disorder

Hereditary Fructose Intolerance (HFI)

Aldolase B deficiency

• Fructose and Fructose 1-P accumulates in the liver

  • Causes hypoglycemia due to inhibition of GNG

Nonclassical Galactosemia

Galactokinase (GALK) deficiency (rare)

Classical Galactosemia

Galatose-1-Phosphate Uridylytransferase (GALT) deficiency

• Accumulation of galactose-1-phosphate in tissues

• Appearance of galactose in blood and urine

Hypoglycemia

Blood glucose below 40mg/dL risk of coma (lower blood glucose = brain dead)

Alcohol Related Hypoglycemia

Inhibition of GNG due to limited NAD+

Insulin Induced Hypoglycemia

Diabetics receiving insulin treatment might drop BG too far

Postprandial (Reactive Hypoglycemia)

Exaggerated relaese of insulin after a meal (non-diabetic, but possibly pre-diabetic?)

Fasting Hypoglycemia

Reduction in glucose production by gluconeogenesis or glycogenolysis (non-diabetic, caused by medication, traumas, liver illnesses, impaired beta-ox)

Congenital Lactic Acidosis

PDH Deficiency

• Brain - sensitive to acidosis (dependent on TCA to generate energy)

• Variable symptoms

• Neonatal death

Arsenic Poisoning

Inhibits lipoic acid - causes buildup of pyruvate and lactate

• Can cause serious effects of the neurologic, respiratory, hematologic, cardiovascular, GI and other systems

• Death

Beri Beri/Wernicke-Korsakoff'‘s Syndrome

B1 Nutritional Deficiency (WK is associated with chronic alcoholism)

• Edema, anorexia, weight loss, confusion apathy

Scurvy

Vitamin C deficiency

• Defective collagen synthesis (Vit C is cofactor for hydroxylation, will affect prolyl hydroxylase and lysyl hydroxylase)

• Gum ulcers, hemorrhaging

Pellagra

Niacin-Tryptophan deficiency

• 3 D’s: dermatitis, diarrhea, dementia [death]

Megaloblastic anemia due to folic acid deficiency

• Neural tube defects (in developing embryo of pregnant woman), impaired cell division and growth

• Thymidine triphosphate is impaired = RNA and protein synthesis is less pronounced = abnormally large erythroid precursors and RBCs

Megaloblastic anemia due to B12 deficiency

• Neurologic symptoms

• Thymidine triphosphate is impaired = RNA and protein synthesis is less pronounced = abnormally large erythroid precursors and RBCs

Osteogenesis Imperfecta

Mutations of Gly to bulky residue OR null mutations in COL1A1 or COL1A2

• Brittle bones due to defective synthesis of collagen type 1

• Autosomal dominant due to dominant negative effect

Ehlers Danlos Syndromes

Classic (AD): Type V, type I; Vascular (AD): Collagen Type III will cause vascular hemorrhage

• Hereditary connective tissue disorders, autosomal dominant or recessive

• Signs and symptoms: Joint hypermobility, skin hyperextensibility, pain, tissue fragility

Copper Deficiency

• Acquired: High intake of Zn inhibits Cu uptake, Digestive disorders

• Hereditary: Menkes: Copper transporter deficiency

Lipid Malabsorption

Caused by:

• Reduction in bile and pancreatic enzyme secretion

• Defective intestinal mucosal cells

• Steatorrhea (increase lipids in stool)

Treat with short- and medium- chain FAs

CPT-1 Deficiency

Affects liver, impaired GNG = Hypoglycemia, coma, death

CPT-2 Deficiency

Affects muscle (liver, heart) = weakness/cardiomyopathy (common)

Maple Syrup Urine Disease

Branched chain a-keto acid dehydrogenase deficiency

• Burnt sugar odor in urine from byproducts of BCAA = ketoacidosis

• Neurological problems (seizures due to leucine)

  • Treat with diet low in BCAA’s, supplement B1

Methylmalonic Aciduria (MMA)

Methylmalonyl-CoA mutase - cannot process isoleucine, valine, threnione, methionine

• Accumulation of methylmalonate and propionic acid

• Developmental problems, mut⁰ symptoms present at birth

  • Supplement B₁₂

Cb1 (A-G) MMA

Enzymes in Vitamin B₁₂ processing or absorption (adenosyl-cobalamin)

• Accumulation of methylmalonate and propionic acid

• Symptoms present in older infants or children

  • Accompanied by homocystinuria, causing myopathy and thrombosis

• Supplement B₁₂

Alkaptonuria

Homogentisate oxidase - errors in aromatic AA

• Accumulation of homogentistic acid in urine, cartilage and joints (darkens upon oxidation)

• Urine turns dark on exposure to light, degenerative arthritis

  • Treat with diet low in Phe and Tyr

Classic PKU

Phenyalanine Hydroxylase deficiency

• Accumulation of Phe and other neurotoxic byproducts, phenylacids

• Musty urine odor from phenyl acetic acid, mental retardation if not treated

  • Treat with Phe-restricted diet, supplement Tyr

“Malignant” PKU

Dihydropterin reductase deficiency (MORE SEVERE)

• Accumulation of Phe and other neurotoxic byproducts, phenylacids

• Restricted Phe will NOT resolve symptoms

• Supplement products and BH₄

Albinism (Classic)

Tyrosine Hydroxylase deficiency

• Lack of pigmentation, vision defects, increased risk of skin cancer

Cystic Fibrosis

Cl^- ion channel defect (AR)

• Pancreas, lungs, intestines, vas deferens, sweat glands = Imbalance of NaCl = thick mucous

• Main cause of pancreatitis, malabsorption, steatorrhia

Cystinuria

Defect in transport of cystine and basic amino acids

• Malabsorption from gut and kidney

  • Renal colic, kidney stones

Hartnup Disease

Defect in transport of neutral amino acids (leucine, phenyalanine, tryptophan)

• Hyperaminoaciduria, pellagra

Pernicious Anemia

Deficiency in intrinsic factor for absorption of B₁₂

Marasmus

Overall caloric and protein malnutrition in children

Kwashiorkor

Dietary protein deficiency but caloric intake adequate in children

• Will affect proteins produced within body

  • Hepatomegaly - ApoB100

  • PItting edema - Albumin

  • Pot belly

Cachexia

Secondary malnutrition - in cancer patients and the aged due to increased resting energy expenditure

Urea Cycle Disorders

elevated NH₃, elevated blood glutamine, reduced BUN

• Infant normal at birth but fails to thrive

• defects in CPS-I, OTC (X-linked, will also have elevated orotic acid), AS or AL (elevated cirtulline): severe hyperammonemia leads to mental retardation and death

• defect in arginase rare

• defect in NAG will also cause disorder

Severe Combined Immune Deficiency (SCID)

ADA Deficiency - purine degradation, cannot fight off infection

PNP deficiency causes partial immune deficiency - T-cell function

Gout

Overproduction of purines or underexcretion of uric acid, caused by:

• Glucose-6-phosphatase deficiency - increased R5P

• PRPP synthetase - loss of feedback inhibition, increased affinity of R5P

• HGPRT (Lesch Nyhan, X-linked) - inability to salvage guanine and hypoxanthine

Orotic Aciduria

with Hyperammonemia

• No megaloblastic anemia

• Decrease OTC

with Megaloblastic anemia

• No hyperammonemia

• Decrease UMP synthase

Folate/B12 - has megaloblastic but no orotic aciduria

CPS 1 - hyperammonemia but no orotic aciduria