Annals of Diagnostic Paediatric Pathology

Annals of Diagnostic Paediatric Pathology 2004, 8(3-4):
© Copyright by Polish Paediatric Pathology Society
Pathology of fatty liver in children with LCHAD deficiency
Katarzyna Iwanicka 1 , Janusz Ksi¹¿yk 2 , Monika Pohorecka 3 , Maciej Pronicki 1
Annals of
Diagnostic
Paediatric
Pathology
1
Department of Pathology,
2
The Clinic of Pediatrics,
3
Department of Metabolic Diseases,
The Children’s Memorial Health Institute,
Warsaw, Poland
Abstract
Deficiency of long chain 3-hydroksyacyl-CoA dehydrogenase (LCHADD) impairs the process of mitochondrial
beta-oxidation of fatty acids. LCHADD may be clinically benign up to the moment of first symptoms,
i.e. fasting inducing the first acute life-threatening episode (ALTE). Patients present vomiting, lethargy, convulsions,
arrhytmia and hypoketotic hypoglycemia, which is essential for established a diagnosis. Thus, after
fasting, healthy looking child may die with serious symptoms of acute illness. The aim of this study was the
histopathological assessment of liver in our own LCHADD patients with particular attention to characteristic
changes including intensity, type and localization of liver steatosis. Seven liver samples were assessed: 3
biopsies and 4 autopsy specimens obtained from 6 patients, aged from 3 months to one year. In 3 autopsies
we found severe macrovacuolar fatty liver, in one biopsy moderate mixed steatosis, and in remaining 3 cases
mild fatty liver of macrovacuolar and mixed character. All samples but one displayed diffuse distribution of
steatotic hepatocytes. In 4 cases steatosis was accompanied by fibrosis and cirrhosis, in 3 by inflammatory
infiltrates. Intensity of steatosis was related to the severity of clinical symptoms. Fibrosis was another morphological
feature characteristic for LCHAD deficiency. The results showed that liver steatosis found during
autopsy of patients who died of unexplained reason should attract attention to LCHADD as a possible cause
of death.
Key words: LCHAD deficiency, liver steatosis
Introduction
Clinical symptoms of long chain 3-hydroksyacyl-CoA dehydrogenase
(LCHAD) deficiency usually appear after prolonged
fasting or could be evoked by upper respiratory tract infections,
vaccination, physical exercises and other stress. Clinically
healthy child presents hypoketotic hypoglycemia, which
may be accompanied by vomiting, abdominal pain, convulsion,
muscle weakness and cardiomegaly. In the course of the
disease sensorimotor neuropathy and pigmentary retinopathy
develop [5, 9, 11]. The age of onset ranges from one day to 40
months. Treatment involves the diet with long chain fatty acids
restriction and increased supply of carbohydrates.
Fatty acids are the most important source of energy
during fasting [5, 11]. They are transported into the inner
membrane of mitochondria to be used in beta-oxidation process
[5, 9, 11]. This process has especially important value
for muscle, heart and liver cells as their own source of energy.
Beta-oxidation process has two steps: transport and following
oxidation. Three enzymes take parts in transport of fatty
acids into the mitochondria, creating the pathway called carnitine
transporting system [2, 3, 5, 12]. Proper beta-oxidation
pathway depends on activity of several enzymes (four for long,
four of medium and four for short chain fatty acids). The names
of appropriate enzymes differ only by the name of length of
the chain. The basis of beta-oxidation process is shortening of
fatty acid chain by cutting acetyl-CoA to introduce it to tricarboxylic
acids cycle. Deficiency of 3-hydroksyacyl-CoA dehydrogenase
(LCHAD) impairs the process and leads to toxic
accumulation of fatty acids and their acylcarnitines derivatives
[2, 5, 7, 9, 11]. Accumulation of lipids in the cells may
be a site effect of this metabolic decompensation.
Address for correspondence
Iwanicka Katarzyna
Department of Pathology
The Children's Memorial Health Institute
Aleja Dzieci Polskich 20,
04-736 Warsaw, Poland
Phone: +48 22 815 16 14
E-mail: kasiai@yahoo.com