APPROACH TO A CHILD WITH HEPATOMEGALY

Guided by: Dr Manoj Ghoda Dr K.M. Mehariya Dr Chirag Shah Dr Charul Purani

CASE HISTORY

A three years old first order female child

Born out of 2nd degree consanguineous marriage

Presented at 4 months, at another hospital, with chief complaints of

Convulsions

Gradual distension of abdomen; which was found to be due to huge liver

Huge hepatomegaly without splenomegaly was the only relevant finding on examination

Hypoglycemia, blood sugar 40 mg/dl

Hemogram, Renal function tests and Liver function tests normal

Subsequently she had 8-10 admissions for severe metabolic acidosis, with hypoglycaemia

Liver biopsy done

Parents wished to have second opinion at CHA; so the patient was brought to us

No history of:◦Fever, vomiting, diarrhoea

◦Altered sensorium

◦Breathlessness

◦Jaundice, edema

◦Change in bowel pattern , weight loss

Birth history:◦Full term, normal delivered

Development history :◦Sat without support at the age of 1 year

◦Walked unassisted at the age of 2 years

On examination:◦Weight : 14 kg; Height: 84 cm (< 3rd percentile)

◦Doll like face, protuberant abdomen◦No pallor, cyanosis, clubbing, lymphadenopathy, icterus

◦P/A: huge hepatomegaly almost reaching right lower quadrant; no splenomegaly

◦CNS: Normal muscle tone and power, normal deep tendon reflexes

◦Other systems: NAD

◦Fundus : NAD

Attending paediatrician may have following questions:

Differential diagnosis?

Is this is a routine chronic liver disease?

Am I dealing with GSD or fatty oxidation disorder where we get hypoglycaemia, Hepatomegaly, and metabolic acidosis

How will I explain acidosis?

What is my diagnosis here?

How should I investigate this case further?

Let me examine him fully before I can say that this person is dead !!

APPROACH TO A CHILD WITH HEPATOMEGALY

First be sure it is hepatomegaly and

not a pushed down liver !!!!Always assess Liver span

ConsistencySurface

PHYSICAL ASSESSMENT OF HEPATOMEGALY IN

CHILDRENAge Acceptable

span ( cm )

Pre term infants 4-5

Healthy term infants 5-6.5

1-5 years 6-7

5-10 years 7-9

10-16 years 8-10

APPROACH TO A CHILD WITH HEPATOMEGALY

Size of the liver

Age of the patient at time of presentation

Presenting symptoms; presence of metabolic symptoms

Other system involvement

Liver damage: Hepatocellular, cholestasis, none

APPROACH TO A CHILD WITH HEPATOMEGALY

For example; in this particular case one may just consider SIZE of the liver which was huge.

Very limited causes of huge hepatomegaly at this age.

Most likely is some kind of storage disorder; GSD, LSD or stretching a little bit FAOD.

APPROACH TO A CHILD WITH HEPATOMEGALY

Presence of hypoglycemia and severe metabolic acidosis will further reduce the differential diagnosis to GSD and FAOD

APPROACH TO A CHILD WITH HEPATOMEGALY

On the other hand, if size of the liver is moderate or mild, differential diagnoses could be altogether different.

Since there could be many causes to consider; good history and physical examinaton are very essential

APPROACH TO A CHILD WITH HEPATOMEGALY

Neonatal age group

◦Pregnancy related

◦Structural

◦Metabolic

◦Idiopathic

APPROACH TO A CHILD WITH HEPATOMEGALY

Paediatric age group

◦Infective

◦Metabolic

◦Storage

◦Structural

HISTORY IN EVALUATING A CHILD WITH

HEPATOMEGALY Acute presentation

◦Any recent infection, fever, abdominal pain?

◦Drug or toxin ingestion?

◦History of recent travel?

◦Keep in mind that Wilson’s disease could have an acute presentation.

◦Chronic liver disease may have acute decompensation

APPROACH TO A CHILD WITH HEPATOMEGALY

Chronic presentation◦Is there a significant family history ?

◦Are there any metabolic complications ?

◦Is there any FTT

◦Any evidence of liver cell dysfunction?

◦Any evidence of portal hypertension ?

Hepatomegaly with nonspecific symptoms of fever, malaise, nausea, abdominal discomfort:◦Infective aetiology likely

◦Acute or chronic hepatitis

◦Drug induced hepatitis

◦Autoimmune hepatitis

◦Wilson disease

◦Alpha one antitrypsin deficiency

Hepatomegaly with prominent or recurrent vomiting ± altered sensorium :

◦Metabolic disorders

◦Reye’s syndrome

◦Fulminant hepatic failure

◦Hypervitaminosis A

Hepatomegaly with neurological deterioration OR loss of developmental milestones OR hypotonia:

◦Glycogen storage disorders

◦Lysosomal storage disorders

◦Peroxisomal disorders

◦MPS

Hepatomegaly with neurologic or psychiatric symtoms :

◦Wilson disease

◦Porphyrias

◦Urea cycle disorders

◦Drug toxicity

HELPFUL PHYSICAL SIGNS IN EVALUATION OF

HEPATOMEGALY Cataract : Galactosemia

Microcephaly : Congenital TORCH infections

Neuromuscular abnormalities in form of tremors or flaccidity : Lipid storage disorder

Pruritis : Cholestasis

Contd...

Asymmetric liver : Tumour, cyst, abscess

Rock hard hepatomegaly : cirrhosis, tumour

Coarse facial features : MPS

Mongoloid facies : Zellweger syndrome

Contd...

Enlarged kidneys : Polycystic disease, GSD, Tyrosinemia

Arthritis with erythema nodosum : Inflammatory Bowel Disease

Hemangioma : Hemangiomatosis of liver

KF ring : Wilson disease

Hepatomegaly with splenomegaly with anemia

◦Infections

◦Haematological

◦Malignancy

◦Metabolic

◦Collagen vascular disease

Hepatomegaly with splenomegaly, jaundice and anemia :

◦Infective :Malaria, kala azar

◦Hematological

◦Wilson disease

Isolated hepatomegaly w/o associated features mentioned above:

◦Hepatic tumors ( h/o weight loss)

◦Choledochal cyst

◦Caroli disease

◦Hepatic outflow obstruction: Budd- Chiari syndrome

◦Niemann-Pick type B

APPROACH TO A CHILD WITH HEPATOMEGALY

CONTD..... Other system involvement

◦Congestive cardiac failure◦Any systemic infection◦Haematological disorder◦Collagen vascular disease or Autoimmune disease

◦Inflammatory bowel disease◦Cystic fibrosis◦Sarcoidosis

RULE OF THUMB ???

Huge hepatomegaly with preserved liver functions suggests

◦storage disorder; at any age; or

◦Reticuloendothelial hyperplasia

INVESTIGATIONS

Remember!!

Good history, aided by meticulous examination will give clue to the underlying cause, more than any single investigation

Let me see if I can find out what is wrong with you!!

INVESTIGATIONS

Minimum◦Complete blood counts

◦Liver function tests including serum proteins

◦Prothrombin time

◦Hepatitis B serology

◦Abdominal USG

INVESTIGATIONS As and when required:

◦Serology for Hepatitis A-E◦Work up for infections like typhoid, TB

◦Serum ceruloplasmin,24 hour urinary copper, K.F. ring

◦Ferritin ◦ANA, anti SMA, anti LKM1◦Metabolic work up and specific testing for peroxisomal and lysosomal storage disorders

◦Liver biopsy

BACK TO OUR CASE

Key points in history and examination

Investigations :◦Hb: 9.6 Total count:7620

◦Platelet count: 4.1 lakh◦RFTs: normal ◦LFTs ( SGPT, S.Protein, PT, S.Bil ): normal

◦ABGA: normal RBS: 88

◦S.Cholesterol: 304

◦S.Uric acid: 10.81

◦Triglycerides: 1320

◦USG Abdomen: Hepatomegaly

◦Fundus: normal

◦Liver biopsy : marked elevation of glycogen in hepatocytes.

Liver biopsy showing mosaic pattern, prominent cell membranes and nuclear hyperglycogenation (HE stain); Distended hepatocytes without fibrosis

FINAL DIAGNOSIS

GLYCOGEN STORAGE DISORDER

TYPE 1

I = liver, Kidney, intestine

II = Heart, Muscle

III, V, VII = Muscle

IV = Cirrhosis

GSD

Glucose

Breakdown of

hepatic glycogen

Dietary glucose

Gluco-neogenesis from amino acids

Muscle glycogen

during exercise

rapid

time

GLYCOGEN STORAGE DISORDER TYPE I

( VON GIERKE’S DISEASE ) Autosomal recessive

Ia : Glucose-6-phosphatase deficiency (17q21)

Ib : Translocase deficiency (11q23)

Fasting hypoglycemia

CLINICAL FEATURES 3-4 months / may present in neonatal period

Doll like facies, short stature, hepatomegaly, renomegaly

Spleen and heart normal

Biochemical hallmarks◦Hypoglycemia, lactic acidosis, hyperuricemia, hyperlipidemia

UNDERSTANDING TYPE I AND TYPE III

Type I Type III Failure of

gluconeogenesis & glycogenolysis.

Deficiency of Glucose-6-phosphatase

no formation of glucose either from glycogen or from other sugars.

Failure of glycogenolysis.

Deficiency of Debrancher enzyme

Formation of glucose from other sugars is normal

FEATURE TYPE III TYPE I

Hypoglycemia + severe

Bleeding diathesis _ +

Splenomegaly ± _

Enlarged kidneys _ +

Myopathy + _

Elevated creatine kinases & transaminases ++ _

Fasting ketogenesis ++ +

Lactic acidemia _ +

Alanine in plasma low high

Hyperuricemia _ +

Little or no response to glucagon after fast + +

Normal post prandial response to glucagon + _

Increase in blood glucose after galactose,fructose + _

FURTHER INVESTIGATIONS

Enzyme studies

Molecular studies

Glucagon studies

Lactic acidosis

Hyperuricemia leading to tophaceous gout

Hypertriglyceridemia leading to pancreatitis and xanthoma

Nose bleed and petechiae due to platelet dysfunction

OTHER PROMINENT FEATURES

LONG TERM COMPLICATIONS OF TYPE 1 GSD

Hepatic Adenomas ( 2nd/3rd decade )

Polycystic ovaries ( fertility normal )

Renal disease, ESRD

Osteopenia

Pulmonary hypertension

MANAGEMENT Dietary advice: Uncooked corn starch meal◦< 2 yrs : 1.6 gm/kg every 4 hrs◦> 2 yrs : 1.75-2.5 gm/kg body weight

every 6 hrs

Calcium and Vitamin D supplementation

Allopurinol for hyperuricemia

Role of ACE inhibitors

Statins or Fibrate for hyperlipidemia

Orthotopic liver transplantation

Genetic counselling◦Carrier detection and prenatal diagnosis possible with DNA based diagnosis

MANAGEMENT CONTD...

PROGNOSIS

Guarded

Early diagnosis and effective treatment have improved the outcome

Renal disease and formation of hepatic adenomas with potential risk for malignant transformation remain serious complications.

THANK YOU