Analysis of a case of 42yr old female with multiple health events since birth

I've 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 come up with a diagnosis and treatment plan. 

You can find the entire real patient clinical problem in this link here... https://classworkdecjan.blogspot.com/2019/05/42-f-with-severe-regular-edema-with_17.html?m=1

Following is my analysis of this patient's problem:

The major problems encountered by the patient include:

1.Headache

2.Swelling over face and abdomen

3. Reduced sleep

4. Cognitive impairment

5. Reduced exercise tolerance

6. Reduced urination and sweating

 HEADACHE :

• Since the age of 2 yrs
• Gradually progressive 
• One sided mostly the left
• Frequency : 2times / week (in summers) 
• Lasts for long duration (sometimes upto 3 wks) 
• Aggravated on : emotional stress, hot climate, when sick
• Relieved on medication :Triptans
• Associated with : visual aura (in the form of mild cresent light to severe as blindness lasting for 2hrs) ,preceeding inflammation on the scalp, preceeding spinning movements, stuttering, left side hemiparesis. 

This description led me to diagnosis of Hemiplegic migraine. 

But further investigatios are required to confirm the diagnosis. 

Investigations required:

• CT/MRI of head 
• Familial Hemiplegic Migraine genetic testing

Treatment : continue with TRIPTANS

                      avoid stress and hot climates. 

                           

SWELLING:

• mostly on the face and abdomen sometimes involves even gut, hands and feet
• Since birth 
• Imtermittent
• progressess by the end of the day ( from noon to evening) 
• Aggravated on : food ( high carbs, fava beans) , emotional stress ,  smoking(swelling occurs after 1hr of smoking) , exercise and diuretics
• Relieved on : fasting, rest (1-3 wks) , Cimetidine
• Associated with : SOB, reduced urination

From the above details I probably think that the swelling is due to ANGIOEDEMA. 

My points of explanation for this are:

 Firstly there is underlying G6PD deficiency (which I will elaborate later) and her aggravating factors ( food, smoking, exercise) cause release of ROS , these ros cause stimulation of inflammatory substances like histamine in mast cells and also membrane instability leading to angioedema. 

Investigations required: 

   Skin test and blood test(C1 estarase inhibitor) 

Treatment : Cimetidine

                      avoid triggering factors. 

REDUCED SLEEP:

•  Since birth
• 2-4 hrs /day
• No REM sleep
• Sleep improved with L-Serine 20 mg (6-7 hrs /day with REM sleep of 3 1/2 hrs) [L-Serine improves sleep initiation and reduce night awakening]

This reduced sleep can be due to reduced NADPH and reduced Glycine. 

Treatment : continue with L-Serine

COGNITIVE IMPAIRMENT :

  Like BIPOLAR DISORDER , ADHD (Attention deficit hyperactivity disorder).

Probable reasons could be :

• Lack of sleep
• ANKK1 mutation
• Hyper homocysteine
• Behcets disease (? ) 

Treatment : 

        CBT (cognitive behavioral therapy) 

         Avoid stress factors by doing performing some       activities that distract you from worries. 

REDUCED EXERCISE TOLERANCE :

   Severe post exercise swelling , early fatigue. 

 Swelling could be due to release of ROS (as said above) and fatigue due to AMPD1deficiency(explained later) as stated from her genetics. 

Rx : D-Ribose (which helped her) 

REDUCED URINATION AND SWEATING : 

   Severely reduced urination, thirst and sweating when swelled up and improved when her swelling subsided. 

Also she takes a lots and lots of salt. 

Probable mechanism : 

         kidney needs lots of energy for ions active transport and hence water balance in body and her urge for salt as when she might be loosing them heavily, also a reason may be why she urinate less is because she loose lots of ions as not having enough nadph & atp for their absoption by active transport mechanism. 

Rx : L-Serine , cimetidine helped her

        Fasting helped her a lot ( but I do not suggest for     complete fasting ). 

As mentioned in her genetics , there is G6PD deficiency , AMPD1 deficiency and hyper homocysteine they fitted into the cause for most of her complaints. 

G6PD DEFICIENCY :

  It is an X-linked inborn errors of metabolism that predisposes to red blood cell breakdown. 

Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme in the pentose phosphate pathway (also known as the HMP shunt pathway). G6PD converts glucose-6-phosphate into 6-phosphoglucono-δ-lactone and is the rate-limiting enzyme of this metabolic pathway that supplies reducing energy to cells by maintaining the level of the reduced form of the co-enzyme nicotinamide adenine dinucleotide phosphate (NADPH). The NADPH in turn maintains the supply of reduced glutathione in the cells. Reduced glutathione is required to maintain and protect the RBC membrane from ROS. 

Thus deficiency of G6PD lead her to hemolysis, paleness, fatigue, jaundice, tachycardia, dark urine, SOB. 

Triggers : 

     viral/bacterial infections, drugs like antimalarial and sulfa drugs, fava beans, exercise, alcohol, smoking, stress, lack of sleep, high carbs diet. 

Investigations suggesting this  is her genetic testing for G6PD gene.

Rx : 

• Avoid triggering factors (drugs, foods,...) 
• Supportive treatment
• Vit B12 and Folic acid supplements
• NAC (helps in building antioxidants) 

AMPD1 DEFICIENCY : 

 Adenosine monophosphate deaminase deficiency, is an inherited disorder of muscular energy metabolismwith lack of AMP deaminase activity in skeletal muscle. 

Normally, AMPD catalyze the deamination of AMP that which leads to formationof fumarate via purine nucleotide cycle and this fumarate is an intermediate in Krebs cycle that finally required in ATP production.

So the deficiency of AMPD leads to reduced ATP production. 

As the patient genetic study and her exercise intolerance and fatigue on exertion are suggestive of AMPD1 deficiency. Moreover her response to D-Ribose was very satisfactory. 

Rx : 

      continue with D-Ribose(0.1-0.15 mg/kg/hr) . 

HYPER HOMOCYSTEINE : 

Homocysteine is an amino acid not supplied by the diet that can be converted into cysteine or recycled into methionine, an essential amino acid, with the aid of specific vitamins like B12, B6, Folic acid. 

Elevated levels of homocysteine can increase the risk of atherosclerosis by causing endothelial layer injury, promoting inflammation, and increasing oxidative stress. However, the exact mechanism is still unknown, and more research needs to be done to identify the pathophysiology. In relation to brain atrophy and cognitive decline, the correlation with elevated homocysteine levels is unclear but has been speculated to be a finding related to vitamin deficiencies. 

Factors in favour of her developing hyper homocysteine include signs and symptoms of Vit B12, B6 and folic acid deficiency like weakness, fatigue, mood changes, SOB etc also Other diseases that correlate with elevated homocysteine levels include hip fracture, cognitive decline, osteoporosis, chronic kidney disease, hypothyroidism, Alzheimer disease, and schizophrenia.

Rx: 

     low homocysteine diet

     Bit B12, B6, folic acid supplements. 

BEHCETS DISEASE : 

She was recently diagnosed wit behcets disease she said. 

BEHCETS DISEASE is an autoimmune disease associated with systemic vasculitis and immune complex deposition. 

Complaints suggestive of her having behcets disease include: 

• Mucosal ulceration
• Skin lesions
• Rashes on face 
• activation of warts and EBV(? ) 
• obscuration of vision and led to blind for which lasik failed. 

Rx : she is on Colchicine (but there is possible risk of   hemolysis in G6PD). So I prefer her to shift to cytotoxic   drugs. 

OTHERS :

Her other health events I could not explain throughly :

• VWF Disease type 1 : cause for easy bruising and dark stools, menorrhagia. 
• WNK1 mutation : PAH2 (high BP, anhydrosis, hyper kalemia) . 
• Raised ICT followed by CSF rhinorrhea for 10mins at the age of 35.
• Menorrhagia, with clots, ectopic pregnancy, excessive hair growth on face/neck/toes &legs, hairloss on scalp are explanatory for PCOS. 
• Fluctuating BP (high with fava) POTS, difference in both arms. 
• Hyperinflation of lungs and H/O  smoking suggestive of COPD but further evaluation needed. 

REFERENCES: 

1.https://classworkdecjan.blogspot.com/2019/05/42-f-with-severe-regular-edema-with_17.html?m=1

2.Wikipedia