Metabolic Disorders

1
Metabolic Disorders

• CHEM 4203
• Fall 2008

2
CPS I Deficiency
3
What is carbamoyl Phosphate Synthetase I?

• Enzyme found in the mitochondrial matrix of liver
  cells.
• Catalyzes the formation of Carbamoyl Phosphate
  from ammonia, Carbon dioxide, and two molecules
  of ATP.
• Important nitrogen acquiring reaction.
• Important point of regulation in the urea cycle.

4

Carbamoyl phosphate is combined with Ornithine to
form Citrulline, the first step in the Urea cycle.
5
Nitrogen is ultimately removed from the body as
Urea.
6
Effect of CPSI Deficiency

• A deficiency of the CPS I enzyme leads to a build
  up of ammonia in the liver.
• A build up of ammonia in the body can have severe
  effects such as lethargy, convulsions, and early
  death.
• It is a relatively rare disorder but it is hard
  to know the exact number of cases.

7
Treatment

• The initial treatment to reducing the levels
  ammonia is to reduce protein intake, and also
  possible administration of glucose and lipid
  injections.
• If ammonia levels are high dialysis may be
  necessary to remove the excess.

8
Tyrosinemia
John Thompson

• A Genetic Disorder

9
Pathology

• Unable to metabolize tyrosine
• Results in abnormally high levels of tyrosine
  (hypertyrosinemia)
• Three different enzymes can cause three different
  pathological states

10
Type 1 Tyrosinemia

• Most severe case
• Shortage of enzyme fumaryloacetate hydrolase
• Symptoms
• Failure to grow at normal rate
• Bleeding
• Diarrhea
• Vomiting
• Jaundice
• Can lead to liver and kidney failure

11
Type 2 Tyrosinemia

• Shortage of tyrosine aminotransferase
• Symptoms
• Tearing
• Photophobia
• Skin lesions

12
Type 3 Tyrosinemia

• Most rare case
• Shortage of 4-hydroxyphenylpyruvate dioxygenase
• Symptoms
• Mild mental retardation
• Seizures
• Ataxia

13
Treatment

• Low protein diet
• Liver transplant (type 1)
• Nitisinone (type 1)

14
Albinism

• Tam Tran
• CHEM 4203
• November 11, 2008

15
Albinism

• A genetic disorder in which pigment melanin,
  which gives color to eyes, hair, and skin, is
  insufficiently produced or completely not
  produced.
• Occurs in many types of animals.
• In humans, there is one albino in every 17,000
  people.
• There are about 18,000 people affected by
  Albinism in the United States.

16
Symptoms

• Red eyes.
• Pale skin.
• White or pink hair.

(A)
(B)
(C)
17
Effects

• Impaired vision due to insufficient amount of
  pigment.
• Sensitive skin which is easily damaged by sun
  light. Cancer if not protected.
• Minor difficulties in blood clotting and hearing
  sometimes.
• Normal growth and development in humans.

18
Causes

• Mutation of tyrosinase gene in melanocytes.

(D)
19
Causes

• Mutation of tyrosinase gene in melanocytes.

(D)
20
Treatment and Prevention

• No treatment for albinism.
• Relieve symptoms caused by albinism.
• UV sunglasses to protect eyes.
• Sunscreens and clothes to prevent
  sunburn.
• Genetic counseling if albinism
• existed in family history.

21
References

• Pictures
• (A) http//www.righthealth.com/Health/Human_Albi
  no_Pictures/-od-images_5-s
• (B) http//www.kellymilnerhalls.com/content
  /blogcategory/118/68/
• (C) http//www.greenexpander.com/2007/12/04
  /animal-photo-set-5-albino-animals/
• (D) http//albinism.med.umn.edu/factpath.gi
  f
• Sources
• International Albinism Center at the University
  of Minnesota. Facts about Albinism.
  http//albinism.med.umn.edu/facts.htm. accessed
  2008 November 11
• Medical Center at University of Maryland.
  Albinism. 5 February 2008. http//www.umm.edu/en
  cy/article/001479.htm. accessed 2008 November
  11

22
Galactosemia

• Tam Han

23
Galactose Metabolism Disorder

• Affects an individuals ability to properly
  metabolize galactose.
• Defective in the conversion of galactose to
  glucose 1-phosphate.
• Galactokinase
• UDP-glucose 4-epimerase
• Galactose 1-phosphate uridylyltransferase
• Metabolic processes
• Further metabolism of galactose
• Glycolysis

24

• Symptoms and effects
• Galactose 1-phosphate uridylyltransferase
  galactosemia (classic galactosemia)
• Galactokinase deficiency (galactosemia type 2 or
  GALK deficiency)
• Galactose epimerase deficiency
• Common?
• Rare disorder
• Relatively small gene pool
• Treatment
• Strict removal of lactose and galactose from diet

25
References

• Lehninger. Principles of Biochemistry, 4th
  edition. pp. 536-37.
• http//en.wikipedia.org/wiki/Galactosemia
• http//en.wikipedia.org/wiki/Classic_galactosemia
• http//en.wikipedia.org/wiki/Galactokinase_deficie
  ncy
• http//en.wikipedia.org/wiki/Galactose_epimerase_d
  eficiency

26
Maple Syrup Urine Disease

• Jason ONeal
• Chem. 4203
• Dr. Clower

27
What is it?

• Genetic Disorder
• Autosomal recessive metabolic disorder

28
What process is Disrupted?

• The genetic defect causes a deficiency of
  branched-chain Alpha-keto acid dehydrogenase
  complex
• Keeps branched chain amino acids from being
  broken down

29
So whats the Problem?

• A build-up of these AAs, leucine, isoleucine,
  and valine, and toxic by-products
• Symptoms and Effects-
• Urine smells like maple syrup
• Vomiting, feeding difficulties, avoiding food,
  coma, lethargy
• Infants may suffer from brain damage and
  developmental problems
• If untreated die within first months of life

30
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31
How common is it?

• It affects 1 out of 120,000 live births
• Treatment-
• Involves a protein-free diet, diet free of
  branched chain amino acids.
• Must remain on this diet to avoid neurological
  damage.

32
References

• http//www.savebabies.org/diseasedescriptions/msud
  .php
• http//www.emedicine.com/PED/topic1368.htm
  emedicine
• http//www.nlm.nih.gov/MEDLINEPLUS/ency/article/00
  0373.htm

33
Addisons Disease Metabolic disorder

• Student Uzochukwu Adabanya
• Instructor Prof. C Clower
• Institution Clayton State University

34
What leads to this disorder?

• Defects with the Adrenal glands (tuberculosis a
  common cause)
• chronic infections especially certain fungal
  infections
• invasion of the adrenal gland by cancer cells
  that have spread from another part of the body
  especially the breast
• Cytomegalovirus (CMV) virus in association with
  AIDS- causes birth defects
• Hemorrhage (bleeding) into the adrenals during
  shock- rare
• surgical removal of both adrenals
• other associated glands such as the thyroid and
  parathyroid glands could also be defective as in
  polyendocrine deficiency syndrome (PDS)
• All these Lead to adrenal glands not producing
  enough endogenous steroid hormones- mainly
  cortisol and aldosterone in some cases.

35
What leads to this disorder?

• Cortisol- very important glucocorticoid
• Regulated by the hypothalamus and the pituitary
  gland
• maintains blood pressure and cardiovascular
  function
• slows the inflammatory response of the immune
  system
• balances the effects of insulin in breaking down
  sugar for energy
• helps regulate the metabolism of proteins,
  carbohydrates, and fats
• helps maintain proper arousal and sense of
  well-being
• Glucocorticoids are distinguished from
  mineralocorticoids and sex steroids by their
  specific receptors, target cells, and effects

36
What leads to this disorder?

• Aldosterone- also important
• Minerocorticoid- hormones helping with salt and
  water balance
• helps maintain blood pressure
• Helps with water and salt balance in the body by
  helping the kidney retain sodium and excrete
  potassium
• Low levels of aldosterone lead to low blood
  volume and low blood pressure due to loss of
  regulatory function of the hormone

37
Signs and Symptoms

• weight loss
• muscle weakness
• Fatigue
• low blood pressure
• darkening of the skin in both exposed and
  nonexposed parts of the body in certain instances
• marked cravings for salt or salty foods due to
  the urinary losses of sodium
• addisonian crisis- extreme cases

38
Do you think it is common?

• Very rare
• Develops in both men and women of all ages
• Occurs in about 4 in every 100,000 people

39
Treatment

• involves replacing or substituting the deficient
  hormones made by the adrenal glands
• Standard therapy which involves the intravenous
  injections of substances such as hydrocortisone,
  saline (salt water), and dextrose (sugar). rapid
  improvement is commonly noticed
• oral doses of fludrocortisone acetate in
  situations where aldosterone concentration is low
• Surgery
• Patients with chronic adrenal insufficiency might
  need surgery in extreme or critical situations.
  This could be done by administering injections of
  hydrocortisone and saline for general anesthesia.
  

40
References

• http//endocrine.niddk.nih.gov/pubs/addison/addiso
  n.htmtreatment
• http//www.nadf.us/diseases/addisons.htm

41
REFSUMS DISEASE
Sigvald Bernhard Refsum

• By Tamtony H. Nguyen
• Biochemistry 4203

42
CONDITION

• Occurs during lipid metabolism a-oxidation of
  Phytanic-Acid in the liver.
• Metabolic disruption is due to faulty enzyme
• -Phytanoyl-CoA hydroxylase
• Causes excess buildup of Phytol (Phytanic-Acid)
  in the body plasma and tissue
• Very rare and an inherited disorder
• Leads to Neurological defects
• where Myelin Sheath of neurons are damaged

43
SYMPTOMS

• Neurologic damage
• Cerebellar degeneration
• Peripheral neuropathy(weakness Nausea)
• Blindness
• Ataxia
• Scaly skin
• Difficulty hearing
• Cataracts
• Epiphyseal dysplasia
• Loss of smell

44
PREVENTION AND TREATMENT

• Primary prevention for this disorder is a
  restrictive diet avoiding dairy products, beef,
  lamb, and fatty fish.
• Plasmapheresis- Filtering Blood for removal of
  Phytonic Acid (plasma exchange).

http//www.londonhospitals.ca/successes/renal.htm
45
REFERENCES

• A.J. Wills, N.J. Manning and M.M. Reilly
  Refsum's disease. Q J Med 2001 94 403-406
• "Health Minister Opens New Dialysis/Plasmapheresis
  Unit at Victoria Campus." London Health Science
  Centre. 23 Mar. 2001. St. Joseph's Healthcare
  London. 11 Nov. 2008 lthttp//www.londonhospitals.c
  a/successes/renal.htmgt.
• "NINDS Refsum Disease Information Page." National
  Institute of Neurological Disorder and Stroke. 14
  Feb. 2007. 6 Nov. 2008 lthttp//www.ninds.nih.gov/d
  isorders/refsum /refsum.htmgt.
• "Refsum Disease." 1 Aug. 2008. United
  Leukodystrophy Foundation. 6 Nov. 2008
  lthttp//www.ulf.org/types/refsum.htmlgt.
• "Refsum's disease." Wikipedia. 6 Nov. 2008
  lthttp//en.wikipedia.org/wiki/refsum27s_diseasegt.

46
Lesch-Nyhan Syndrome

• Salwa Qadri

47
What is it?

• Genetic disorder
• X-linked recessive disease
• Rare
• Deficiency of the enzyme hypoxanthine-guanine
  phosphoribosyltransferase (HPRT).

48
Metabolic process of HPRT

• Functions in recycling of purine bases
  hypoxanthine and guanine
• No salvage in absence of HPRT
• Speeds up synthesis of purines
• Failure of recycling process increased
  synthesis of purine overproduction of uric acid

49
Symptoms Effects

• Severe gout, poor muscle control, and moderate
  retardation, which appear in the first year of
  life. 
• Neurological symptoms include facial grimacing,
  involuntary writhing, and repetitive movements of
  the arms and legs
• Self-mutilating behaviors characterized by lip
  and finger biting that begin in the second year
  of life.

50
Treatment

• Symptomatic
• Gout treated with allopurinol
• Kidney stones may be treated with lithotripsy
• No standard treatment for the neurological
  symptoms of LNS. 
• Death usually due to renal failure

51
Methylmalonic Acidemia

• Biochemistry II
• Kelly Ta

52
Methylmalonic Acidemia

• an inherited disorder - gene defect is an
  autosomal recessive genetic trait.
• the body is unable to process certain proteins
  and lipids properly.
• caused by an enzymatic defect in the oxidation of
  certain amino acids and lipids.
• Mutation in the genes that coded for
  Methylmalonyl CoA mutase, the enzyme works with
  vitamin B12 to break down several amino acids,
  certain lipids, and cholesterol.

53
Methylmalonic Acidemia

• This condition occurs in an estimated 1 in 50,000
  to 100,000 people.
• Symptoms usually appear in early infancy and vary
  from mild to life-threatening.
• Vomiting, dehydration, weak muscle tone,
  excessive tiredness, and failure to gain weight
  and grow at the expected rate.
• Long-term effects include feeding problems,
  mental retardation, chronic kidney disease.

54
Methylmalonic Acidemia

• Without treatment, this disorder can lead to coma
  and death in some cases.
• Treatment includes a carefully controlled diet,
  including a low-protein and/or restriction of
  isoleucine, valine, and threonine.
• Medical food supplementation may be needed as
  well.

55
Wolmans Disease

• Background
• Autosomal Recessive (Rare)
• Lipid storage Disease
• Acid Lipase deficiency? Lipid accumulation
• -Mutation in LIPA Gene

56
Symptoms
Hepatosplenomegaly
Hypotonia (low muscle tone)
Umbilical Hernia
Red blood cell
57
Diganosis

• gt 10 lysosomal Acid lipase
• - Skin cell
• - Blood
• Amiocentesis

58
References

• 1. National Institute of Neurological Disorder
  and stroke.
• NNDS Acid Lipase Disease Information Page.
• http//www.ninds.nih.gov/disorders/acid_lipase/ac
  id_lipase.htm.
• 2. W Krivit, Peter C et al 2000. Wolman disease
  successful treated by bone marrow
  transplantation.
• Bone Marrow transplantation. 567-70.
• 3. Images
• www.nlm.nih.gov/.../ency/fullsize/17215.jpg
• fig.cox.miami.edu/Faculty/Dana/amniocentesis.jpg.
  
• ghr.nlm.nih.gov/dynamicImages/chromomap/lipa.jpeg
  

59
Tay-Sachs diseases

• What is it?
• What is the defective process?
• Metabolic processes
• Symptoms and Effects
• How common is it?
• Can it be treated?

60
What is Tay-Sachs disease?

• Inherited sickness caused by a build up of
  dangerous fat molecules. (brain and nerve
  tissue).
• Ganglioside GM2
• Defective process
• Gene location chromosome 15
• Responsible for the production of an enzyme
  (Hex-A)
• Cause Insuficient activity of enzyme
• Beta hexoaminidase (Hex-A)

61
Metabolic process
62
Symptoms and effects

• Children look normal up to six months
• Regression in development
• At two years old repeated seizures, inability
  to crawl or roll over
• At four Years old Children nervous system
  affected resulting in death.

63
How common is Tay-sachs disease

• Commonality of Tay-Sachs disease
• Common in Eastern Europe
• People of Ashkenzani
• People of Jewish descent
• U.S (1/27) Jewish are affected
• Can Tay-Sachs disease be treated ?
• No treatment for Tay-Sachs disease
• Methods tried to cure Tay-Sachs disease
• Enzyme hexoaminidase replacement
• Area of research Gene Therapy

64
Ressources

• Principles of Biochemistry, 4th ed. (David L.
  Nelson, Michael M. Cox
• Concepts of Genetics, 8th ed. (Klug, Cumming,
  Spencer).
• Genome.gov

65
HOMOCYSTINURIA
NGOC TRAN Biochemistry Dr. Clower
66
What is it?

• Cystathionine beta synthase deficiency
• Inherited Disorder
• The body can not break down methionine in food

67
Defective Process

• CBS Cystathionine Beta-Synthase Gene (control)
• Cystathionine Beta Synthase Enzyme
• Changes homocysteine to other compounds needed
  for the body
• Alteration to CBS gene- CBS enzyme goes down,
  homocystine builds up in the blood stream.
• Organs and tissues, including the eyes and the
  skeletal, vascular and central nervous systems

68
Metabolic Process
www.ncbi.nlm.nih.gov/bookshelf/picrender.fcgi
69
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70
What are the symptoms and effects?

• Visual problems
• Scoliosis
• Seizures
• Abnormal thinning
• Mental retardation
• Etc.

71
Common?

• 1 out of 335,000 people
• worldwide

72
TREAMENTS ?

• No specific cure for homocystinuria.
• Medication/Diet
• Vitamin B6- reduce blood clotting eye bone
  problems

73
THANK YOU
74
Sitosterolemia

• Theresa Sihaphonh

75
Sitosterolemia

• Sitosterolemia is inherited as a rare autosomal
  recessive disorder that leads to the
  hyperabsorption and decreased excretion of plant
  sterols
• Mutation in ATP-binding cassette transporter (ABC
  transporter) proteins
• Plant sterols are not utilized by mammalian
  cells fewer than 5 are absorbed from GI tract
  and the rest is excreted by the liver
• The sterols that do enter intestinal cells are
  pumped back out by ABC transporter proteins
• Mutation less hepatic secretion less
  excretion in the liver accumulation in cells

76
Sitosterolemia

• Reduced whole-body cholesterol biosynthesis
• Reduced HMG-CoA reductase activity rate-limiting
  enzyme in cholesterol biosynthesis
• Increased LDL levels
• Symptoms tendon xanthomas premature
  atherosclerosis
• Rare disorder only 45 cases worldwide
• Treatment strict diet reducing intake of foods
  rich in plant sterols (vegetable oil, olives,
  avocados)

77
Zellweger Syndrome

• By Hardik Modi

78
What is it Zellweger Syndrome?

• It is one of the 4 perioxisome biogenesis
  disorders (PBD)
• Patients lack perioxisome
• It is an inherited disorder

79
What are the defective processes?

• Defects in genes that are active in brain
  development and myelination
• Elimination of perioxisomes
• Lack of Perioxisomes causes lack of enzymes used
  in Beta-oxidation of fatty acids

80
Beta oxidation will not occur
81
Symptoms and Effects

• Facial deformities
• High forehead, underdeveloped eyebrows, deformed
  ear lobes.
• Neurological abnormalities
• Mental retardation and seizures
• Enlarged liver, Jaundice, gastrointenstinal
  bleeding.
• Low muscle tone

82
How common is it? What are the Treatments?

• 1 of every 50,000 to 100,000 births
• Affects males and females equally
• It occurs at birth
• No treatments are available

83
References

• http//en.wikipedia.org/wiki/Zellweger_syndrome
• http//www.ninds.nih.gov/disorders/zellweger/zellw
  eger.htm
• http//rarediseases.about.com/od/rarediseasesz/a/0
  30505.htm

84
Porphyrias
http//www.medmemoweb.com/Porphyria-cutanea-tarda.
rea.gif

• CHEM 4203
• Alysia Giani

85
What is it?

• Group of disorders
• Enzymes in Heme biosynthetic pathway
• 8 Enzymes
• Affects skin (cutaneous), nervous system (Acute),
  or Both.
• Hereditary coproporphyria
• Variegate porphyria
• Acquired or Inherited
• Porphyria cutanea tarda

http//www.blc.arizona.edu/courses/bioc462b/grimes
/nitrogen06/ch22/box-22-01.jpg
86
Symptoms

• Three Major Symptoms
• Abdominal Pain
• Photodermatitis
• Problems with nervous and muscular systems
• Muscle pain/ weakness
• Personality changes
• Numbness/ Tingling
• Prevalence
• 1 in 500 to 50,000
• 1 to 2 in 100,000 (PCT)
• 3 in 1,000 (VP)- Whites in S. Africa

http//medimages.healthopedia.com/large/skin-porph
yria.jpg
http//hjk880524.tripod.com/sitebuildercontent/sit
ebuilderpictures/phophyria.jpg
87
Treatment

• Tests
• Urine
• PROTO blood test
• Treatment
• Hematin IV
• Pain medication
• Sedatives
• Propranolol
• Others
• Beta-Carotene supplement
• Removal of blood
• Higher carbohydrate intake

88
Interesting Facts

• Vampires
• Porphyrias Cutanea Tarda

http//www.hrp.org.uk/Images/George20III_Copyrigh
t20Historic20Royal20Palaces2003.jpg

• King George III
• - Variegate Porphyrias

89
References

• http//digestive.niddk.nih.gov/ddiseases/pubs/porp
  hyria/index.htm
• http//www.ghr.nlm.nih.gov/conditionporphyria
• http//www.nlm.nih.gov/medlineplus/ency/article/00
  1208.htm
• http//www.porphyriafoundation.com/about_por/histo
  ry.html

90
Argininosuccinic Acidemia

• Urea Cycle disorder
• Victims of this disease can not convert ammonia
  into urea to be excreted from the body.

91
http//j2k.naver.com/j2k.php/japan/www.answers.com
/topic/argininosuccinic-aciduria

• Argininosuccinate created in the urea cycle is
  missing the enzyme argininosuccinase
  (argininosuccinic lyase)to cleave it.

http//www.carolguze.com/text/442-11-clinical_gene
tics.shtml
92

• Symptoms
• Lack of appetite, vomiting, restlessness,
  seizures, brain damage, coma and death.
• Treatment
• Low protein diets, arginine supplementaion and in
  some cases dialysis.
• Frequency
• 1 of every 70,000 live births will have some form
  of ASA.

93

• "Amino Acid Disorders." www.newbornscreening.info
  September 31, 2006 1-11. 11 Nov 2008
  lthttp//www.newbornscreening.info/Parents/aminoaci
  ddisorders/ASAL.pdfgt.
• "Argininosuccinic aciduria." Genetics Home
  Reference Mar 2007 09 Nov 2008 lthttp//ghr.nlm.nih
  .gov/conditionargininosuccinicaciduriagt.

94
Nonketotic Hyperglycinemia

• Monique M. Nurse
• Biochemistry
• 11/11/08

95
Nonketotic Hyperglycinemia (NKH)

• aka glycine encephalopathy
• Autosomal recessive hereditary metabolic disorder
• affects the breakdown of the amino acid glycine
  in infants
• Characterized by abnormally high levels of the
  amino acid glycine in the blood, urine, and the
  cerebrospinal fluid.
• cause extensive neuronal damage in neonatal brain
• via N-methyl-D-aspartate glutamate
  receptor-mediated

96
Where does it occur?

• Glycine Cleavage System (GCS)
• a multi-enzyme complex composed of four different
  protein components
• P-protein (glycine dehydrogenase),
• T-protein (catalyses a methyl group to
  tetrahydrofolate),
• H-protein (aminomethyl carrier)
• L-protein (normal)
• Mutations in P-, T-, and H-proteins are
  responsible for nonketotic hyperglycinemia.

97
What is affected?

• Glycine Cleavage System
• mutation in the GCS
• inadequate supply of the enzymes necessary to the
  break down of glycine causing a build up of
  glycine in the body.
• The AMT and GLDC genes

Fig. infant brain with NKH
98
Symptoms and Effects

• Four forms of this disorder
• Neonatal form
• seen in the first few days after birth
• low muscle tone (hypotonia), and drowsiness
• seizures and mental retardation
• Infantile form
• six months of seemingly normal development
• with the exception of occasional feeding
  difficulties seizures
• varying degrees of mental retardation become
  evident.

99
Symptoms and Effects CONT.

• Mild-episodic form
• appears during childhood episodes of delirium
  involuntary, jerky movements (chorea) inability
  to look upward (vertical gaze palsy)
• fever and mild mental retardation
• Late-onset form
• during childhood with progressive stiffness in
  both legs and degeneration of the optic nerve,
  leading to loss of sight.
• Neither seizures nor mental retardation are
  associated

100
How common is NKH?

• Rare metabolic disorder that usually affects
  infants soon after birth.
• Estimated 1 in 60,000
• Males females appear to be affected in equal
  proportions.
• Both parents are carriers
• 25 chance child will be born with the disease
• 50 chance child will be a carrier for the gene
  defect.

101
Can it be treated? How?

• At this time there are no existing treatments.
• Rarely children grow out of NKH and go on to live
  normal lives.
• For some individuals glycine levels have
  decreased but mental retardation and seizures may
  still persist.

102
Taruis Disease
103
Taruis Disease

• Gylcogen storage disease
• Phosphofructokinase deficiency
• Glycolysis
• Glyconeogenesis metabolism slows
• Glycogen buildup

104
Taruis Disease

• Organ Affected
• Erythrocytes
• Muscles
• Symptoms
• Exercise-induced fatigue
• Muscle Pain
• Hemolytic Anemia
• Myoglobin in urin
• Jaundice

105
Taruis Disease

• Affects 2.3 children per 100,000 births per year
• Disease present itself during early childhood
• Inherited autosomal recessive condition
• Appears to be prevalent among people of Ashkenazi
  Jewish decent

106
Taruis Disease

• No Treatment or Cure
• Diet Management
• High Fat Content
• May not be effective
• Liver Transplantation
• Abolish biochemical abnormalities

107
References

• Anderson, W. E. (2007). Glycogen Storage Disease,
  Type VII. Retrieved November 10, 2008, from
  http//www.emedicine.com/med/topic913.htm.
• Mallery, C. PFK-1. Retrieved November 10, 2008,
  from http//porpax.bio.miami.edu/cmallery/255/255
  atp/mcb8.12.PFK.jpg
• Nelson, D. L., Cox, M. M. (2008). Principles of
  Biochemistry. New York W. H. Freeman and
  Company.

108
Favism

• A condition caused by accumulation of hydrogen
  peroxide and hemolytic anemia
• - destruction of red blood cells

109
Symptoms

• Fever
• Nausea
• Abnormal pain and headaches
• Anemic conditions
• Pallor
• - reduced a mount of oxyhemoglobin on skin.

110
Causes of Favism

• Exposure to pollen of fava plants
• Eating fava beans
• Deficiency of Glucose-6-Phosphate Dehydrogenase
• It is common around countries in the Middle East
  and Mediterranean

111
Fava Beans

• Glycosides vicine and
• Convicine
• - depletion of Glutathione
• main commercial source
• of the drug L-dopa
• - converted to dopamine in the brain
• L-dopa is found in food and made from tyrosine in
  humans

112
G6PD

• Glucose-6-phosphate dehydrogenase
• Involved in the pentose phosphate pathway.
• Supplies cells such as RBCs with energy by
  maintaining the level of NADPH
• NADPH regulates the amount of glutathione because
  the tripeptide protects red blood cells from
  oxidative damage.
• - regulation of peroxide accumulation

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Who is at risk?

• Deficiency of the enzyme glucose-6 phosphate
  dehydrogenase is an X-linked genetic trait.
• Men versus women
• Breastfeeding infants
• Treatment involved blood transfusion

114
Sources

• www.adam.com
• Principles of Biochemistry by Lehninger, Nelson,
  and Cox, 4th ed. (2005) or 5th ed. (2008), W. H.
  Freeman and Co.

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Phenylketonuria

• By Laurie Brier

116
What is PKU?

• Phenylketonuria (PKU)
• Autosomal recessive
• Normal catabolism of phenylalanine ?
• Defective phenylalanine hydroxylase (PAH)

117
What happens when PAH does not work?

• Alternative pathway
• High levels of phenylalanine and phenylpyruvate
• Phenylpyruvate is decarboxylized into
  phenylacetate
• Odor

http//www.uic.edu/classes/phar/phar332/Clinical_C
ases/aa20metab20cases/PKU20Cases/PKU20biochem
20intro.htm
118
Other Causes

• Defective dihydrobiopterin reductase
• Regenerates tetrabiopterin
• cofactor of phenylanine hydroxylase
• L-Dopa and 5-HTP

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Symptoms of pku

• Epilepsy and mental retardation
• 10 in 100,000 newborns diagnosed yearly

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There is hope!

• Early detection
• Screen for disease and type
• Treatment
• Low protein diet (PAH)
• L-Dopa and 5-HTP (dihydrobiopterin reductase)

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Alkaptonuria black urine disease

• By Corney Crumbley

122
Alkaptonuria that sounds like a disease

• This disease is and rare autosomal recessive
  condition.
• The disease is due to the inablilty to properly
  metablizing tyrosine
• This allows for the build up for toxic tyrosine
  by product Homogentisic acid.

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Why enzyme Why?

• The enzyme homogentisate 1,2-dioxygenase, which
  is involved in the break down of aromatic rings
  such as tyrosine does not work.
• The metabolic process that is effected is The
  degrading of Tyrosine to Fumarate is effected at
  step three where Homogentisate to 4
  Maleylacetoacetate.

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Where does it Hurt

• Some of the symptoms are sclera of the eyes may
  be pigmented (later age)
• Sweat may turn brown as well as standing urine
  which is noticed in babies
• Kidney stones and stones in the prostate in men
  are common
• The effects are mostly due to Homogentisic acid
  in tissues.
• Once in the joints it can lead to cartilage
  damage mostly in the spine leading to lower back
  pain. Joint a replacement is often necessary at
  young age

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Dude once there is no coming back

• This disease is common in Slovakia and Dominican
  Republic
• Less than 1 in 250000 are effected by this
  disease.
• There is no cures but only treatments
• Restriction of Phenylalanine, tyrosine, vitamin C
• The insecticide nitisinone which serves as an
  inhibitor in the production of Homogentisic acid
  from 4-hydroxyphenylpyurvic acid.

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Thank you