Exam V: Genetic Diseases

Question 1

Sickle Cell Anemia

Answer 1

Autosomal Recessive
Heterozygotes: advantage because little side effects of having one mutated allele, but have resistance to malaria caused by Plasmodium falciparum

A mutated gene results in RBCs that are deficient in O2 transport protein (Hb) causing them to develop a sickle/crescent shape
Sickle cells are stiff and sticky and therefore tend to block blood flow in the blood vessels of the limbs and organs (ISCHEMIA, PAIN, NECROSIS)
Healthy red blood cells typically function for 2-3 months, but sickled cells only last 10–20 days (ANEMIA)

Question 2

Sick Cell Anemia: Signs and Symptoms

Answer 2

Symptoms don’t appear in infants until they are 4 months old
First sign can be swelling on the back of the hands and feet (hand-foot syndrome)
Most common symptom is anemia (severe fatigue) and pain.
Sickle cell crisis (sudden pain throughout the body) can affect many parts of the body and cause many complications

Question 3

Hereditary Spherocytosis

Answer 3

Caused by intrinsic defects in the RBC membrane skeleton altering the shape to be spherical and prone to splenic sequestration/destruction via macrophages
An Autosomal Dominant Inheritance Pattern is seen in 75% cases.

Mutations in spectrin, ankyrin, band 4.2, or band 3 cause cells to adopt a spherical shape

Question 4

Hereditary Spherocytosis: Signs and Symptoms

Answer 4

Most Specific: Spherocytosis
Reticulocytosis
Marrow Erythoid Hyperplasia
Mild Jaundice
Cholelithiasis 
Moderate splenomegaly 
Increased sensitivity to osmotic lysis aka lyse faster than normal RBCs
Increased mean cell Hb concentration due to dehydration

Question 5

Hereditary Spherocytosis: Treatment

Answer 5

Splenectomy- corrects for the anemia, but the membrane defect remains

Supportive Care
Folic Acid
Blood Transfusion/Erythropoietin
Hematopoietic cell transplantation

Question 6

Ornithine Transcarbamylase Deficiency(OTC Deficiency)

Answer 6

X Linked Recessive

Breakdown of amino acids generates NH4+, which needs to be eliminated from the body

Without OTC:
Carbamyl Phosphate can’t enter the urea cycle
Ammonia builds up in the blood (hyperammonemia)

Question 7

OTC Deficiency: Signs and Symptoms

Answer 7

Elevated ammonia levels causes cerebral edema and consequential brain damage
Seizures, developmental delays, ADHD, intellectual deficiencies
Increased extracellular potassium levels causes increased frequency of seizures
Liver failure from increased levels of liver enzymes and coagulopathy
Symptoms depend on early or late onset

Question 8

OTC Deficiency: Dx

Answer 8

Severe neonatal-onset disease:
Plasma amino acid analysis (PAA)
High glutamine & low citrulline indicates OTC deficiency

Males & females of all ages:
Urine organic acid analysis (UOA)
Elevated acid concentration indicates OTC deficiency

Confirming the diagnosis
Mutation in OTC gene
Decreased OTC enzyme activity in liver
Pedigree analysis

Question 9

G6PD Deficiency

Answer 9

X Linked Recessive
Triggered by bacteria, viral infection, certain drugs (malaria medication) or eating fava beans
Newborns are screened for this deficiency in the hospital routinely ONLY in 2 states (PA & DC)

Accumulation of reactive 02 species= damage RBC’s
Leads to formation of Heinz bodies

Question 10

G6PD Deficiency: Signs and Symptoms

Answer 10

Symptoms:
Hemolytic Anemia
Low red blood cell count, low Hb, paleness, jaundice, Dark colored urine, fatigue, shortness of breath, rapid HR, RBC with Heinz bodies
If left untreated can lead to kidney failure & death
Most people have no signs or symptoms
Patients recover quickly in about 8 days ( when new RBCs are created they have normal G6PD activity)

Question 11

Hemochromatosis: Types

Answer 11

Excessive iron absorption deposited in parenchymal organs such as liver, pancreas, heart, joints, endocrine organs

Primary: Hereditary hemochromatosis
Excess Iron accumulation due to gene mutation

Secondary: Parenteral administration of iron
Blood transfusions causing hemolysis due to underlying condition (i.e. Beta Thalassemia)
excessive iron release from lysed RBC’s

Question 12

Hemochromatosis: Pathogenesis

Answer 12

Autosomal Recessive
Higher penetrance in Caucasians and Males (Celtic Disease)
Abnormal regulation of intestinal absorption
Iron accumulation toxic to liver
Reversible → not fatally injured

Hepcidin (HAMP gene) secreted by liver 
Main regulator for decreasing iron absorption
Lowers plasma iron levels 
Deficiency → iron overload
Mutation in the HFE gene

Question 13

Hemochromatosis: Signs and Symptoms

Answer 13

Two most common: Chronic fatigue and joint pain

Other symptoms:
Lack of energy
Diabetes Mellitus (glucose intolerance)
Abdominal pain
Memory fog 
Loss of sex drive
Heart flutters 
Irregular heart beat 
Pain in the knuckles of the pointer and middle finger, collectively called “The Iron Fist,” is the only sign or symptom specific to hemochromatosis.

Question 14

Hemochromatosis: Fully Developed

Answer 14

Micronodular cirrhosis → all patients
Golden yellow hemosiderin granules of hepatocyte cytoplasm
Can use Prussian Blue Stain for Iron
Diabetes Mellitus → 75%-80%
Bronze Diabetes: preferential iron deposition on pancreatic beta cells leading to death
Abnormal skin pigmentation → 75%-80%
Joints: Synovitis

Question 15

Hemochromatosis: Treatment

Answer 15

Blood donation/Therapeutic Phlebotomy:
Regular blood donation → every 8 weeks
A person with severe iron overload → as much as 8 times in a single month

Iron Chelation Therapy: increase excretion of iron

Dietary Changes:
Avoid Iron supplements
Limit Vitamin C and Alcohol intake
Avoid Uncooked Shellfish

Question 16

Wilson’s Disease

Answer 16

Autosomal Recessive or spontaneous mutation
Women affected to 2:1 ratio compared to men
Genetic defect: ATP7B, which encodes metal transporting ATPase causing reduced excretion of copper
Systemic accumulation of copper in liver, brain, kidneys, cornea, heart, pancreas and joints

Question 17

Wilson’s Disease: Signs and Symptoms

Answer 17

Manifests at ages 6 - 40
Movement disorders, tremors, involuntary movements, drooling, dystonia, seizures, migraines
Insomnia depression, personality change, psychosis, jaundice, bruising
Scarring of liver, liver failure, persistent neurological problems, kidney problems, psychological problems
Kayser-Fleischer Rings- copper build up in eyes

Question 18

Wilson’s Disease Testing

Answer 18

Genetic testing: look for Autosomal recessive inheritance
Blood test and urine test to measure high copper levels

Diffucult to diagnose- symptoms match other liver diseases such as hepatitis

Eye exam- look for copper deposits/sunflower cataracts

Liver Biopsy

Question 19

Wilson’s Disease: Treatment

Answer 19

Chelation therapy drugs to bind copper and increase its urinary excretion = Penicillamine, Trientine, Zinc Acetate

Successful treatment requires lifelong adherence to drug regimen and avoidance of foods high in copper
Liver, shellfish, mushrooms, nuts, chocolate
Severe liver damage would require a liver transplant

Question 20

Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCAD Deficiency)

Answer 20

Autosomal recessive disorder
Gene involved: ACADM where Lys is replaced by glutamic acid

MCADDis a disorder of fatty acid oxidationthat impairs the body’s ability to break down medium-chain fatty acidintoacetyl-CoA

When the MCAD enzyme deficient, the body cannot use fat for energy, and must rely solely on glucose. Since limited glucose available, the body tries to use fat
This leads to hypoglycemia, and to the build up of harmful substances in the blood causing damage to brain, liver, and other organs

Question 21

MCAD Deficiency: Signs and Symptoms

Answer 21

Hypoglycemia
Excessive vomiting
Lethargy
Common flu-like symptoms
Seizures
Coma
Sudden Infant Death Syndrome (SIDS) is also possible

Question 22

MCAD Deficiency: Pathology

Answer 22

Accumulation of lipids in organs dependent upon fatty acid oxidation such as liver, heart, kidney, and skeletal muscle fibers, which can lead to liver failure
Accumulation of lipids may disappear without any damage once homeostasis is restored

Increased levels of intermediate metabolites of medium chain fatty acids associated with MCADD

Octanoylcarnitine (C8) is the primary MCADD marker

Question 23

MCAD Deficiency: Tx

Answer 23

Simple carbohydrates by mouth
IV glucose to reverse catabolism and sustain anabolism
Avoid fasting
Low fat diet
L-carnitine supplements
Always monitor and inform physician during cases of poor appetite, low energy or excessive sleepiness, vomiting, diarrhea, infection, & fever

Question 24

Galactosemia

Answer 24

Autosomal recessive disorder characterized by the deficiency of enzymes involved in the galactose metabolic pathway

Type I: Galactose-1-phosphate uridylyltransferase deficiency (classic galactosemia, the most common and most severe form); GALT mutation

Type II: Galactokinase deficiency; GALK1 mutation

Type III: Galactose-6-phosphate epimerase deficiency; GALE mutation

Question 25

Galactosemia: Signs and Symptoms

Answer 25

``` Cataracts Liver cirrhosis Jaundice Mental retardation Kidney damage Lethargy Failure to thrive Death (if galactose present in diet) ```

Question 26

Galactosemia: Newborn Screening

Answer 26

Urine or blood test (heel stick) that checks for enzymes needed to change galactose into glucose. If these enzymes are lacking there will be high levels of galactose in the blood and urine. Blood Test Levels for GALT Prenatal: Amniocentesis or Chronic Villus Sampling

Question 27

Galactosemia: Tx

Answer 27

Avoiding all products containing lactose or galactose Alternative diets for babies: meat based formula or soy based formula along with calcium supplement Avoid this: Dairy products, puddings, cookies, food coloring, instant potatoes, some canned or frozen foods (if lactose is listed as an ingredient)

Question 28

Hemophilia A

Answer 28

X Linked Recessive Low Factor VII levels = easily bruised/bleed internally Signs/Symptoms: cola urine, tarry stools, coffee ground emesis Dx: Medical health history, evaluate clotting factor assays CBC, PTT, PT, fibrinogen tests Tx: Prophylactic treatment or Amicar

Question 29

Duchenne Muscular Dystrophy

Answer 29

X-Linked disease that is associated with deletions or frame shift mutations of dystrophin gene Do not present symptoms in infancy Dystrophin: Provides myofibril stability by binding actin filaments and β-dystroglycan Defects lead to membrane tears causing calcium influx causing muscle degeneration that is greater than repair which leads to replacement by collagen and fat cells

Question 30

Duchenne Muscular Dystrophy: Signs and Symptoms

Answer 30

Not seen at birth Walking is delayed and unstable Pseudo-hypertrophy of the lower leg Patients are wheelchair bound by the age of 10 They have a life expectancy of 25-30 years Eventually succumbing to respiratory insufficiency or heart failure Cardiomyopathy and arrhythmias develop in older patients Breathing problems Cognitive impairment is also seen in patients Joint contractures and scoliosis Gower’s Sign- getting up to standing position relying on arms

Question 31

Duchenne Muscular Dystrophy: Dx

Answer 31

Genetic testing showing a mutation of dystrophin on the X chromosome Blood tests showing an increased serum creatine kinase Muscle Biopsy showing muscle degeneration and the presence collagen and fat cells

Question 32

Duchenne Muscular Dystrophy: Tx

Answer 32

Braces: orthoses that support the foot and ankle or may even extend to the knee May be required to be worn at night Standing frames & wheelchairs Mechanical lifts, shower chairs, & electronic beds Medications Corticosteroids to aid in muscle development early on ACE inhibitors or Beta blockers can be used in cases with heart damage Therapy Range of motion & stretching exercise Low impact aerobics Breathing aids as respiratory muscles weaken

Question 33

Tyrosinemia I

Answer 33

Build-up of Fumarylacetoacetate Defective Enzyme: Fumarylacetoacetate Hydrolase Transmission: Autosomal Recessive Tyrosinemia Type 1 deficiency. Characteristic “Cabbage-Like Smell”, jaundice, excessive bleeding Increased levels of fumarylacetoacetate are toxic to the kidney and liver, and lead to increased risk of hepatocarcinoma development

Question 34

Tyrosinemia II

Answer 34

Defective Enzyme: Tyrosine Aminotransferase (TAT) Product Accumulated: Tyrosine Transmission: autosomal recessive Early SX: Photophobia Skin lesions/yellow tinted calluses on hands and feet Behavior/coordination changes, neurological defects, ataxia *Symptoms occur most often after eating

Question 35

Tyrosinemia III

Answer 35

Defective Enzyme: 4-hydroxyphenylpyruvic acid Dioxygenase (HPD) Product Accumulated: 4-hydroxylphenylpyruvate Transmission: Autosomal Recessive While there are many mutations, some result in the production of a truncated protein. This causes CNS issues including: 1) Mental Impairment 2) Seizures 3) Ataxia

Question 36

Alkaptonuria

Answer 36

AKA: Black Urine Disease Defective Enzyme: Homogentisate-1,2-Dioxygenase Product Accumulated: Homogentisate Transmission: Autosomal Dominant This causes CNS issues including: 1) Black/Ink-Looking Urine 2) After 30 years = weight-bearing joint pain 3) Pigmentation of the sclera and cartilage of the ear 4) Heart Failure

Question 37

Tyrosinemia/Alkatouria Testing

Answer 37

Neonates have screening tests for various genetic aberrations, including enzymatic deficiencies in the Tyrosine Catabolic Pathway If testing shows an anomaly, characterized as an “out-of-range” value, the physician will instruct the parents to have confirmatory testing performed such as urine and blood sampling

Question 38

Cystinuria

Answer 38

Autosomal recessive disorder Affecting genes SLC3A1 and SLC7A9 on chromosomes 2 and 19 respectively Causes malabsorption of basic or positively charged amino acids like Arginine, Cystine Genetic disease resulting in defective transport proteins that reabsorbs cystine into the renal tubular cells Results in clumping and precipitation of cystine into stones

Question 39

Cystinuria: Signs and Symptoms

Answer 39

Asymptomatic when no stones Nausea, vomiting, dull ache, pain that starts and stops abruptly, hematuria (reddish brown urine), hydronephrosis, and pyelonephritis Severe pain in the flank that radiates around the left side towards the pubic area Excruciating pain when passing the stone

Question 40

Cystinuria: Dx

Answer 40

Perform a routine CBC Blood sugar, urea, and creatinine test Look in urine for crystals *Cyanide nitroprusside test* Ultrasound and CT can be used, but are not reliable Genetic analysis to determine which mutation they have Give contrast by IVP, then use X-ray to determine Just X-ray gives a fuzzy gray appearance due to the sulfur content

Question 41

Cystinuria: Tx

Answer 41

Adequate hydration Alkalization of the urine Reduce salt and protein intake (especially methionine) Diet restrictions can prevent them ESWL (Extracorporeal Shock Wave Lithotripsy) If this does not work, then surgical removal (large stones)

Question 42

Phenylketonuria (PKU)

Answer 42

Autosomal Recessive Defective mutated genes for the enzyme phenylalanine hydroxylase (PAH) This enzyme is active in the liver, where it converts dietary phenylalanine into tyrosine If untreated, phenylalanine concentrations build up in the bloodstream and cause permanent damage to the brain

Question 43

Phenylketonuria (PKU): Signs and Symptoms

Answer 43

``` Eczema (skin rash) Mental retardation Hyperactivity Seizures Tremors Autism Delayed mental and social skills Unusual positioning of the hands Jerking movements of the arms or legs Mousy or musty odor of breath, skin, and urine Lighter skin, hair, eyes than brothers or sisters without the disease ```

Question 44

PKU: Dx

Answer 44

Guthrie Test in newborns High levels of Phe in the blood sample overcome the inhibition, and allow the bacteria to grow. If an elevated level of Phe is detected, the child is placed on a phenylalanine-restricted diet for the first several years

Question 45

PKU: Tx

Answer 45

Avoid high Phe foods: fish, dairy, diet soda, wheat, eggs, nuts/legumes, and meat Eat low Phe foods: vegetables, fruit, sugars, low protein foods, special breads/cookies/crackers ``` Extra BH4 (Kuvan) cofactor helps stabilize protein folding in some cases Phenylalanine ammonia lyase: bacterial enzyme for breaking down Phe Large neutral amino acids: competitors for Phe transporters in the brain ```

Question 46

Osteogenesis Imperfecta

Answer 46

Autosomal Dominant Most common mutations site are within the helical structure itself at the COL1A1 or COL1A2 genes Mutation may result in either a change in the structure of type 1 collagen or in the number of collagen molecules made Mutation location dictates severity of OI Other possible gene mutations: CRTAP and P3HI (autosomal recessive)

Question 47

Osteogenesis Imperfecta: Characteristics

Answer 47

``` Short stature Muscle weakness Scoliosis Bleeding (hematoma) Hearing loss Breathing problems Discoloration of sclera ```

Question 48

Osteogenesis Imperfecta: Dx

Answer 48

``` No definitive OI diagnostic exam Occurrence of fractures Common characteristics Differential DX of child abuse Quality/quantity of Type 1 collagen DNA sequencing COL1A1 and COL1A2 ```

Question 49

Osteogenesis Imperfecta: Mild Form Histology

Answer 49

Osteoporotic bone present Thick osteoid seams and reduced intercellular matrix Osteoclasts and osteocytes are normal Bone trabecullae are thin and disorganized Lamellar bone in diaphysis and metaphysis On electron microscopy → Osteoblasts show distended rough ER Collagen fibers are reduced in diameter

Question 50

Osteogenesis Imperfecta: Severe Form Histology

Answer 50

Severe form: Reveals hyperosteocytosis and increased vascular channels Reduced cortical bone thickness Lack of normal cortical bone formation Disorganization of the growth plate Give “popcorn calcification” appearance Woven bone is seen, with minimal osteoid bone and no lamellar bone

Question 51

Osteogenesis Imperfecta: Types

Answer 51

Types I-IV: dominant mutation in gene coding for type I collagen Types V-VI: unknown mutation; no type I collagen mutation Types VII-VIII: Recessive mutation in two genes that affect collagen ``` Most severe Type II (early death) Type III (usually wheelchair bound) ``` ``` Least severe Type I (Most common ```

Question 52

Junctional Epidermolysis Bullosa (JEB)

Answer 52

Also known as butterfly children, cotton wool babies, and crystal skin children Mutations in adhesion proteins Autosomal recessive Two different types: Herlitz JEB = more severe Non-Herlitz JEB = very mild Diagnosis: skin biopsy, genetic screening for implicated genes

Question 53

JEB: Signs and Symptoms

Answer 53

Blistering over large regions of the body Scarring and red, bumpy patches of granulation tissue Serious infections Loss of proteins, minerals, fluids Buildup of granulation tissue in airway Weak, hoarse cry and difficulty breathing Abnormalities of fingers and toes Malformed fingernails and toenails Alopecia Irregular tooth enamel Non-Herlitz JEB has milder symptoms, conditions improve after newborn period Herlitz JEB has very severe symptoms involving multiple organ systems

Question 54

JEB: Pathology

Answer 54

Non-functional adhesion proteins The epidermal layers easily detach from the dermis leaving it exposed to the external environment Accumulation of fluid/mucus causing blisters High risk of bacterial infections Lesions are non-healing or very slow to heal Affects all areas where epithelial tissues are present Airway GI tract

Question 55

JEB Tx

Answer 55

``` Manage the symptoms Drain and dress wounds appropriately Antibiotics for infection antibacterial for prevention Monitor fluid loss. Surgery C-section: reduces trauma to infant ``` Can be fatal in severe JEB

Question 56

Retinoblastoma

Answer 56

Rare type of eye cancer that develops in early childhood caused by mutated RB1 gene Hereditary (40%): occurs when a defective RB1 allele is inherited from one or both parents In the case of inheriting one defective RB1 allele, the other “good” allele must eventually undergo mutation for retinoblastoma to develop One or both eyes can be affected and increased risk for developing other secondary cancers Non-Hereditary (60%): arises from a mutation of both RB1 alleles within the cells of the eye Usually only one eye is affected No increased risk of developing secondary cancers in other areas of the body since the rest of the body has normal RB1 function No risk of passing on to children

Question 57

Retinoblastoma: Signs and Symptoms

Answer 57

Leukocoria, “cats eye”. A whitening/cloudiness of the eye is usually the first sign noticed by parents. Photographic “red eye” present in only one eye may be a sign Complaints of poor vision Strabismus: deviation of one or both eyes either inward or outward. Complaints of pain in the affected eye(s) due to increased intraocular pressure as the tumor grow

Question 58

Retinoblastoma: Dx

Answer 58

Diagnosis by physical examination (fundoscopic). Confirmation and further classification/staging by imaging. MRI is the preferred imaging modality, but ultrasound and CT may also be used

Question 59

Retinoblastoma: Pathology

Answer 59

Grossly appears as a white elevated mass with fine surface vessels. Microscopically appears as small, round-cell tumor. Flexner-Wintersteiner rosettes- characteristic finding in retinoblastoma Circular arrangement of cuboidal or short columnar tumor cells surrounding a central lumen. Nuclei displaced away from lumen

Question 60

Hereditary Non-Polyposis Colorectal Cancer (Lynch Syndrome)

Answer 60

Autosomal Dominant: effects mismatch repair genes and leads to accumulation of genetic damage Dx: MRI or IHC of tumor tissue, + gene test, or blood test Screening: colonoscopy, barium enema, stool hemocult tests

Question 61

MERRF

Answer 61

Myoclonic Epilepsy with Ragged Red Fibers Mitochondrial disorder that primarily affects the muscle and nervous system Caused by point mutation in the tRNA genes of mitochondrial DNA (mtDNA) Without functioning tRNA, proteins essential for oxidative phosphorylation cannot be synthesized and the mitochondria cannot create ATP Has largest effect on cells with the highest energy requirements

Question 62

MERRF Testing and Tx

Answer 62

Testing Lactic acidosis in blood and CSF (increased lactate and pyruvate) Elevated CSF protein concentration Muscle biopsy, genetic testing Treatment Coenzyme Q10 and L-Carnitine given in an attempt to improve mitochondrial function No actual cure for the disease Treatment for management of symptoms

Question 63

MERRF: Signs and Symptoms

Answer 63

Main Symptoms: Myoclonus (muscle twitches) Generalized epilepsy Ataxia (difficulty coordinating movements) Ragged-red fibers (in muscle biopsy) or mtDNA pathogenic variant identification Other symptos: myopathy (weakness) and spasticity (stiffness), exercise intolerance, short stature, hearing loss, optic atrophy and poor night vision, peripheral neuropathy (loss of sensation in extremities), dementia (deterioration of intellectual function), lactic acidosis

Question 64

β-Thalassemia

Answer 64

A relatively common genetic blood disorder involving reduced production of hemoglobin Major symptoms: anemia and predisposition to abnormal blood clotting Two Main Types: Thalassemia Major (aka Cooley’s Anemia) Thalassemia Intermedia Genetics: HBB Gene; Beta knot (no beta chains) and beta + (reduced beta chains) Autosomal Recessive Reduced production of adult hemoglobin (HbA) due to reduced or no synthesis of beta chains Leads to reduced red blood cell formation (erythropoiesis)

Question 65

β-Thalassemia Major

Answer 65

The more severe form of the disease ``` Signs & Symptoms Appear within first 2 years of life Development of life-threatening anemia Failure to thrive Jaundice Enlarged spleen, liver, and heart Misshapen bones Delayed puberty ```

Question 66

β-Thalassemia Intermedia

Answer 66

A milder form of the disease Signs & Symptoms: Can appear early in in childhood or later in life Mild to moderate anemia Possible slow growth and bone abnormalities Diagnosis generally between 6 and 12 years of age

Question 67

β-Thalassemia: Dx and Tx

Answer 67

Dx: Blood tests, CBC, DNA tests, blood smears, family history Hemoglobin Tests – check for types present Tx: Blood transfusion- required for survival in cases of Thalassemia Major, and improves quality of life in Thalassemia Intermedia Complications: buildup of iron in body over time leading to heart, liver, and hormone problems Chelation therapy to get rid of excess iron Folic Acid Supplements Bone Marrow transplant Future treatments: induce production of different types of hemoglobin

Question 68

β-Thalassemia: Histology

Answer 68

Red blood cell abnormalities in size and shape Target cells Basophilic stippling Fragmented red cells Nucleated immature red cells in periphery

Question 69

CPS I Deficiency

Answer 69

CPS 1 Deficiency is an autosomal recessive metabolic disorder mutation in the CPS 1 gene Disorder results in a shortage of Carbamoyl Phosphate Synthetase 1, a key enzyme in the urea cycle Inability for nitrogenous waste to be properly metabolized Leads to a buildup of ammonia within the body In healthy individuals

Question 70

CPS I Deficiency: Signs and Symptoms

Answer 70

Lethargy, hypotonia, vomiting, seizures Labs: high levels of ammonia, glutamine, and glutamate The blood work indicated an underperforming liver Genetic testing also ordered A liver biopsy would show pale, swollen hepatocytes

Question 71

CPS I Deficiency: Tx

Answer 71

Reduced protein intake A special ammonia reducing medication= Sodium Benzoate Recommends a special low protein formula