dr swati- case of hepatomegaly
TRANSCRIPT
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