Metabolic Diseases

1. INTRO 2 GENERAL PATH (PATH 210)
G5) Discuss the different types of metabolic
diseases, their pathogenesis, clinical
manifestations and treatment modalities

2. HEALTH
“state of complete
physical, mental, and
social well-being and
not merely absence
of disease / infirmity”
(WHO, n. d).
DISEASE
Harmful deviation from
the normal structural
or function state of an
organism, usually
associated with signs
and symptoms
(Burrows et al, 2022).

3. METABOLISM
chemical and biochemical processes
that sustain life in terms of: growth,
reproduction, damage repair, and
environmental response (Kandola,
2021).
METABOLISM

4. METABOLIC
DISEASE/DIS
ORDER
conditions
that impair
metabolism
(Kandola,
2021). Some
are inherited.
PATHOGENESIS
Mechanism through
which the
`cause`[etiology]
operates to produce
pathological and clinical
manifestations (EPHTI,
2004).

5. CLINICAL
MANIFESTATIONS
Visible signs
and symptoms
of a disease.
TREATMENT
MODALITIES/TECHNIQUES
Methods used for
diagnosis and
treatment of a
disease.

6. DIABETES MELLITUS [DM] ~ by Ouma Winnie
Types
- 1
- 2
- Gestational

7. INTRODUCTION
• DM is a type of metabolic
disease and a polygenic
disorder.
• That is, it has
multifactorial modes of
inheritance.
• Common feature:
hyperglycemia
Classification
• Based on pathogenic
mechanism.
Type 1
• 1A: results from
autoimmune beta cell
destruction leading 2
insulin deficiency
• 1B [idiopathic]: leads to
insulin deficiency &
ketosis.
• NB: Cause of insulin def is

8. DM CLASSIFICATION
not known.
Type 2
• Characterized by insulin
resistance, impaired
insulin production, & (+)
glucose production
Epidemiology
• Type 2 DM accounts for
80% of all cases world-
wide.
• Type 1 accounts for 5-
10% of all cases.
• Age < 60: DM incidence in
men == women.
• Age > 60: DM incidence in
men > women

9. PATHOGENESIS: TYPE 1A
• Begins with genetic
susceptibility & some
environmental factors.
• Autoimmune destruction
of (80%) beta cells of the
pancreas.
• Certain environmental
factors trigger genetic
factors leading to this auto
-immune rxtn.
Genetic factors
involvement
• Some Type 1 diabetics
have parent(s) / sibling(s)
with disease.
• 95% of Type 1 diabetics
express either HLA- DR3

10. PATHOGEN (cont.)
or HLA- DR4, or both.
Environmental Factors
• Viral infection to the
pancreas.
• Exposure to proteins
found in cow’s milk

11. PATHOGENESIS: TYPE 2
• Polygenic disorder
• Majorly caused by: insulin
resistance & abnormal
insulin secretion.
Genetic factors
• 60% have parent(s) or
sibling(s) with disease.
• Type 2 DM has strong
genetic basis than type 1.
• No association with MHC
genes
• Hyperinsulinemia:
increased insulin conc. In
blood in an attempt to
overcome peripheral
insulin resistance.
• However, this only results

12. PATHOGEN (cont.)
in decreased insulin
receptors.
Environmental factors
• Obesity [increases insulin
resistance].
Pathology
[morphology]
• Type 1: low B cell mass,
Lymphocyte infiltration, &
lesions in the pancreases
of children.
• Type 2: amyloid [protein
misfolding & deposition]
deposition esp in older
patients, 60 >

13. CLINICAL MANIFESTATIONS & COMP.
• Polyuria (dilute urination),
polydipsia (thirsty), & polyphagia
(hunger) [with weight loss or
DKA (Diabetic ketoacidosis)].
TREATMNT MODALITIES
• Insulin therapy
• Healthy eating
• Weight loss
• Regular exercise
• Blood sugar monitoring
• Carbohydrate counting

14. GAUCHER’S DISEASE (GD) ~by Catherine Boke
- Type 1
- Type 2
- Type 3

15. INTRODUCTION
• An inherited genetic and
lysosomal storage
disorder.
• Causes build up of fatty
acids in bone marrow,
liver, and spleen.
• These FAs weaken bones
and enlarge organs thus
interfering with their funct.
PATHOGENESIS
• Caused by
glucocerebrosidase, a
lysosomal enzyme
• This enzyme is involved in
fat breakdown, thus lack
of it leads to build up in
bone marrow & brain.

16. CLINICAL MANIFESTATIONS
• Anemia
• Enlarged organs: spleen &
liver
• Clotting problems
• Fatigue
• Lung problems
• Pain: due 2 (-) blood flow
• Bones fracture easily
• Osteonecrosis: lack of O2
• Cognitive difficulties
• Eye problems
Diagnosis
• Genetic analysis
• Blood tests: check for
enzyme levels
• Physical exam: check size
of spleen & liver by
pressing on the abdomen

17. TREATMENT MODALITIES
Treatment for Type 1
• Enzyme replacement
therapy (ERT) – increase
enzyme levels. Given
intravenously
• Substrate reduction
therapy (SRT) – decrease
build up of fatty
chemicals. Given orally.
• No treatment for
neurological damages for
type 2 and 3
Complications
• Delayed growth & puberty
• Weak bones
• Joint & bone pains
• Brain damage
• Anemia

18. MITOCHONDRIAL DISEASE ~by Livingstone Osiemo
A group of disorders caused by dysfunction of
mitochondria.

19. INTRODUCTION
• Causes defects that affect
normal mitochondrial
operation.
• Severity varies from
person to person
• Worse in cells such as
muscle, cerebrum, and
nerves, which use a lot of
energy.
Examples
• Mitochondrial myopathy
• DM & deafness
• Leigh syndrome
Causes
• Mutations in mitochondrial
DNA
• Acquired mitochondrial
dysfunction due 2 adverse

20. Causes (cont.)
Adverse effects of drugs,
infections, or environmental
factors
Clinical Manifestations
• Poor growth
• Muscle weakness
• Vision & hearing issues
• Learning disabilities
• (+) risk of infections
Diagnosis & Treatment
• Southern blot test,
sequencing, metabolic &
neurological exam.
• No specific treatment.
Mitochondrial replacement
therapy is considered a
treatment procedure but
still in research

21. NIEMANN-PICK DISEASE ~ by Rachami Kevin
- Niemann-pick disease is an inherited disease that affects
lipid metabolism or the way fats, lipids and cholesterol are
stored or removed from the body.
- The disease is broken down into types A, B, C, and E.
Types A and B are referred to as type 1; Type C is referred to
as type 2

22. DIAGNOSIS
Types A and B
• Test is done on blood or bone
marrow to measure amount of
ASM [acid sphingomyelinase
enzyme] in white blood cells
Type C
• Usually diagnosed with a skin
biopsy
• Analysis on how skin cells
grow, move & store
cholesterol is done
• ASM enzyme production instructions
are given by SMPD1 gene.
• This is the gene whose mutations
result in type A & B Niemann-Pick
disease
Causes
• Type A & B occur when acid
sphingomyelinase(ASM)is not
properly produced in the white
blood cells
• Type C is caused by the body's
inability to efficiently remove
excess cholesterol and other
lipids

23. CLINICAL MANIFESTATIONS
Type A
• Swelling of the abdomen
• Swollen lymph nodes
• Difficulty feeding
• Poor muscle tone
• Brain damage
• Lung disease
• Frequent respiratory
infections
Type B
• Swelling of the abdomen
• Respiratory infections
• Low blood platelets
• Poor coordination
• Lung problems
Type C
• Difficulty moving limbs;
enlarged spleen; jaundice;
seizures; & tremors.

24. CLINICAL MANIFESTATIONS (cont.)
Type E
• Swelling of spleen
• Neurological problems
TREATMENT
- Type A: There’s no known
treatment for type A
- Type B: Bone marrow
transplant, enzyme replacement
therapy, & gene therapy
- Type C: A medication called
miglustat is currently used to
treat type C

25. HEMOCHROMATOSIS ~ by Samson Palelo
- Type 1: results from mutations in HFE gene
- Type 2: results from mutations in HAMP gene / HJV gene
- Type 3: results from mutations in TFR2 gene
- Type 4: results from mutations in SLC40A1 gene

26. INTRODUCTION
• It’s a condition where the body
takes up and stores more iron
than it needs & stores it in the
liver, pancreas, and heart.
DIAGNOSIS
• Blood tests are ordered to
check 4 gene mutations.
• Presence of 2 copies of HFE
link gene with C282Y mutatn
confirms diagnosis of primary
hemochromatosis
PATHOGENESIS
Main cat. Of pathophysiological
mechanism include:
• (+) absorption of dietary iron in
upper intestine
• Altered funct. Of HFE protein
• Tissue injury & fibrogenesis
induced.

27. CLINICAL MANIFESTATIONS
• Joint & abdomen pains
• Tiredness & weakness
• Darkening skin color
Treatmnt techniques
• Phlebotomy: deplete
excess iron stores
• Chelation therapy: use of
special drugs 2 remove
excess iron from blood.
Complications
• Diabetes [due to damage on
pancreas]
• Liver problems
• Heart problems
• Changes in skin color
• Reproductive problems

28. PHENYLKETONURIA[PKU] ~ by Thomas Machori
- Classical: most severe
- Mild: moderate (phenylalanine levels)
- Mild hyperphenylalanemia: least sever

29. INTRODUCTION
• An inherited disorder which
causes phenylalanine build up
in the body.
• Phenylalanine is a protein
found in artificial sweetners.
• Artificial sweetners such as
aspartame are added to many
medications, diet foods &
sodas.
• Aspartame contains phenylal.
• PKU is an inborn disorder of
phenylal. metabolism.
• It is caused by a change in
phenylal. hdroxylase(PAH)
gene.
• This gene helps create the
enzyme needed to break
down phenyal.
Clinical manifestations:
eczema, hyperactivity,
microcephaly, stunted growth…

30. PATHOGENESIS
• PAH leads to Phenylal. &
metabolites accumulation in in body
tissues.
• Disorder is passed by autosomal
recessive inheritance [copies of
both genes must be mutated for
condition 2 develop]
Complications:
• Irreversible brain damage; seizures;
and tremors
Treatment:
• Diet low in phenylal. (fish, milk,
nuts, chicken)
• Medications (saproprotein
dihychloride)
• Genetic counselling before
pregnancy
Diagnosis
• 1-2 days after birth
• Blood drops taken from
newborn’s heel – blood tests
• Urine tests & genetic testing

31. CONCLUSION
• Other metabolic diseases
include:
- Krabbe disease
- Hunter Syndrome
What do we eat??
. Some metabolic disease
require intake of certain
foods while other MB
discourage intake of these
same foods.
• Remember: an apple a day
keeps the doctor away; and
Prevention is better than cure…

32. Expert Contributors [Prospective MDs &
COs]
• Catherine Boke: HP14/14265/21
• Deisy Leah Akinyi: H14/03922/21
• Rachami Kevin: H14/04791/21
• Samson Palelo: HP14/06108/19
• Thomas Machori: H14/05240/21
• Livingstone Osiemo: H14/04792/21
• Ouma Winnie: HP14/14393/21

33. REFERENCES
• WHO. (n. d). Health and Well-Being.
https://www.who.int/data/gho/data/major-themes/health-and-well-
being#:~:text=The%20WHO%20constitution%20states%3A%20%
22Health,of%20mental%20disorders%20or%20disabilities.
• Burrows, W. and Scarpelli, . Dante G. (2022, August
24). disease. Encyclopedia Britannica.
https://www.britannica.com/science/disease
• Kandola, A. (2021, October 27). What to know about metabolic
disorders. V. Avi (Ed.).
https://www.medicalnewstoday.com/articles/metabolic-disorders
• EPHTI. (2004). General Pathology.
https://www.cartercenter.org/resources/pdfs/health/ephti/library/lec
ture_notes/health_extension_trainees/generalpathology.pdf