A 3 month old child presented with neonatal hepatitis and ascites. Initial tests showed liver damage and worsening liver function. Further testing found very high levels of sialic acid in the urine, suggesting Salla disease. Salla disease is a rare lysosomal storage disorder caused by a defect in sialic acid metabolism, characterized by ascites and liver involvement. The child was treated supportively but died from complications within two weeks.

1. Dr VISHAL H KACHHY
FELLOW IN NEONATAL
MEDICINE
SYNERGY HOSPIAL,
AHMEDABAD

2. 3 Month old child referred for neonatal
Hepatitis .
First child
Born out of non consanguineous marriage.
Birth weight was 2.1kg(Low) and on
regular follow up
O/E: failure to thrive
Mild Fullness of Abdomen
Liver size- Just Palpable.(May be
considered Normal)
• RS - WNL
• CVS- WNL

3. INVESTIGATION
• CBC
Hb:12.1; TC:8900 ,DC:65/35/2/2
Platelet:3.25
• CRP-0.8 ( Neg)
• SGPT-112
• PT -17/13
• S. Bil – T- 4.2
D-2.2
I-2.0

4. DIAGNOSIS
Neonatal Hepatitis
(Viral markers- Negative)
Supportive Treatment was started and advise to follow up
after one week
One week on,jaundice- persistent; there was no
appreciable change in SGPT and PT and now there was
some abdominal distention due to ascites.
Liver and Spleen was just palpable,
CNS, CVS and RS were all normal.

5. FURTHER INVESTIGATION
• S. Ammonia- Raised
• Urine for Routein Biochemestry - Normal
• Total plasma galactose - Normal

6. The child appeared well but there was a failure
to thrive with his weight actually showing
progressive decreasing trend.
Now the ascites had increased. So small
dose of diuretics was added
Investigation were repeated

7. • LFT showed hepatocellular damage, both PT
and ammonia showed worsening trend.
RFT, Electrolytes were normal
Patient was sent for further opinion.

8. • USG Moderate ascites and mild hepato-
spleenomegaly
• Serum albumin: ascitic fluid albumin
gradient was less than 0.8
• Bilirubin 15 mg with 70% direct,
• SGPT - 762, ALP was 308
• PT was 27/14 sec.
• Ammonia was 131,
• Creatinine 1.4 mg.
• S.ferritin, S. alpha fetoprotein- Normal

9. Differential diagnosis ?
How will you proceed now

10. Neonatal Ascites:
.
• Fetal or neonatal ascites is rare and occurs in
about 1:3000 pregnancies
Common causes include
• Metabolic diseases.
– Lysosomal storage disorders like,
• Salla disease
• Mucolipidosis type-II
• Niemann-Pick type-C
• MPS type-VII
• GMI galgliosidosis
• Wolman’s disease
• Gaucher’s diseases

11. Neonatal Ascites(Cont):
– Hepatorenal Tyrosinemia type-I
– Neonatal Hemochromatosis
– Carbohydrate Deficient Glycoprotein Syndrome.
• Urinary ascites.
• Biliary ascites.
• Chylous ascites.
• Cardiac ascites.

12. Ascites(Cont):
In older children, due to
Trauma,
Infection, particularly tuberculosis,
Hepatocellular disease,
Pancreatic ascites,
Gynecologic,
GI abnormalities,
Neoplasia,
and other miscellaneous causes.

13. Biliary Ascites:
• Rare in Neonates.
• occurs in infants younger than 3 months.
• Hepatobiliary isotope scanning demonstrates radionuclide in
the peritoneal cavity.
• Ultrasonography is usually necessary to rule out congenital
anomalies and obstructing lesions.
• Paracentesis reveals elevated bilirubin levels in the fluid. .
• The perforation usually seals in a few weeks in the absence
of obstruction or else it requires surgical intervention

14. Chylous Ascites
• Most cases occur in infancy, with a male
predominance,
• The diagnosis is confirmed with paracentesis;
markedly elevated triglyceride content (>1500
mg/dL) and a predominance of lymphocytes
(>75%).
• After surgical causes, eg, malrotation, obstruction,
and neoplasia) have been ruled out with
appropriate imaging studies, more than one half of
patients respond to conservative treatment with
parenteral nutrition and bowel rest for 2-4 weeks.
• Idiopathic neonatal chylous ascites is associated
with a high mortality rate.

15. Hepatocellular Diseases
• Storage disease, neonatal or viral hepatitis,
alpha1-antitrypsin deficiency,Hemochomatosis
• Paracentesis reveals the presence of fluid with
a serum-to-ascites albumin gradient (<1.1
g/dL).

16. Peritoneal infection:
• Appendicitis is common in
patients in developed countries,
whereas tuberculous fluid
collections and Salmonella
organisms are observed in
patients in the developing
world.

17. Pancreatic Ascites
• Either from trauma or pancreatitis.
• Paracentesis reveals fluid with markedly
elevated amylase and lipase levels
• Bowel rest and TPN are the initial therapies,
with the administration of somatostatin
analogs.

18. Iatrogenic ascites:
• Ascites may occur (particularly while the
patient is in the neonatal intensive care unit
[NICU]) as a result of gastric perforation from
gastric catheters.
• Umbilical catheter perforation may result in
the leakage of parenteral nutrition fluid

19. Some useful clues for diagnosis:
• If a large bladder is present, the ascites is probably
urinary.
• If vomiting occurs or bowel loops are abnormal
even though not distended, gastrointestinal causes are
likely.
• If there is impressive peripheral or body wall
edema, consider infection, heart disease, liver disease,
erythroblastosis, and other causes of hydrops fetalis
• If hepatomegaly is present, metabolic causes of
liver diseases are most likely.

20. Rapid liver failure in a neonatal jaundice is
almost always secondary to metabolic
disorders.
Infection or structural diseases take a
longer time to produce liver failure.

21. Common Metabolic liver
diseases of the newborn:
• Galactosemia:
Hyperbilirubinemia,(initially even
unconjugated),
Hemolytic anemia,
Sepsis, especially with E. coli.
Cataract (not very common in Indian neonatal
population).

22. Common Metabolic liver
diseases of the newborn(Cont)
• Hepatorenal Tyrosinemia:
High Plasma tyrosine levels and urinary
succinyl acetone, very high alpha fetoprotein
and marked coagulopathy.
• Hereditary Fructose Intolerance (HFI):
Lactic acidosis, hypoglycemia, hyperuricemia.
Menifest after introduction of fructose;
presence of reducing substances in the urine,

23. Common Metabolic liver
diseases of the newborn(Cont)
• Glycogen Storage Diseases type-IV:
Cirrhosis early in the disease,prominent
hypoglycemia, and myopathy.
• Peroxisomal Disorders and Mitochondrial
Disorders: : Developmental delay, failure to
thrive, seizures, hypotonia.Multi System
Disease

24. Common Metabolic liver diseases
of the newborn(Cont)
• Neonatal Hemochromatosis:
Severe hepatocellular dysfunction,
High ferritin and
High transferrin saturation.

25. Any Lead to Diagnosis?

26. Storage Disease
TMS blood sent- Normal
Urine was screened for metabolic disorders.
Sialic acid level in urine was measured and it
was 30 times the normal, suggesting sialic
aciduria or Salla disease.

27. Patient was treated with diuretics and
supportive treatment for liver failure; but had
convulsions and GI bleed and died within a
fortnight.

28. Salla disease
• Refers to LSD first reported in a geographically
restricted area in northern Finland.
• The enzyme defect in this condition has not been well
documented as yet.
• Defect in gene SLC17A5 located on chromosome 6
• Increased levels of free neuraminic acid are found in
the urine.
• Abdominal distension due to varying amounts of
ascites and hepatosplenomegaly may be the presenting
feature.
• The cause for ascites is obscure.

29. • Sialic acid storage disease
- Autosomal Reccesive disorder that
primarily affects the nervous system.
- Signs and symptoms that may vary widely in
severity.
- Classified into one of three forms:
* Infantile free sialic acid storage disease,
* Salla disease, and
*Intermediate severe Salla disease.

30. Infantile Free Sialic Acid Storage Disease (ISSD)
The most severe form of this disorder. Babies
with this condition have severe developmental delay,
hypotonia, and failure to thrive coarse facial features
seizures, bone malformations, hepatosplenomegaly and
rarely cardiomegaly. Affected infants may have a
condition called hydrops fetalis
Children with this severe form of the condition
usually live only into early childhood.

31. The Diagnosis can be confirmed by
• Characteristic histological findings on light
and electron microscopy
• Characteristic cellular enzyme defects and
• Urinary excretory products in these patients.
No spacific treatment is avilable, only
supportive and symptomatic treatment directed
towards complication