42yr old female suffering with multiple ailments

I have been given this case to solve and interpret to enhace my competency and as an attempt to understand the topic of  "patient clinical data analysis"

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

Priority of her complains according to my analysis

1) Severe headache associated with visual aura.

• loss of function & numbness  on left side 
• Falling to left side
•  Vertigo
•  csf rhinorrhea from left nostril
•  Aggravated by :stress,mensus, birth control pills
•  Headache was relieved by taking medication (triptans)

Diagnosis :

• Most probably hemiplegic migraine

Differential diagnosis may be 

• Space occupying lesion on right side.                                     
•  Increased ICT 

• Secondary headache syndrome

• Cerebral vasculitis ( presents as headache & neurological deficit )

 

HEMIPLEGIC MIGRAINE 

     What Causes Them?

So far, researchers have found four genes linked with hemiplegic migraine:

• CACNA1A
• ATP1A2
• SCN1A
• PRRT2
• CACNA1A codes for CAV2.1 calcium channels in brain . Mutation in that gene impairs the ca+2 channels influx there by impairing the release of neurotransmitors(serotonin) & may cause migraine attack. 
• * CACNA1A gene mutation is associated with episodic ataxia  
• This may explains why  she gets migraine attack & ataxia 

Reference : 

https://ghr.nlm.nih.gov/gene/CACNA1A

FURTHER INVESTIGATIONS : 

• To rule out space occupying  lesions - neuro imaging mri 
• For ICT - lumbar puncture 
• Neurological examination 

 Left hand numbess May be due to  her T1 vertebral hemangioma compressing only left side

2) COGNITIVE IMPAIRMENT

There are plethora of reasons for cognitive deficits. 

• In this patient I think MTHFR GENE mutation is responsible. 

MTHFR gene mutation ----> increase in         homocysteinaemia  ----> increased risk of osteopososis , stroke , Alzeimers  disease.

•  Homocysteinaemia causes ectopis lentis. This may be the reason for her poor sight. 

This may also explain the multiple fractures , memory loss in this patient. 

• MTHFR MUTATION ---> impaired metabolism of vitB12 & folic acid --->psychomotor problems. 
• MTHFR MUTATION is associated with increased risk of  ADHD & AUTISM.Migriane with aura 

 

This patient is diagnosed with ADHD & AUTISM at 35 yrs. 

 

Reference https://www.psychologytoday.com/us/basics/adhd

INVESTIGATIONS : 

• serum vit b12 levels analysis 
• Peripheral smear 
• Increased homocysteine in urine

EDEMA 

• G6pd deficiency ----> hemolysis --->

 Increase bilirubin---> increased urobilin ---> toxic injury to kidney ---> 

 Acute kidney injury ---> repetitive kidney infections ,  Edema , oliguria

•  May  also be due to malnutrition and decreased protein intake  as she has less food intake 

DIFFUCULTY IN RESPIRATION  

May be due to her hiatal hernia

EXERCISE INDUCED FATIGUE  

          May be due to AMPD 1 MUTATION. 

AMPD 1 MUTATION ----> AMP deaminase disfunction -----> impairs the ability of muscles to produce energy 

SLEEPLESSNESS

 

The reason for sleep disturbances could be G6PD deficiency: G6PD deficiency results in impaired glycolysis. As a result Glycine (inhibitory neurotransmitter) is not produced.

   2. As she was diagnosed with ADHD(Attention Deficit Hyperkinetic Disorder), it could also be a reason for sleep disturbances.

 Treatment:

   - she is taking L Serine(orally)

    L Serine converts to Glycine invivo, which is an inhibitory neurotransmitter.

 Increased pain tolerance  

Differential diagnosis : 

• Dissociative disorders 
• Fibromyalgia ( her mother is known case of fibromyalgia )
• Hereditary sensory autonomic neuropathy type -2  as seen in WNK1 MUTATION 
• prader willi syndrome 

WNK1 MUTATION  :different WNK1 isoforms are important in several functions in the body, including blood pressure regulation and pain sensation 

• HSAN TPYE 2 associated with wnk1 mutation 

Reference https://ghr.nlm.nih.gov/condition/hereditary-sensory-and-autonomic-neuropathy-type-ii

PRADER WILLI SYNDROME (PWS) :

PWS  is caused by deletion of paternal chromosome 15

PWS CLINICAL FEATURES	REASON in pws	SYMPTOM IN PATIENT
Sleep distubances	MAGEL'S 2 GENE DELETION which is responsible for regulating circadian rhythmes	present.
Hypotonia	Megel's 2 gene deletion . https://www.google.com/amp/s/www.fpwr.org/fpwr-funded-projects/loss-of-magel2-and-hypotonia-in-prader-willi-syndrome%3fhs_amp=true	present
Scoliosis	Due to low muscle tone	present
Pcos	due to adrenarche . Adrenarche shows incresed DHEAS . https://en.m.wikipedia.org/wiki/Adrenarche	present pcos is may be responsible for her ectopic pregnancy.  she also has abnormal hair growrh ( hirsutism)
High pain Tolerance	NECDIN gene deletion which plays a role  in terminal differentiaon of neurons https://www.genecards.org/cgi-bin/carddisp.pl?gene=MAGEL2#summaries	present
Autism & ADHD	hypothalmus is affected leading to behavioral changes ( MEGEL 2 GENE  DISFUNCTION )	PRESENT
Insatietable hunger & obesity	present	Absent  patient has anorexia & specific reason for it should be ruled out. Due to anorexia  there is no obesity

DYSLEXIA  is diagnosed in this patient.  Dyslexia most of times associated with ADHD & autism . 

Genetics : associated with DYX1C1 present on chromosome 15 .

Reference https://en.m.wikipedia.org/wiki/Dyslexia

In pws  - chromosome 15 deletion. 

•  MAGEL 2 belong to MAGE family. (melanoma antigen gene ) 
• MEGEL2  DISFUNCTION present in PWS
• MAGE mutations are common in melanoma. 
• Reference https://pubmed.ncbi.nlm.nih.gov/20862285/
• Pt was diagnosed with melanoma . This may explain the coorelation . 

There are many similariteis in  clinical features of pws & this pt. But not sure  because most important clinical feature  hyperphagia & obesity are absent in this patient. 

Full genome study is required for confirmation of PWS

 FURTHER INVESTIGATIONS : 

• DOLORIMETRY - assess pain threshold 
• Pain intensity scales 
• Full genome study 

RECURRENT MOUTH ULCERS 

• Mouth ulcers are relapsing 
•  May be autoimmune in origin  
• Associated with arthritis - patient has hip & knee joint pain. 

Differential diagnosis : 

• Behcet's  disease
• Reactive arthritis 

Pt is diagnosed with behcet's disease recently.

 

BEHCET'S DISEASE :

•   Associated with HLA - B51 
• It is thought  to be an inflammatory reaction triggered by streptococcus in genitically predisposed individuals ( she reported she has recurrent streptococcal infections  for which she also  got vaccinated ) 

 pt.  May Presents with mouth ulcers , arthritis , vasculitis , increased ICT 

• Vasculitis ----> may occlude  the vessels supplying optic nerve ----> acute optic neuropathy 

This may explain the  transient vision loss in this patient. 

•  There may be increased  ICT secondary to cerebral vasculitis . 

 

Cerebral vasculitis ---> increased ICT -->

Headache & CSF rhinnorhea. 

 

This may explain that pt has a episode of headache associated CSF rhinorrhea  

Refetence :  

 https://en.m.wikipedia.org/wiki/Beh%C3%A7et%27s_disease

FURTHER INVESTIGATION

•  fundoscopy  for optic nerve 
• Csf analysis by lumbar puncture 
• Pathergy test