Annals of Diagnostic Paediatric Pathology

90
Since 1994, twenty two unrelated children with LCHAD deficiency
have been identified in Poland. Diagnosis was done
on the analysis of GC-MS organic acid profile in urine and
than confirmed by genetic investigation. Common protocol
of treatment and monitoring (CPTM) has been introduced in
2000. There were 8 LCHAD-deficient children identified before
CPTM. Diagnosis was markedly delayed in all cases,
rarely established at first acute life-threatening episode
(ALTE), frequently post mortem. Five of them died, only three
patients were in good condition. In second period (since 2000)
14 new LCHAD deficient cases were identified. The diagnosis
was established usually at first ALTE, only in 4 patients
too late (post mortem or post-episodic neurological sequels).
As in the literature there are only few reports concerning
histological pattern of the liver from patients with LCHAD
deficiency [5, 7, 9, 11], the aim of our study was to analyse
morphological findings in the liver of 6 patients with LCHAD
deficiency to establish the spectrum of morphological changes
and compare our results with the described reports.
Results
Case No 1
The liver specimen has been obtained on autopsy. It revealed
the diffused localization of mixed pattern of steatosis concerning
of 100 % of hepatocytes. Apart of congection any
other pathological change was not detected in the liver. Steatosis
of cardiomyocytes and lipid accumulation in renal proximal
tubules was observed as well (Fig. 1).
Material and methods
Material consists of seven liver samples obtained from six
LCHAD deficient patients (4 boys and 2 girls). One of the
patients underwent liver biopsy at the age of 3 months and
post mortem examination at 6 months. There were three biopsy
samples obtained from the LCHAD-deficient boys and
four autopsy specimens derived from affected patients (two
boys and two girls). Patients were aged from 3 to 12 months.
Clinical diagnosis of LCHAD deficiency was based on urine
organic acid profile analysis using GC-MS method (Dept of
Laboratory Diagnostics, CMHI), and confirmed by molecular
study.
The liver samples obtained during biopsies were prepared
for light and electron microscopy. Slides were stained
with hematoxylin and eosin, PAS, diastase digested PAS, for
collagen and reticulin fibres – AZAN and Gomori stains, respectively.
Semi-thin slides of plastic embedded (epon) liver
samples post fixed in osmium tetroxide and stained with toluidine
blue were used for steatosis detection. Liver tissue samples
obtained during autopsies were processed routinely for histology
and stained with hematoxylin and eosin.
During microscopical assessment we assumed three
grades of steatosis intensity: mild, moderate and severe, when
lipid droplets comprised up to 30%, 30-70%, and over 70%
of liver parenchyma, respectively. Two types of distribution
of steatotic hepatocytes were recorded: diffuse or focal. Type
of steatosis included three categories: macrovacuolar,
microvacuolar, and mixed. Semi-thin slides are very helpful
in correct lipid detection, especially of microvacuolar type.
Accompanying inflammatory infiltrates and fibrosis were assessed
according to routine grading and staging system.
Fig. 1 Liver biopsy of patient no 1 reveals severe mixed steatosis. Presence
of lipid accumulation in renal proximal tubules (of patient no 1).
Case No 2
The liver specimen has been obtained on autopsy. It revealed
the typical pattern of fatty liver. Macrovesicular lipid droplets
are present in almost all hepatocytes. Mild fibrosis was present
only in periportal areas. Inflammatory infiltrates and
cholestasis were not detected. There was found vacuolisation
corresponding probably to lipid accumulation in proximal renal
tubules (Fig. 2).