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 atCHA; 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, lymphadenopa thy, 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
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?
APPROACH TO A CHILD WITH HEPATOMEGALY Let me examine him fully before I can say that this person is dead !!
First be sure it ishepatomegaly andnot a pushed down liver !!!! Always assess Liver span Consistency Surface
Acceptable span Age ( cm ) Pre term 4-5 infantsHealthy term 5-6.5 infants 1-5 years 6-75-10 years 7-910-16 years 8-10
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
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.
Presence of hypoglycemia and severe metabolic acidosis will further reduce the differential diagnosis to GSD and FAOD
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
Neonatal age group ◦ Pregnancy related ◦ Structural ◦ Metabolic ◦ Idiopathic
Paediatric age group ◦ Infective ◦ Metabolic ◦ Storage ◦ Structural
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
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
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
Cataract : Galactosemia Microcephaly : Congenital TORCH infections Neuromuscular abnormalities in form of tremors or flaccidity : Lipid storage disorder Pruritis : Cholestasis
Asymmetric liver : Tumour, cyst, abscess Rock hard hepatomegaly : cirrhosis, tumour Coarse facial features : MPS Mongoloid facies : Zellweger syndrome
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
Other system involvement ◦ Congestive cardiac failure ◦ Any systemic infection ◦ Haematological disorder ◦ Collagen vascular disease or Autoimmune disease ◦ Inflammatory bowel disease ◦ Cystic fibrosis ◦ Sarcoidosis
Huge hepatomegaly with preserved liver functions suggests ◦ storage disorder; at any age; or ◦ Reticuloendothelial hyperplasia
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!!
Minimum ◦ Complete blood counts ◦ Liver function tests including serum proteins ◦ Prothrombin time ◦ Hepatitis B serology ◦ Abdominal USG
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
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
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
Type I Type III Failure of Failure of gluconeogenesis & glycogenolysis. glycogenolysis. Deficiency of Deficiency of Glucose-6- Debrancher enzyme phosphatase Formation of no formation of glucose from other glucose either from glycogen or from sugars is normal other sugars.
FEATURE TYPE III TYPE IHypoglycemia + severeBleeding diathesis _ +Splenomegaly ± _Enlarged kidneys _ +Myopathy + _Elevated creatine kinases & ++ _transaminasesFasting ketogenesis ++ +Lactic acidemia _ +Alanine in plasma low highHyperuricemia _ +Little or no response to glucagon + +after fastNormal post prandial response to + _glucagonIncrease in blood glucose after + _galactose,fructose
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
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.