Salla disease

Dr VISHAL H KACHHY

FELLOW IN NEONATAL MEDICINE

SYNERGY HOSPIAL, AHMEDABAD

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 upO/E: failure to thrive Mild Fullness of Abdomen Liver size- Just Palpable.(May be

considered Normal)• RS - WNL• CVS- WNL

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

DIAGNOSIS

Neonatal Hepatitis(Viral markers- Negative)

Supportive Treatment was started and advise to follow up

after one weekOne 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.

FURTHER INVESTIGATION

• S. Ammonia- Raised

• Urine for Routein Biochemestry - Normal

• Total plasma galactose - Normal

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

• LFT showed hepatocellular damage, both PT and ammonia showed worsening trend.

RFT, Electrolytes were normal

Patient was sent for further opinion.

• 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

Differential diagnosis ?

How will you proceed now

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

Neonatal Ascites(Cont):

– Hepatorenal Tyrosinemia type-I

– Neonatal Hemochromatosis

– Carbohydrate Deficient Glycoprotein Syndrome.

• Urinary ascites.

• Biliary ascites.

• Chylous ascites.

• Cardiac ascites.

Ascites(Cont):

In older children, due to       Trauma,       Infection, particularly tuberculosis,         Hepatocellular disease,          Pancreatic ascites,          Gynecologic,          GI abnormalities,         Neoplasia, and other miscellaneous causes.

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

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.

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).

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.

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.

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

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.

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.

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).

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,

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

Common Metabolic liver diseases of the newborn(Cont)

• Neonatal Hemochromatosis:

Severe hepatocellular dysfunction,

High ferritin and

High transferrin saturation.

Any Lead to Diagnosis?

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.

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

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.      

• 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.

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.

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