Prelims - Galactosemia, PKU, and MSUD

Galactosemia

• body's inability to use galactose as a source of energy.

• abnormal amounts of galactose in the blood

• deficient with liver enzyme GALACTOSE I - PHOSPHATE URIDYLTRANSFERASE (GALT) that converts galactose into glucose.

Diagnostic Evaluation (Galactosemia)

• History taking

• Physical exam

○ Malnutrition

○ Dehydration

○ Decreased muscle mass and body fat

● Galactosuria

● Increased levels of galactose in the blood

Treatment Management (Galactosemia)

• Avoid milk and milk products

• Substitute with lactose-free or Galactose-free milk, such as Soy-based milk

• Galactose restricted diet must be followed for life

Glucose-6-Phosphate

Dehydrogenase Deficiency (G6PD)

• a genetic, X-linked recessive disorder characterized by a deficiency of the G6PD enzyme, which is essential for protecting red blood cells (RBCs) from oxidative damage.

X-Linked Recessive Inheritance of (G6PD)

The X-linked recessive inheritance, where

the affected gene is found on the X

chromosome. Males are more likely to be

affected because they have only one X

chromosome. If the father is affected and

the mother is normal, all daughters

become carriers and all sons are

unaffected. If the mother is a carrier and

the father is normal, some sons may be

affected,

Trigger Factors of G6PD

Kids with G6PD deficiency

typically do not show any

symptoms of the disorder until

their red blood cells are

exposed to certain triggers,

which can be:

illness, such as bacterial

and viral infections

■ certain painkillers and

fever-reducing drugs

like aspirin

■ certain antibiotics (especially those that

have "sulf" in their names like sulfamethoxazole-bactrim)

■ Red wine

■ Vitamin K

■ Soya foods - taho, tokwa, soy sauce

■ antimalarial drugs, especially those that have "quine" in their names like chloroquine)

■ Legumes - munggo, garbanzos, abitsuelas

■ Naphthalene (moth balls); FAVA beans; Blueberries

Clinical Manifestation / Sign or Symptoms (galactosemia)

1. Dark urine

2. Fever

3. Pain in abdomen

4. Enlarged spleen and liver

5. Fatigue

6. Pallor

7. Rapid heart rate

8. Shortness of breath

9. Jaundice

Pathophysiology (Galactosemia

Glucose-6-phosphate dehydrogenase

(G6PD) deficiency in red blood cells makes

them vulnerable to damage when exposed

to certain triggering factors. As a result, the

red blood cells are destroyed prematurely,

leading to hemolytic anemia. This causes

symptoms such as pallor, dizziness,

headache, difficulty of breathing,

palpitations, and tea-colored urine. The

destroyed red blood cells are then broken

down by the liver, producing bilirubin as an

end product.

Lab diagnostic results

Check G6PD levels

● Bilirubin level

● CBC (Hgb) 11

● Check presence of Hgb in the urine

● Haptoglobin level

○ a protein produced by the liver. It attaches to a certain type of hemoglobin in the blood

● Reticulocyte count

● LDH (Lactate dehydrogenase) test

● Methemoglobin reduction test

Phenylketonuria (PKU)

• absence of the enzyme phenylalanine hydroxylase (PAH) - [can be found on chromosome 12] needed to metabolize the essential amino acid phenylalanine

• Excessive accumulation of phenylalanine is neurotoxic in the body

• protein consumed from food (such as fish, cheese, eggs, and meat) and protein derived from muscle breakdown are both converted into amino acids. These amino acids include Phenylalanine (Phe) and various Other amino acids. Phenylalanine is then metabolized by an active enzyme called Phenylalanine Hydroxylase,converting it into Tyrosine.

Pathophysiology (PKU)

• begins with the intake of Dietary Phenylalanine, but the Normal metabolic pathway is blocked. This initial block leads to two main consequences:

○ Increased serum levels of phenylalanine and Decreased tyrosine production.

• The decrease in Tyrosine has several secondary effects,

○ Decreased dopa,

○ Decreased melanin

○ Decreased tryptophan

Clinical Manifestation (PKU)

• intellectual disabilities

● behavior problems

● hyperactivity

● restlessness or irritability

● seizures

● a skin condition called eczema

● a "musty" or "mousy" body odor

● fair hair and skin

Diagnostic Evaluation (PKU)

Guthrie bacterial inhibition assay

● Checks phenylalanine levels in the

blood

● Presence of bacillus subtilis

(excessive amounts of

phenylalanine)

○ Normal range (newborns): 0.5

- 1 mg/di

○ Normal value: 1.6 mg/dl

Treatment Management (PKU)

• The Management of PKU centers on

strict protein diet restriction for the

patient's entire life.

○ This crucial intervention should start as soon as possible but not later than 7 – 10 days after birth to prevent irreversible brain damage.

● The diet relies heavily on Phenyl-Free Foods and encourages choosing foods closest to the "Bull's-Eye," favoring items like low-protein breads and pastas, fruits, vegetables, and potatoes, while restricting high-protein foods like steak, chicken, eggs, and dairy.

Nursing Management (PKU)

• Teach the family about dietary restrictions

• Foods low in phenylalanine levels:

○ Some vegetables (except

legumes), Fruits, Juices,

Cereals, Bread, Starches

● Encourage prenatal testing (genetic counseling) for future pregnancies

Maple Syrup Urine Disease (MSUD)

• Body can’t breakdown branched amino acids

○ Buildup of Amino Acids and Toxic Metabolic Byproducts

■ Valine, Leucine, Isoleucine

■ Deficiency of chromosome 19 - BCKHDA

● Amino acid disorder

● Problems in breaking down amino acids found in protein

● Absence of a group of enzymes called "branched-chain ketoacid dehydrogenase" (BCKAD)

Classic MSUD

First symptoms about 3 to 5 days

a. Poor appetite/feeding

b. Irritability/high pitch

c. Incessant crying

d. Characteristic odor of cerumen and urine

2. After a few days, they:

a. First symptoms about 3 to 5 days

b. Poor appetite/feeding

c. Irritability/high pitch

d. Incessant crying

e. Characteristic odor of cerumen and urine

Diagnostic Evaluation (MSUD)

1. Plasma amino acid test (increased Leucine, Isoleucine and Valine)

2. Urine organic acid test (increased alpha-keto acids

3. Genetic testing (mutation testing)

a. There will be signs of ketosis (buildup of ketones, a by-product of burning fat) and excess acid in the blood (acidosis).

Treatment Management (MSUD)

1. Medical Formula (isoleucine, leucine, valine free milk)

2. Diet low in branched-chain amino acids

3. Supplements

4. Tracking BCAA levels

5. Hemodialysis

6. Liver transplant

7. Low-protein diet