case of 42 year old female patients
Present Complaints of the patient :
1) Migraine with aura
2) Swelling which is mainly confined to face and abdomen
3) Sleep disturbances
4) Weakness on exertion
5) Increased tolerance to pain
Description of each complaint in detail :-
1) Migraine with Aura :
Onset - Sudden
Duration - Since 2 years of age so approximately 40 years
Progression - gradually progressive in intensity
Site - More in the left side
Associated complaints -
preceded by Aura,
generally associated with numbness of left hand and left face
feeling of rotation and spinning while sleeping on left side.
Past History : At age of 34 years, she had the worst headache as described by her due to which she lost her vision and began stuttering. It relieved by itself within 2 hours but her stuttering returned.
She also had mild memory loss as well as loss of function of left side ( dropping things intermittently and severe cramping of left arm.)
Also had a history of CSF rhinorrhoea from her left nostril.
At 41 years, she underwent genetic testing and was found to have G6PD deficiency, AMPD1 deficiency, MTHFR deficiency
Relieving Factors - Triptans
So from the above complaints the possible diagnosis could be :
HEMIPLEGIC MIGRAINE
Transient Ischemic Attack (But if she has TIA she is less likely to have other aura symptoms)
Infections like meningitis, encephalitis (she should have a fever, rash)
Brain tumours
Seizures with post-ictal paralysis
Metabolic Disturbances like Homocystinuria (as she has MTHFR deficiency, she can have high homocysteine levels)
MELAS ( Mitochondrial Encephalopathy Lactic Acidosis and Stroke like episodes)
In order to confirm the above diagnoses, the possible investigations needed would include:
CT and MRI of brain can confirm brain tumours, stroke, TIA
CSF analysis to diagnose infections
EEG to detect seizures
Magnetic Resonance Angiography to diagnose TIA
Intracranial pressure
Possible treatment modalities are :
Hemiplegic migraine - Triptans (which she is already consuming)
Surgery (Carotid endareterectomy) - TIA ( cannot give anticoagulants because she has G6PD Deficiency)
Anti epileptics - Seizures
2) Swelling:
Onset - since 1 year of age
Duration - approximately 40 years
Site - Face , Abdomen
Aggravating Factors -
Emotional Stress
Eating wrong food such as Fava beans
Exercise
Smoke
Relieving Factors - Rest
Associated factors - Shortness of breath, Decreased urination(increased on fasting), Dark coloured urine on exercise
Possible causes for swelling:
Since she has hemolytic anemia , she could have Right Heart Failure which is responsible for ascites and shortness of breath (because of Pulmonary artery hypertension).
And the hemolytic anemia could be responsible for her kidney infection because G6PD is responsible for production of NADPH. And since she has deficiency of G6PD, She does not have enough NADPH and ATP which resulted in loss of lots of ions thereby causing decrease in urination and Facial edema. ( refer to edited paragraph -1 )
It increased on emotional stress and eating fava beans because she has G6PD Deficiency.
Her shortness of breath could also be attributed to hiatal hernia.
Dark urine on exercise is suggestive of hemolysis which could be due to G6PD deficiency.
Differential diagnoses :
Could be Angioedema
Investigations done in this case are :
Hemogram - shows anemia
ECG - signs of Right Heart Failure
CXR - Left atrial enlargement in this case
SGPT, SGOT - elevated in this case suggestive of hemolysis
CUE - to show infection
Further investigations required are :
LDH -should be elevated To detect hemolysis
Total BIlirubin - should be elevated
Reticulocyte count - elevated
Urobilinogen
Heinz bodies in RBC on complete blood film
Beutler fluoroscent spot test - rapid test that identifies NADPH production by G6PD under UV Light
Haptoglobin ( decreased in hemolysis)
Direct Coomb's test - negative (suggestive of non autoimmune hemolytic anemia)
G6PD test
Skin tests for allergy (for angioedema)
Treatment :
Avoiding stress
Do not consume fava beans, sulpha drugs, antimalarials
Serine- increased urination
Excess salt consumption
3) Sleep disturbances:
Onset - since birth
Duration of sleep - 2-4 hours and no REM sleep
Possible causes :
AMPD1 Deficiency can cause sleep disturbances because Adenosine is an inhibitory neurotransmitter so it should help in sleep.
G6PD Deficiency impaired the glycolysis so glycine is not formed well . Glycine is also an inhibitory neurotransmitter.
Treatment taken by her :
L serine : works like glycine in brain so helps in better sleep
Cimetidine
4) Exercise Induced Fatigue :
Possible causes :
AMPD1 deficiency - lack of ATP hence the person gets easily tired.
Oxidative stress from excess of free radicals because of G6PD deficiency
Past history shows parents to be chain smokers which increases the oxidative stress.
Treatment given :
Ribose - helped her too because it provides ATP.
5) Increased tolerance to pain :
Onset - since 4 years of age ( cannot localize pain even now)
Associated complaints -
History of multiple falls
fracture of ankle
Never sweats
Differential Diagnosis:
CIPA (Congenital Intolerance to Pain With Anhydrosis)
Osteoarthritis could be responsible for multiple fractures. ( refer to edited paragraph -2 )
Investigations required :
Genetic testing for CIPA (NTRK 1 gene mutation can cause CIPA)
X Rays of limbs to diagnose osteoarthritis.
Treatment :
There is no treatment for CIPA so attention should be given to injuries to prevent infection and worsening injuries.
Other problems of the patient:
PCOS - Responsible for :
Dysmenorrhoea
Ectopic Pregnancy
Increased Hair loss
Bipolar disorders, Anxiety, Depression - could be because of less sleep and MTHFR mutation (Methylene Tetrahydrfolate Reductase Deficiency)
Rashes in face (could be SLE)
ADHD (Attention Deficit Hyperactivity Disease ) - Because of ANKK 1 mutation.
VWF mutation (Von Willebrand Factor ) - could be responsible for dysmenorrhoea.
The patient should go for whole genome sequencing to find out the other mutations.
EDITS :
1) G6PD deficiency might be responsible for her kidney infection because G6PD is the key regulatory enzyme in the HMP shunt with the production of NADPH that is required for protection against oxidative stress. Increased oxidative stress has been observed in many diseases including those related to renal damage. There is a higher prevalence of the G6PD deficiency in people with unexplained chronic kidney disease. In G6PD deficiency, massive intravascular hemolysis can cause acute renal failure, and acute tubular necrosis might complicate the severe hemolytic anemia.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5016010/
2) Osteoporosis could be responsible for her multiple fractures. In order to diagnose it, her serum Calcium levels must be checked. And since she has PCOS, she might be consuming OCPs which can decrease the Bone mineral density.
https://www.nature.com/articles/s41598-017-03685-x
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2822656/
RECENT UPDATES IN THE CASE AS OF MAY,2020 :
Presented with the Complaints of :
1) Oral ulcers
2) Vaginal ulcers
She got diagnosed with Behcets disease.
Possible causes for Behcets : She has multiple mutations making her susceptible to various autoimmune diseases like Behcets.
Symptoms which could be associated with Behcets in this patient are :
1) Headache- Because Behcets is characterised by inflammation within the brain (meningoencephalitis) which can cause a very severe headache associated with poor vision, ataxia, difficulty in speaking.
https://behcets.org.uk/information-for-patients/headache-in-behcets-disease/
2) Poor vision - Behcets is associated with Uveitis. That could be responsible for her poor vision.
3) Personality changes - Sometimes it might be the first symptom which should suggest Behçet’s disease.
Differentials for her complaints could be :
1) Herpes Simplex Labialis
2) Aphthous ulcers
3) SLE (also complains of rash on face)
Investigations required for the above diagnoses are:
1) Mainly based on clinical findings such as oral ulcers, genital ulcers.
2) Skin lesions such as acne, folliculitis, malar rash which are suggestive of SL
3) CSF Analysis which might show lymphocytosis In the case of Herpes Simplex Labialis.
4) CT and MRI may show periventricular white matter atrophy and lesions in the basal ganglia.
5) ESR ( elevated because of inflammation)
6) Complete ocular examination to see uveitis
7) Pathergy test
Treatment modalities : It does not have any treatment. The symptoms can be treated by
i) Topical therapy -
a) Creams for the oral and genital ulcers
b) Eye drops for uveitis
ii) Systemic therapy -
a) Immunosuppressants like Infliximab.
b) High dose corticosteroids.
c) Colchicine can be used for genital ulcers but cannot be used here because of her G6PD deficiency.
iii) Cognitive Behavioural Therapy - which she is undergoing.