1. Splenohepatomegaly- How do we approach?
Presenter:
Viral Shah - KEM Hospital, Mumbai
Moderator:
Seema Alam - Pediatric Hepatologist, ILBS, New Delhi
Panelists:
Priya Kishnani – Pediatrician & Geneticist,
Duke University, North Carolina, USA
Archana Kher – Pediatrician,
Columbia Asia, Pune
Manoj Ghoda – Gastroenterologist,
Gujarat Research & Med. Inst. Ahmd

2. Splenohepatomegaly How do we approach?
Dr Viral K Shah
Under guidance of
Dr Mamta N Muranjan
Genetic Clinic
Department of Pediatrics
Seth GSMC & KEM Hospital
Mumbai

3. _ 3 years 4 months female child
_ 5th degree consanguinity
_ Antenatal ,intranatal & postnatal uneventful.
_ FTND, APGAR normal, 3.25kg

4. Presenting Complaints
_Progressive upper abdominal distention
_Tonic posture of the neck (back arching) at
4 months, 1-2 episode.

5. We Also Asked For…
Feature
Jaundice
Present or not
-
Pallor with edema
Blood transfusion
Joint pain or deformity
Repeated infections
-
Bleeding from any site
Seizures, altered sensorium
-
Fractures

6. - Global developmental delay
- Developmental age 10-11 months

7. Summary
_ Progressive upper abdominal distension most likely
Organomegaly with Global delay

8. Examination
Anthropometry :
Vitals-Stable, within normal limits
Observed
Expected
Percentile
Length (cm)
78
81
15th *
Weight (kg)
9.8
10.2
15-50th *
Head
circumference
45.5
46.5
15-50th *
* WHO growth chart

9. General Examination
1) Pallor
2) Left eye: Convergent squint
3) No icterus,cyanosis,clubbing edema,
lymphadenopathy
4) There was absence of
_
Hemolytic / coarse facies
_
Bleeding manifestation
_
Bone tenderness or joint swelling
_
Signs of liver cell failure
• Old photo of face which
I emailed you

10. Abdomen: Examination
_ Distension, umbilicus displaced
downward
_ Liver: Firm, non-tender, smooth
surface
_ 6 cm below right mid clavicular line,
_ 5 cm in mid axillary line
_ Span 9 cm
_ Spleen: 14 cm below left costal
margin
_ No signs of ascites
_ All other systems are normal
including CNS

11. Clinical Diagnosis
without jaundice, without signs of liver cell failure in a
developmentally delayed child
1.5 years old child with splenohepatomegaly with pallor,

12. What are the Possibilities

13. Differential Diagnosis
•Storage disorder

14. Investigations
Liver functions
Hematology
Date (Age)
25/2/11
(15 months)
10.6
SGOT/SGPT
(U/L)
186/ 126
(10-45)
4700
7100
Alkaline
247
phosphatase (U/L) (125-340)
Platelets
1,50,000
1,32,000
GGT (U/L)
MCV/
MCHC
64.5/
33.9
57.92 /
30.2
30
(5-55)
Retic /
Correcte
d retic
2.1 / 1.4
Total protein/
Albumin (gm/dl)
6.6 /
3.8
Bilirubin (mg/dl)
0.28
PT/INR
13.5 / 1.05
Date (Age)
15/2/11
(6 months)
25/2/11
(15 months)
Hb/PCV
(gm/dl)
10.1
TLC

15. Investigations
_ Chest x ray : Normal, x-ray spine – D9 hemivertebra
_ Fundus examination : No cherry red spot
_ USG abdomen with doppler : Hepatosplenomegaly with
normal liver and spleen echotexture, no portal hypertension
_ Hemoglobin electrophoresis : Normal (Hb A-93.7, Hb F – 3.6,
HbA2 – 2.7) ruled out hematological disorder
_ Bone marrow : Reported as normal

16. What’s next?

17. Enzyme Studies
_ Leukocyte β-glucosidase : 3.7 (8-32 nmol/hr/mg protein)
(46 % of lower limit of normal)
_ Plasma Chitotriosidase : 4274.8 ( 28.66-62.94 nmol/hr/ml)
(69 times higher than normal)
_ Leukocyte Sphingomyelinase : 0.92 (0.77-2.33 nmol/hr/mg protein)
Possibility of Neuronopathic Gaucher disease (type 3)
(low B-glucosidase with relatively mild neurological impairment)
Child was referred to our Institute for enzyme replacement therapy for

18. However………
_ Anemia and thrombocytopenia was not progressive
_ On follow up hepatosplenomegaly was not
progressive
_ X – ray spine did not show typical features of
Gaucher disease
_ Gaucher cells were not observed in bone marrow

19. Further Evaluation
➢ Bone marrow repeated: No Gaucher cells but presence of
foamy macrophages
➢ Repeat Beta glucosidase activity:
3 (4-14)(75% of lower limiit of normal)
➢ Plasma Chitotriosidase level :
2879 (8-87)(33 times elevated)
➢ Genotyping: No GBA gene mutations

20. Bone Marrow Examination
Giemsa stain : Storage cells with foamy cytoplasm

21. Clinical Course
30 months of Age
➢
➢ Drooling of saliva
➢ Feeding difficulty: Coughing and choking
➢ Dysphagia
➢ Regression of mainly motor milestones (stopped cruising and
standing with support)
Progression of neurological disease

22. At 3 years of age
_
_ Present Hemoglobin – 11, Total count- 5080, platelets- 3.45 lakh
_ Bulbar palsy
_ Weight loss because of poor feeding due to dysphagia, on
nasogastric tube feed
_ Non-ambulatory
Anemia corrected with hematinics

23. Recent Photographs

26. Summary
_
_ Non-progressive pallor and splenohepatomegaly
_ Global developmental delay followed by motor regression
_ Non-paralytic squint
_ Foam cells on bone marrow
_ Mildly reduced level B-glucocerebrosidase activity and absence of
mutation of GBA gene
Early childhood onset of symptoms

27. Final Diagnosis
Pathogenic homozygous mutation in exon 8
Nucleotide change c.1211G>A
Amino acid change p.Arg404Gln
Final diagnosis:
Niemann-Pick disease type C

28. Take Home Message
_ Storage disorders can have overlapping clinical features
_ Discrepancies between clinical features, disease course
and investigations : Alert for alternative diagnosis
_ Mainstay of diagnosis : Genotype with or without
estimation of enzyme activity, bone marrow supportive
requires expertise for interpretation
_ Confirm diagnosis : Must for enzyme replacement
therapy as enzyme is disease specific

29. POSSIBILITIES
Saposin – C deficiency
Prosaposin deficiency
Niemann-Pick disease
type C

30. Metabolic Pathway of Gaucher Disease

31. Role of Prosaposin and Saposin C in Gaucher disease
Glucocerebrosidase(GCase)
binding to the membrane
and saposin-mediated
activation.
Saposin molecules are colored in
purple; lipid polar groups are blue

32. Possibilities
Possibility
Saposin – C deficiency
Prosaposin deficiency
Niemann-Pick disease type C

33. Possibilities
Possibility
Features favoring
Saposin – C deficiency
Clinical and histopathological features
of Gaucher disease and absence of
GBA gene mutation
Prosaposin deficiency
Niemann-Pick disease type C

34. Cholesterol Transport Defect in NP-C Cells

35. POSSIBPossibilitiesILITIES
Possibility
Features favoring
Saposin – C deficiency
Clinical and histopathological features
of Gaucher disease and absence of
GBA gene mutation
Prosaposin deficiency
Niemann-Pick disease type C

36. POSSIPossibilitiesBILITIES
Possibility
Features favoring
Saposin – C deficiency
Clinical and histopathological features
of Gaucher disease and absence of
GBA gene mutation
Prosaposin deficiency
Niemann-Pick disease type C
_
_
_
_
Progressive neurological disease
Foam cells in bone marrow
Normal sphingomyelinase activity
Mildly elevated chitotriosidase