CASE DISCUSSION

I have been given this case to solve in an attempt to understand the topic of "Patient Clinical Data Analysis" to develop my competency in reading and comprehending clinical data including history, clinical findings, investigations and diagnosis with a treatment plan.

You can find the entire real patient clinical problem in the following link:
http://classworkdecjan.blogspot.com/2019/05/42-f-with-severe-regular-edema-with_17.html#comment-form

Following is my analysis of the patient's problem. The problems in the order of priority I found are:

• Swelling(edema)
• Severe headache
• Muscle weakness
• Mouth ulcers
• Sensory processing disorder
• Excessive hair growth

Swelling

Swelling is present since 1 year age. It is mostly present on face and abdomen. Swelling aggravated on exposure to smoke, emotional stress,physical activity, certain drugs such as sulfa drugs, anti-malarials, and by taking foods such as fava beans. Swelling was associated with fatigue, breathing problems and tachycardia.

She also presented with severe jaundice at the time of birth.Urine is reduced(oliguria) and yellow in color.

She also had hemolytic episodes after a history of travelling.

Differential Diagnosis for swelling

• Cardiac failure
• Kidney problems
• Chronic severe anemia

Diagnosis

This above mentioned complaints are the features seen in increased oxidative stress. It is seen in a genetic disorder - G6PD deficiency.

1. She developed hemolytic episodes(swelling) after exposure to the triggering factors.
2. Jaundice at birth can be explained by hemolysis 
3. Excessive destruction of RBC can also damage kidney.This explains oliguria in the patient.
4. Due to decreased levels of hemoglobin, oxygen to the tissues also reduced leading to breathing difficulties
5. Due to oxidative stress ,there may be amyloid plaques in brain which explains loss of memory.

 G6PD Deficiency

Pathophysiology

Normally due to metabolic processes free radicals are released. To neutralize these free radicals, body produces anti-oxidants such as glutathione. This glutathione in reduced state donate electrons to the free radical and gets converted into oxidized glutathione.

The oxidized glutathione in the presence of glutathione reductase gets converted into reduced glutathione by converting NADPH to NADP. To replenish the NADPH, G6PD is used. G6PD reduces NADP to NADPH by oxidizing G6P(metabolite of glucose).

In case of G6PD deficiency which is X-linked recessive disorder,

Decreased levels of G6PD

↓

Decreased NADPH

↓

Decreased production of reduced glutathione

Due to the absence of glutathione, there is increase in free radicals leading to oxidative stress. Free radical causes hemolysis and hemoglobin molecules are damaged. Damaged hemoglobin precipitates in RBC leading to the formation of heinz bodies. Macrophages recognize the heinz bodies and engulf them, leading to the formation of bite cells. Often, only old RBCs are at risk of lysis. Therefore, hemolytic episodes are limited when young RBCs are formed.

Triggering factor in this case

• foods-fava beans 
• drugs-antimalarials
• infections- pt also had a history of pneumonia.Chronic infection triggers immune cells to to fight against the organism.This leads to release of free radicals which damage healthy cells and cause inflammation.In case of oxidative stress (which pt as due to G6PD deficiency),it triggers te inflammatory response more and releases more free radicals and cycle repeats which worsens the symptoms.
• smoke
• exertion

Investigations

Complete blood picture:

• decrease in hemoglobin
• increase in reticulocytes(to compensate the loss of RBC)
• increase in LDH
• increase in bilirubin 
• decrease in haptoglobulin

Peripheral smear:

• bite cells 
• heinz bodies

Enzyme detection - G6PD level should be detected

Genetic test-she underwent genetic testing at the age of 33yrs and was conformed by G6PD deficiency.

Treatment

• She has taken ribose for swelling 
• Avoid exposure to triggering factors 
• She is taking serine which helped her in treatment of oliguria.

     others

• Salt restriction 
• Blood transfusions 
• antioxidant vitamins

Severe Headache

She has severe headache since 2 years of age. Headache is sudden in onset and very severe. She develops aura before developing headache.

Aura - she develops rainbow colors, temporary blindness

           left hand numbness

           falling to left side (ataxia)

           stuttering of speech

           vertigo 

Severe headache was aggravated with menses, excess stress and use of birth-control pills.

At the age of 34 years she had one episode of headache on the left side and was associated with nasal discharge for ten minutes.

Diagnosis

In the above mentioned complaints, patient may be suffering from hemiplegic migraine.

Hemiplegic Migraine

Mutations in genes can lead to break down of body's ability to make certain proteins without which nerves cells have trouble in sending or receiving signals(serotonin).

Triggering factors in this case

• Intense physical activity 
• Skipping of meals 
• Travelling
• Exposure to smoke
• Stress
• Use of birth control pills
• Decreased sleep

Investigations

• CT and MRI 
• Tests of heart and blood vessels to rule out blood clots

Treatment 

She has taken triptans for migraine.

 Other medications that can be used are CGRP inhibitors.

Muscle Weakness

She develops muscle weakness fatigue on exertion. 

Differential Diagnosis

• AMPD-1 deficiency 
• Anemia

AMPD-1 Deficiency

It is inherited autosomal recessive disorder caused due to mutations in AMPD-1 gene. This gene makes enzyme AMP deaminase which plays a role in producing energy in skeletal muscles. Mutations in this gene disturbs the function of AMP deaminase leading to muscle problems.

Investigations

Genetic test: She was diagnosed for AMPD-1 deficiency heterzygous.

Treatment

She has been taking ribose - 2grams every hour in water.

Other medications which can be used are citrate monohydrate.

Mouth Ulcers

She develops mouth and vaginal ulcers when exposed to stress.These were more often until she took pnemonia vacccine at the age of 28 years.She also has blurring of vision ang head ache.She also has a history of  longterm knee and hip pain.She also had butterfly rash on the face.

Differential Diagnosis

• SLE
• Behcet's disease

Behcet's Disease

It is a rare disorder that causes blood vessel inflammation throughout the body.It is often associated with many mutation.It presents as mouth ulcers,eye problems,skin rashes and joint pains.

Investigations

• Mouth sores which has recurred 3 times in 12 months.
• Blood tests 
• Pathergy test
• Tests to rule out SLE.
• Genetic testing

Treatment

• Colchicine
• Corticosteroids
• Medications that supress immune system

Sensory processing disorder

• higher pain tolerance
• uncomfortable with physical contact 
• feels angry 
• used to throw tantrums

These features are suggestive of sensory process disorder.

Excessive hair growth

She has excessive hair growth on face, neck, toes and legs since childhood.

She has chronic abdominal pain at the time of menses.

Differential Diagnosis

• Congenital adrenal hyperplasia
• PCOS

Investigations

• Cortisol level -elevated
• CT scan - showed multiple ovarian cysts.

Treatment

• Spironolactone
• Eflornithine
• Anti androgens
• electrolysis

References - Various internet sources

                      Avinash Sir's case