Nephrotic syndrome

Three year old girl only child born to a  young couple was diagnosed as Nephrotic syndrome at one and half years of age. No consanguinity , no family history of kidney disorders . Antenatal natal ,postnatal developmental history all normal .

Was treated by an "adult nephrologist" with daily treatment .A different schedule was used (Not ISKDC ) Daily treatment 2 mg/kg once a day till remission and lower dose continuation .Total duration was two months . She came to remission in the first episode . She had relapses many times during this one and half years . She was on daily steroid through out . Increasing doses while on proteinuria ,but continuing daily treatment almost always the dose was almost one mg per kg .

She was put on cyclophosphamide orally 2.5 mg /kg for three months last year 

She was on Tab levamizol 2.5 mg per kg thrice a day for six months 

She is now on 20 mg daily steroid 

They noticed some difference in the way she looked at things and noticed some white shadow inside  her left eye . 

On examination, She is stunted. weight normal , Blood pressure above 95 centile both systolic and diastolic .

Obviously she is a case of Steroid dependent nephrotic syndrome. Poorly managed and followed up.

Critically analyzing,

1.Duration of steroid in the ISKDC regime or other where at least three  months of adequate dose steroid would have been better to reduce the number of relapses 

2.What about renal biopsy? Renal biopsy was not done .Is it justified to put her on Cyclophosphamide ?

 Yes , she responded to steroid , only thing she relapsed early and frequent relapses Every time she responds to steroid . Total cumulative dose of steroid caused toxicity . Renal biopsy is not indicated in cases of steroid dependent or frequent relapsing. 

We may choose one of the policies for treatment of these cases. 
Most favored one  is taper slowly ,titrate and continue low dose steroid .If the needed dose is 0.5 or .0.7 mg per kg ,continue for one and half years. Of course monitor for toxicity . 
If the minimum dose needed to prevent relapse is above this dose ,toxicity is high. ( or toxicity already occurred go for higher options . Here cyclophosphamide is the best . Either oral for three months as in the above case or monthly pulse for six months. 

3.Here proper monitoring of toxicity was lacking .There is stunting , Hypertension and cataract well established. 

Evaluation from Our institution 

 Her blood sugar, Electrolytes, calcium magnesium are normal 
Her system functions are normal , Hemoglobin is 11 grams 


Our Plans .

She is posted for cataract surgery next week 

After surgery What about her management after cataract surgery? 

Can we continue steroid ? 
if not What other drugs ? 

My first impression was 
" we cant continue steroids as she had all the major three complications. Now any way we have to continue the steroid till her surgery is over as her HPA axis is likely to be suppressed and surgery to be done under stress dose"
 After that ? 
She had already had a three month course of cyclophosphamide. So among the other choices Mycophenolate mofetil is the best. Tacrolymus and cyclosporin. Out of this we have few patients on MMF very good choice as they tolerate it very well , only thing is the cost .
Should we go for it ? "

We discussed with our ophthalmology team 

" Sir , we are going to take away the lens and she needs glass with full correction. Good progressive lenses  which can be worn for distant and reading she needs. Right side is normal now. Even if she develops cataract on the right , no problem we ll tackle it the same way. So if you need steroid , no problem , continue steroid "

That is better  logic . 

Now our task is to bring down the BP ,to make her fit for Aneasthesia . She is put on antihypertensive , Not on Nifedepine only 

Here  one question remian 

OK steroid low dose with good monitoring , dose just enough to prevent relapse is good option for long term.Here BP may come down with lower dose of steroid. and anti hypertensive also we may be able to taper and stop. 
What about stunting ? How much of this grade II stunting due to steroid. How much is it due to other reasons . . Will this steroid affect her final height
Both parents average height, we have plotted in graph, mid parental height . 
We ll follow up her closely , plot her height and weight for next six months 
That is the plan 


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Another ocular problem on steroid therapy which is likely to be missed is steroid induced glaucoma 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4544383/

Patient on long term steroid therapy we monitor most of the complications on daily basis or on follow ups. Eg Hypertension, Secondary diabetes ,infections like tuberculosis and fungal ,steroid induced myopathy ,avascular necrosis of hip osteoporosis etc .
In this context if patient complains of Persisting   head ache we ll search for common causes like Hypertension ,sinusitis .We may exclude benign intracranial hypertension ,TBM ,but very often wont think possibility of glaucoma . We ll check the fundus . 

But testing for Vision and ocular pressure rarely measured 

dengue

Each day we learn some thing new from ICU . Even when features are typical for an entity there ll be something unique in each case . 
Few experiences about cases referred to us as dengue from Periphery 
Common clinical features shared by all of them were fever more than one week , rash circulatory insufficiency and bit of ascitis and pleural effusion .
No doubt most of them turned out to be dengue ,few of them referred withNS1 positive or second week Dengue IgM positive. 
Managed as usual . 
Mortality in dengue is very unusual now with early detection and proper management according to guidelines. Cases missed if at all are due to major complications . 
Out of this case one turned out to be NSI and IgM degue negative , weil felix positive . He responded to Doxicycline. 

Here is another one Now under Treatment in PICU 
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Five year old boy developed fever 10 days back . No running nose cough bowel ,urinary disturbances. Fever subsided with paracetamol . Fever recurred after a gap of two days . High grade fever associated with abdominal pain and vomiting. Vomiting non -bile stained. No bowel disturbances. He was hospitalized and was put on Inj Cefotaxime and IV fluids . As the complaints worsened he was referred to us .
There was no history of rashes. bleeds joint pains . Urine and stools normally colored . 
Routine Investigations done from that hospital showed leucopenia thrombocytopenia . NS1 was done negative ( on the fourth day of fever )

No past history of significant illness. Immunized update. No visits outside . There is contact with a prolonged fever case in neighborhood.

On admission he was fully conscious ,dyspneic RR 80 per minute , no cyanosis. BP 70/40 Capillary refill time <3 second .No edema. No jaundice , No rash or bleeds, No  significant lymph node enlargement .
No pallor , no congestion eyes. irritable child .


System Examination

Upper GI , tongue, lips , throat normal 

Abdomen distended. Liver soft 4 cm non tender ,Spleen 3 cms soft 
Free fluid present 

Respiratory system . Trachea not shifted. Both side percussion dull infrascapular and axillary area . Scattered creps bilaterally . 

CVS. JVP not raised. Heart sounds normal intensity , no third heart sound 
CNS. no focal neurological deficit No signs of meningeal irriation
Provisional diagnosis of Dengue fever with warning signs was made and management accordingly done

Dengue igM negative 

Case was managed as dengue with meticulous fluid management and other supportive measures. 

He is recovering now

Message 

Dont rely too much on the Lab tests when clinical features are typical . NS1 and Ig M sensitivity is not hundred percent even when both taken together .

ENCEPHALITIS

11 year old girl who was healthy  till one week back had low grade fever followed by focal seizures on right  side. Seizure lasted five minutes.She regained consciousness but recurred after few hours. Fever subsided with one dose of paracetamol and lasted one day only .
No past history of significant illness, 
No contact wit PT, no ear discharge, head trauma
Born our of non consanguinous marriage,Antenatal ,natal postnatal period uneventful 
Development all normal , 
Immunised update
No family history of any neurological disorders 

On admission altered sensorium  ,
breathing normal ,
 BP 110/70 ,pulse 80/min,afebrile. 
No bleeds ,rash jaundice .
Eye movements normal ,pupils normal size and reaction fundus normal . 
other Cranial nerves normal 
Motor system ,power normal ,tone lower all limbs reflexes sluggish ,plantar up going 
No signs of meningeal irritation

Provisional diagnosis of ADEM /Herpes encephalitis was made 

First level investigations done 

LP done , CSF clear ,normal pressure 

With this Possibility of Encephaltis was high in the list and considering treatable encephalitis patient was put on Acyclovir and supportive measures 

Teaching points 

Patient had mild fever at onset only and dominant fever of encephalitis possibility of bacterial /tuberculosu meningitis not considered high in the list. 
With the blood and CSF result also was not favoring. we did nt put the patient on antibiotics. 
( This is a major decision , in an ICU setting with altered sensorium focal seizures and CSF showing cells it is dictum to put patient on treatable drugs , life is more important and time too short. So usually we take a policy to start management of pyogenic meningitis , acyclovir . At the same time send for virological studies , cultures. A policy to start this and stop later once the possibility is disproved. That ll be a better decision in an ICU . Here many points arguing against pyogenic or tuberculous and we took a decision not to start imperical antibiotics or ATT , but acyclovir only .

With evidence of diffuse brain involvement ,no fever possibility  of biochemical /metabolic , toxic /system function derangement to be ruled out .
Here  biochemical report did not support any of them . ie blood sugar ,electrolytes ,RFT ,LFT .Possibility of poisoning ,no circumstancial or clinical supporting evidences .
With the CSF finding of Lymphocytes possibility again increased for possibility of infection . But this may be misleading , the cell number is low , only lymphocytes. This can happen following any seizure. 
Argument for Herpes encephalitis usually are , cells , lymphocytes but more important is RBC in atraumatic LP . Here RBC were not there. Protein minimal elevation and sugar normal 

We sent the CSF for Virological studies . 

Next day patient developed this movements 

(consent taken from parents in writing )

These were abnormal movements ,(not seizures ) repetitive involving left hands picking hair and dress. Abnormal movement around mouth was prominent. 
Encephalitis with extrapyramidal movements were suggestive of Jap B encephaltis . But this movement is more suggestive of another entity - NMDA receptar encephaltis . In fact many cases earlier were diagnosed as Jap  B encephalitis  before this entity was not known . 
With this possibility in mind we send the CSF for NMDA receptar antibody and 
She was Put on Methylprednisolone and IVIG ( better to give both in this condition ) 

MRI was taken next day

This was the report from radiologist  , but i think there is some basal ganglion hyper intensity in flair images 

NMDA receptar antibody result came as high titre positive 
CSF virological study results from ICMR lab Manipal reported herpes , Jap B Dengue , westnile  viruses negative .

Sensorium improved , but she had seizure on the third day . She was put on Levetirazetam 
Since the last two days the abnormal movement worsened and sensorium deteriorating. Possibility of levetirazetam worsening the situation it was stopped and she was put on dilantin sodium . Short period she was on midazolam drip 

Movements are less today , but the sensorium same. 

Today She is put on Rituximab. 375 mg per meter square . 500 mg per day IV. 
For the abnormal movement she is put on Tetrabenazine 25 mg half tab BD.
Supportive measures continuing. Nutrition fluid ,electrolyte balance maintained mainly be IG tube feeding .


In this context just sharing experience with few cases of NMDA encephalitis came to us during  last two years. 
First case of NMDA was not diagnosed as we did nt give importance to the movement of his face , he was managed as jap B encephalitis . Only after two weeks this possibility was known , We send for NMDA receptar antibody , we managed with IVIG , no response. Later he responded to IVIG plus methylprednislone. Later he was investigated for underlying conditions like gonadal tumors , All negative. He was put on Azathioprim , Now asymptomatic
Another boy diagnosed early because of this experience. but did nt respond to IVIG plus methylprednisolone, We could mobilise Rituximab in govt set up Weely once was given four doses. 
He recovered , He also is under followup now on Azathioprim 

Shall update 

Please read 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2607118/

girl with rash

Six year old girl,previously healthy had low grade fever yesterday. As the fever subsided with paracetamol she was send to school today morning. Teacher noticed to have some odd skin lesions ,brought home. Local pediatrician was consulted ,he referred here 
At the time of admission , her vitals were stable, afebrile .These were the lesions noticed by the parents

No history of mucosal bleeds . She complains of body ache .No lymph nodes ,Joints normal 
Abdomen examination no organomegaly .
CVS and RS normal
CNS fully conscious, oriented, No focal neurological deficit 
No signs of meningeal irritation

Blood results done from outside showed , Total count of 17200 with 70 percent polymorphs . Platelet count 2.3 laksh .ESR was not done 

Possibilities considered 
Previously normal child cutaneous bluish lesions and conjuctival bleed following one day fever first possibility of some infections considered. 
Another possibility was ITP , but the platelet counts done from outside was not supporting. May be they can go wrong. Clinical features very well supporting ITP . 
As there were no pallor ,lymph node or organomegaly , possibility of malignancy was least 
Vasculitis as manifestation of connective tissue disorders at this age bit unusual . CVS examination and other features were not supporting infective endocarditis 
Out of the infections , Dengue was considered top in the list .
Conjuctival congestion , body ache was supporting.Circulatory status was normal . Main point here also was the investigation. Blood count done from outside were against .
Leptospirosis  was possible , but no jaundice , liver was just palpable soft . 
Another possibility considered was Ricketsiel infections which are increasingly reported . 

How to proceed 
Blood culture ,NS 1 antigen , PCV , LFT , Weil felix , Peripheral smear were send . Lepto not send  

Possibility of dengue was high in the list but few odd points clinically and investigations.No rash other than bleed, no cutaneous fleshing , This high count and neutrophil predomiance a bacterial infection was thought of. 
Ceftriaxone will cover possibility of menigococcemia and lepto also we decided to put here on Inj Ceftriaxone. 
Another thought was to put on Doxycycline.  

After four hours she had a generalised seizure. Neck stiffness positive. LP done showed neutrophils .gram stains showed meningococci.

Now question of chemoprophylaxis of contacts, contact tracing . 
We are getting meningococcal meningitis more often . 
Till late nintees we used to see many cases of meningococcemia then. Pyogenic meningitis as such was coming down.
Last year we had few cases of meningococal meningitis . Is it increasing ?


UPDATES 

24/03/2017
She responded very well to Inj .Ceftriaxone. Was afebrile from 48 hours of antibiotics. Antibiotics was continued for ten days 
On 9th day there was an interesting development
She developed painful swelling of right knee and right ankle joint on the same day . There was no fever, no rash , vitals were stable. System examination normal
All other joints were normal. Knee painful restriction of movement and patella tap positive 
USG knee and ankle was done , showed effusion

There was suggestion to aspirate , to put on NSAIDS , steroids. 

Antibiotics was stopped on next day , ie tenth day . No new drugs added, patient was kept on follow up. 
Logic ?
No evidence of active infection by organism . No fever no toxicity . Two joints simultaneously involved due to bacteria in a scenario where every other features support control of infection. Most likely this is immune mediated, reactive arthritis.
Ok , 
Now comes next question.
Should nt we give drugs for that. Steroids. NSAIDS. 
No need 
Swelling gradually reduced and patient discharged 

Case of empaema , simple problems during management

Four year old girl child presented with fever cough and dyspnea. No running nose ,cough was dry . 
She was hospitalized and was on Inj Ceftriaxone. 
As the dyspnea worsened she was referred to us.

First child born at term out of uneventful antenatal history was not asphyxiated. She had neonatal convulsions and was hospitalised for twenty days ? meningitis. 
Development was normal .
Last year she developed thrombocytopenia ,diagnosed and managed as ITP . 
There is history of abscess drained three times from different sites. Immunized update. 
No family history of any significant illness. ( No consanguinity) . No contact with tuberculosis. 

No past history of recurrent respiratory infection,ear discharge,purulent nasal discharge ,loose stools .

On admission she was dyspneic, fully-conscious, maintaining saturation above 90 percent with 50 percent oxygen circulatory status stable .
No focus of pyoderma or abscess. 
No rash or bleeds,
No Lymph nodes 
 No stigmata which grossly suggest inherited immunodeficiency . 

Her weight , height and Mid arm circumference was adequate for her age .

Respiratory system exam 

Upper airway normal 

Chest movement diminished on the right side.
 Apex and trachea shifted to left. Percussion stony dull in the right lower inter scapular axillary infra mammary areas. Air entry diminished same areas VR decreased ,no bronchial breathing, no added sounds. 

CVS normal except shift of apex to left 

P/A no organomegaly, no free fluid 

CNS fully conscious, no neurological deficit no Signs of meningeal irritation 

In short 

Four year old child admitted with fever ,dry cough and progressively worsening dyspnea. 
 Normal upper airway and mediastinal shift brings pathology below tracheal bifurcation. Mediastinal shift to left and stony dullness argue collection inside right pleural cavity. In view of fever in this age group most common reason is bacterial pneumonia with syn-pneumonic effusion. But here the cough is dry only and more  features of fluid in pleural cavity than parenchymal involvement. Possibility of empaema considered high . 

Is there an immunodeficienty behind ? 

Teaching points for PGs at this stage of history .

Multiple abscesses drained ,and now  empaema possibility of susceptibility to staph infection high ? Yes we should investigate in that line. Immunodeficiency states with abscess formation are 

1. Problems with phagocytosis of neutrophils 

2. Problems with respiratory burst ,chronic granulomatous disease. Usually boys but girls may be affected 

3. Jobs syndrome ,

other entities also 

Neutrophil related problem and bacterial infection . It may be adhesion problems , chemotaxis , phagocytosis or respiratory burst . 

In problems with adhesion , and chemotaxis, neutrophils wont reach the site of organism . So NO evidence of inflamation, no pus . Common reason for this state is any significant neurtopenia. ( No neutrophils to reach the site ) . In adhesion problems usually the neutrophil count in the peripheral blood ll be high ( They wont go out ,but remain inside )

Course 

USG confirmed empaema right side and ICD done .She was put on inj CP , Cloxacillin 200 mg/kg /day and Gentamicin .

Temperature touched baseline in two days .She was active ,playful .Exam showed trachea and apex in normal space ,dullness in the right infrascapular area , decreased VR and breathsounds same area.
So some more of pus remaining ? 

Repeat Xray chest and USG was done 

On the right side costophrenic angle was clear ,patchy pneumonia middle lobe. No abscess .
On the left side there was a circular translucency . 

Two questions remained

1.What is the reason for the Clinical findings in the right infrascapular area. Xray and repeat USG did nt show fluid .So this was attributed to pleural thickening (not a good explanation as this usually it takes two weeks )

2.What is the translucent shadow on the left side.?

Possibilities for this shadow 

1. cavity inside parenchyma .
2. Pleural adhesions 
3.abdominal viscera 
4.Pericardial cyst 

Out of this possibility of abdominal viscera was less likely. ( diaphragmatic hernia and eventeration are the common ones , but here diaphragm is seen in normal place . Other possibility of rapture is less likely as there is no trauma involved. 

This location pericardial cyst unlikely ( this large cyst anterior to heart 

So main DDs considered were a partially filled abscess inside parenchyma and pleural adhesions causing an appearance like this .
If it is parenchymal it must be in the lower lobe. 
If pleural it can either be in the front or back 
The line of diaphragm could be traced medially as there was a confusion whether this represented level of fluid. One more argument against abscess was the translucency of air ( above the fluid, if it is an abscess ) was not dark enough. 
So 
Repeat X ray AP and Lateral was taken 

So Now ?

There is no shadow in the lower lobe area as we postulated. The shadow in the mid zone represent the middle lobe consolidation. About the shadow we were considering is in the anterior part , and the level is clear , traceable beyond the diaphragm . It is a partially filled abscess. 
Rechecked for clinical findings in the same area. Normal resonance in percussion ,Normal intensity of vesicular  breath sounds ,normal resonance .

She remained a febrile ,active except for the fact that pus was draining 40 to 50 ml per day . Air was bubbling episodically . 
As there is possibility of bronchopleural fistula and lung expanded well we did nt ask her to inflate balloon which we used to do .
As she remained afebrile ,not sick not dyspnoeic same antibiotics were continued .We were curious from where this air and pus was coming as the X ray and USG did nt show any collection. As there was doubt whether there is chance of air entering to the tube from outside by accidental withdrawal , we checked for that also , and ensured ICD tube  has entered enough .The air column was moving free .

Two other things which came in to consideration

1. Should we instill streptokinase ?. We used to and had good results. In this case we did nt . Because there is bronchopleural fistula and we were afraid whether this will affect the sealing of fistula . 
2.Second point . Should we go for VATS. Yes . Many institutions resorts to early VATS and good results. Here in our institution it is being done, but not many cases and not for these young ones . We discussed with parents about the option to send to higher institution , but they opted to continue treatment here 

On the tenth day of ICD the bubbling was significant . 

There was argument for and against stepping up antibiotic . Consensus was to step up. 

What were the arguments for continuing same drugs . Kid is not sick , not febrile . Lung findings were not worsening ,xray and USG shows clearance. The shadow in the left side also does not need any intervention apart from what she is getting . 

Opposite view was..Patient is  already on ten days of antibiotics. Pus still coming , broncho-pleural fistula is there. Is it safe to continue first level antibiotics ?. Yes staph is always dangerous. ( One point forgot to mention that culture did nt yield growth )

We decided to step up 

Next question , stepping up to which one. Vancomycin ? Linezolid Clindamycin ? 

Vancomycin is superior for MRSA ,but inferior to cloxacillin or other antistaph agents if not MRSA .In this case chance for  MRSA is less. She responded very well to first line . Spectrum of action of vancomycin against other organisms less . 

Next choice was between Linezolid and clindamycin. Our experience with Linezolid for the last few years were excellent ,Good response most of the kids tolerating the drug very well . 

She was put on Linezolid 10 mg per kg per dose three times daily. Today fourth day of Linezolid. The air leak stopped completely, the pus drainage reduced. No pus yesterday. We were planning to remove the tube today . But today ten ml of pus still there. Now we decided to continue ICD for few more days . 

What are our plans now

1.First control present problem 

Next step to find out the reason behind , ie there is immunological basis . We are planning to do the immunoglobulin levels. We had hyper igE syndromes presenting like this. One of those cases now going well with long term co trimoxazol orally low dose .

If results are negative, may need to consider rarer entities. 

Shall let you know the follow up 

8/8/2016

On sunday she developed sudden dyspnea. Xray was taken and showed this 

ICD was blocked ,resulting in pyopneumothorax .ICD changed and distress releived . Fifty ml of pus drained . 

Linezolid stopped and she was put on Vancomycin and cefepime . 

Next day draining of pus almost nil but the air bubbling continued, with each breath .

In view of this CT was done 

;

Broncho pleural fistula . 

ICD was continued for three weeks. Gradually bubbling stopped . We could remove ICD ,patient afebrile , about to shift her to ward 

She developed sudden dyspnoea cyanosis

 Xray taken 

Again ICD was put 

This time her dyspnea did nt improved. Bubbling continued. 

We decided to surgical intervention . Patient opted for Surgery from Another institution 

20 , december 

Middle lobectomy done . 

Specimen 

Post surgery Xray 

She is doing fine now 

Child with abdominal distention

one and half year old female child was referred to us by her family doctor as he thought something wrong with her abdomen.

She was second kid born out of non consanguineous marriage ,elder one is five year old healthy boy .

No significant antenatal ,perinatal problems . 

Her development was normal in all fields till ten months when she started to stand holding furniture ,from there achievement was slowed down .

Now She can  walk holding on fingers which corresponding to one year. 

Her manipulation ,social development corresponds to one year and three months. 

In short there is mild delay in all fields , gross motor  a bit more involved. 

Parents took her to the family doctor when she developed running nose and fever and fever  subsided in three days with symptomatic measures. Parents did not notice anything wrong with her abdomen . They were a bit concerned with the developmental delay because the elder boy achieved all the milestones earlier than her 

No seizures ,no excessive irritability .

No history of any significant illness so far . 

No contact with tuberculosis. 

No history of travel outside .

O/E 

vitals stable .

No pallor 

No significant lymph nodes. No rashes, No bleeds .

GIT 

Oral cavity normal

Abdomen exam showed Liver 5 cm , span 10 cm firm ,sharp margins surface smooth surface

Spleen 12 cms ,crossing the mid line. Firm .Possibility of other masses ruled out as insinuation of fingers between costal margin not possible and bi manual palpation negative .

Genitals normal

Nervous system examination  

Cranial nerves all normal . Special stress on eyes. No squint ,no abnormal eye movements, Ocular movement in all directions full 

( fundus normal ,no cherry red spots or optic atrophy ) , 

Discussion

In short girl child one and half years with delay in milestones , with gross spleno hepatomegaly . 

Overall pattern of development she was normal up to nine months but there is slowing .Deciding about the development is one major decision

1.Is this delay significant or just a normal variation ?

2. Is it static type or Progressive type ? 

A bit difficult ,because we do see mild slowing of the previous pace of development following any acute illness. So may be this is just a normal situation 

But  few points need to be answered before we are happy with the above argument 

1. Was there a significant illness to account for this delay?

2. Of course  significant illness can cause some slowing or may be a dipping of the curve , and after a gap of few week catch up . But in this case it is more than three months since they noticed the dip 

3. We do get a dip or slowing following acute illness severe enough. But will it affect all the fields . Usually gross motor is the maximum affected. Here all the fields are affected . 

So in short pattern of development is more like a progressive disorder . But we dont have strong evidence for it as there is nothing suggestive of a definite grey or white matter involvement so far .

Once more a rethinking 

As the  development is affected and a gross spleen is there  bit of bias in our approach  that it is a neurological problem  . Did we jump to that conclusion without a second thought ?

Of course hard finding is significant spleno hepatomeglay in a young kid ? Other points are not strong enough. May be the basic entity responsible for the gross organomegaly cause bit of delay as part of its course eg a chronic infection .

So we ll take a deviant approach ignoring  the development part which is not a hard finding 

We ll take the dependable finding of gross spleno hepatomegaly here 

What are the main entities which cause this much of organomegaly at this age ?

1. Hemolytic anemia esp thalassemia 

2. Malaria 

3.Malignancy ,adult type of Chronic myeloid leukemia ,rarely NHL

4.Kala Azar 

5.Other hematological disorders like osteopetrosis, Myelofibrosis 

 She is not pale, so far no requirement of blood transfusion. 

There is no fever apart from short febrile illness lasting for two days which subsided

No weight loss 

These arguments argues against most of the above differentials. So this must be an entity causing significant enlargement of spleen and liver ,uniformly a bit firm in consistency ,without involving blood formation or causing blood element consumption . This is one entity not causing much of fever or inflammatory element .

Considering the above points revise the list again , excluding the above 

Storage disorder

Portal hypertension 

Portal hypertension without any features of liver function involvement and this huge spleen a bit unusual , not impossible .

 if we give significance to development problem storage disorder  is more likely.

Which one ? carbohydrate ?Lipid.? Others like Mucopolysacharide, mucolipidosis and many more . 

Here no features in the general examination supporting the last groups , 

Never patient had symptoms of hypoglycemia. But glycogen storage disorder may not have symptoms ,may present with hepatomegaly only . 

But spleen if at all is possible in Type 4 and it is due to portal hypertension ( reminding you , glycogen is not stored in spleen .Glycogen is stored in liver, muscles including heart , and kidneys Not in spleen . Spleen is involved in Type 4 not with storage but by portal hypertension ) This huge spleen is unlikely in portal hypertension .

Apart from this few of the general examination features which may be helpful when we consider storge of glycogen are the doll facies, and floppiness, large toungue etc. In this case none of them . 

So most likely not glycogen storage. 

Which one of lipid storage ? All of them can have liver and spleen enlargement . Main group are gangliosidosis 1 and 2, Spingolipidosis and cerebrosidosis 

Gangliosidosis Type I look like MPS and they ll have abnormal appearance and obvious features. Type II. Tay sachs wont cause organomegally , Sandoffs organomegaly possible but small . and onset late 

Neiman pick many verities are there  , most of them cause predominant liver involvement . Most of them significant functional disturbance esp type C . neurological involvement esp occular , gaze etc. more prominent. Of course fundus examination ll help as all  of them may have cherry red spots  . But it is not a must in early stages. 

Here none of the above descriptions fit with the clinical feature.

So what is remaining is Gauchers , adult type. 

Out of the two types. infantile type ( adult does nt mean it ll occur in older and vice versa ) will have severe neurological problems. Here except for a minimal delay neurological examination is normal 

So we considered the possibility of Gauchers 

So after the basic blood counts we decided to go ahead with a bone marrow examination 

We personally went to pathology department to discuss the problem and we wanted them to look for 

1.Leishmaniasis

2. Malarial parasite

3.Malignancy both CML , or NHL

4.Gauchers 

This is the Bone marrow picture 

( We thank Doctors in our Pathology department ,especially Dr.Feroz , HOD Pathology for giving us the slide )
Patient sent home this week 
We are planning an enzyme assay . The firm which markets the enzyme ll do the enzyme estimation free of charge. We have contacted them , and the tools for collection of sample awaited. 
One happy news .. 
Till recently cost of the enzyme replacement was around fourty lakh a year and no chance for a poor family to afford this for a lifetime . Last year one family filed a case and the verdict is favoring them , to support the cost by the govt. 
I reserve my comments about the court decision and the ethical issue involved . 
But we ll reveal the information to this family too .