N
Urgancı MD ¹, M Arapoglu MD ¹, B Akyıldız
MD2, A Aydın MD3
¹Clinic
of Paediatrics, Şişli Etfal Hospital, Istanbul, Turkey
²
Division of Paediatrics Intensive Care Unit, Department of Paediatrics,
University of Erciyes Kayseri, Turkey
³
Division of Paediatrics Metabolic Diseases, Department of Paediatrics,University
of Istanbul, Istanbul, Turkey
SMJ 2008 53(1): 60
Abstract
Familial chylomicronemia syndrome is a disease characterised by hypertriglyceridemia and chylomicronemia. In recent years, carnitine has been used in the treatment of hyperlipidemia and it is reported to be highly effective. We report a patient presenting with acute pancreatitis who through testing was diagnosed with familial chylomicronemia syndrome. We found the use of carnitine treatment in familial chylomicronemia syndrome to be highly effective.
Key words: Acute pancreatitis, carnitine, familial chylomicronemia syndrome
Introduction
Familial chylomicronemia syndrome may present with acute pancreatitis in childhood when triglyceride levels are greater than 1000 mg/dl. The syndrome may be caused by two different genetic defects: Lipoprotein lipase (LPL) deficiency and apoC-II deficiency.1 Characteristic lipoprotein distribution in the disease is the increase of triglyceride in fasting serum. Triglyceride levels of plasma are very high, usually between 2000-4000 mg/dl and can exceed 10000 mg/dl. Only one third of patients may present in the first year of life, the rest has no symptoms in infancy. Pancreatitis may develop in early infancy period.2,3 In recent years, have shown that L-carnitine could be highly effective in decreasing cholesterol and triglyceride levels in the treatment of hyperlipidemia.4-10 We present a case of a patient who was diagnosed with acute pancreatitis due to familial chylomicronemia syndrome and describe the role of carnitine as treatment.
Case Report
A two month old male baby was referred to our hospital with complaints of irritation, bilious vomiting and fever. His complaints started a few hours before admission. Gestational and neonatal history was unremarkable. Parents were first-degree relatives. They lost their first baby due to meconium aspiration and had a 3.5-year-old healthy boy.
In physical examination, weight and height were 5900 gr (75-90 percentile) and 60 cm (75-90 percentile), respectively. Fever was 38.5 °C rectal. The baby was tachypneic and tachycardic. The abdomen was tender and distended, intestinal sounds were diminished and liver was palpated 4 cm. The spleen was not palpable. No lesions or rush was seen on the skin. Bilious material was drained through the nasogastric tube.
Initial
laboratory investigations including a full blood count, renal function tests,
liver enzymes, bilirubins, total protein, blood glucose levels and urinalysis
were within normal limits. Serum sodium level was low (127 mmol/L), potassium
and chloride levels were normal. An abdominal X-ray revealed air-fluid levels.
Intestinal loops were dilated, the pancreas was oedematous, and hepatomegaly was
noticed in abdominal ultrasonography. Based on this evidence, the patient was
prepared for an emergency operation with the diagnosis of acute abdomen.
However, blood samples revealed that the serum had a milky appearance and thus,
the lipid profiles were assessed. Blood samples taken at 12 hours of fasting
were kept at +4˚C overnight and a cream-like layer was seen on the surface
of the serum. Results from the lipid tests showed that triglyceride
level was 7400 mg/dl, cholesterol 420 mg/dl, high-density
lipoprotein (HDL) level was 16 mg/dl (normal: 35-55 mg/dl), low-density
lipoprotein (LDL) level was 161 mg/dl (normal: 80-180 mg/dl), and very
low-density lipoprotein (VLDL) level was 1480 mg/dl (normal: 10-50 mg/dl).
Amylase level was 372 IU/L (0-50 IU/L); lipase level was 24 IU/L (0-10 IU/L),
which were consistent with acute pancreatitis. Plasma free fatty acids, insulin
and C-peptide levels were normal. On further investigation, the family history
revealed death of seven brothers of the father with similar symptoms. The lipid
profiles of the mother and the sibling were normal but the cholesterol and
triglyceride levels of the father were 155 mg/dl and 300 mg/dl, respectively.
From this evidence, the patient was diagnosed with familial chylomicronemia
syndrome and acute pancreatitis.
Treatment including total parenteral nutrition, antibiotics, H2 receptor blocker and carnitine 150 mg/kg was started. Basal carnitine level was normal. The clinical course ameliorated on the fourth day of treatment and oral alimentation was started. The serum amylase level was 59 IU/L, and levels of triglyceride, cholesterol and VLDL were 333 mg/dl, 287mg/dl and 86 mg/dl, respectively.
The
patient was breastfed and carnitine treatment 100 mg/kg was started. A liver
biopsy was performed to rule out intrahepatic cholestasis. Histological
examination showed swelling in parenchymal cells, and mononuclear cell
infiltration in portal vessels; however, steatosis was not marked. The lipid
profile of the case is shown in Table 1.
On
follow-up, the serum triglyceride levels were between 200-400 mg/dl. The patient
did not have any colicky abdominal pain or another pancreatitis attack. No
pancreatic calcifications were remarked in abdominal ultrasonography. When the
patient was 2.5 years old, the carnitine treatment was stopped by the family due
to financial reasons. The month following treatment end, triglyceride levels had
risen to 4000 mg/dl no symptoms were reported. Carnitine treatment was started
again. At this present time, the patient is 6 years old and there has been no
reported complications. His weight is 23 kg (75 percentile) and height is 120 cm
(75 percentile).
Discussion
Familial
chylomicronemia syndrome is a disease presenting with chylomicronemia and
triglyceridemia. The disease is characterised by recurrent colicky pain,
pancreatitis attack, hepatosplenomegaly, lipemia retinalis, eruptive cutaneous
xanthomas and inadequate increase in weight.1,11
The most common symptom at any age is recurrent abdominal pain which is
often colicky in nature and can mimic acute abdomen.1 Emesis,
vomiting, diarrhoea, anorexia, fever and leukocytosis may be seen during a
severe colicky pain attack.12 In
some cases it is the case that an acute abdomen can not be ruled out and
patients undergo operation.
13.
Our patient, who was brought with the complaints of irritation and bilious
vomiting would also have undergone an operation if the milky blood samples had not noticed.
Chylomicronemia syndrome occurs due to deficiency of LPL or
apolipoprotein C-II, which is a cofactor for LPL and Triglyceride levels exceed
1000mg/dl.11.
Levy et al
12 showed that in 30 % of 43 LPL deficiency cases,
clinical symptoms first manifest in the early infancy period. This was found in
our case, the patient presented with symptoms at two-months
and family history revealed similar cases. Unfortunately, we could not
study the LPL and apo-C-II activity and genetic analysis of the patient.
Hypertriglyceridemia
is a predisposing factor in development of acute pancreatitis. The mechanism of
pancreatitis is not clearly known but it might be due to increase of isolecitin
and fatty acids in pancreatic acinary cells hydrolyzing triglycerides and
phospholipids in pancreatic tissue.11
It has also been suggested that increased plasma viscosity might
deteriorate the microcirculation, which may lead to pancreatitis.14
In hyperlipidemia, since amylase levels might be normal, patients can mistakenly
undergo an operation.
14.
In our case, elevation of amylase and lipase levels facilitated our diagnosis of
acute pancreatitis.
When
patients with LPL enzyme deficiency are admitted to hospital with acute
pancreatitis, the first treatment should be symptomatic with the aim of reducing
chylomicrone production. A diet with a restriction on lipids is started. The use
of long chained fatty acids should be lowered to minimum so that patients remain
asymptomatic for longer periods and the recurrent abdominal pain attacks
diminish. Fasting triglyceride levels should be less than 1000 mg/dl for
asymptomatic periods; however, symptoms could be better controlled when
triglyceride levels are less than 500 mg/dl.
In
recent years, studies on carnitine, which is a very important cofactor in
transport of long chain fatty acids into mitochondria, have been carried out. 4-10,15,16
Carnitine plays a role in mitochondrial β-oxidation of long chain fatty
acids, increases lipid emulsion clearance and transport of achyl radicals.16
It has also been shown that carnitine increases the rate of fat oxidation in
liver.5 Maccari et al4 detected a decrease in serum
triglyceride and free fatty acid levels in mice fed with fatty diet for 15 hours
after the addition of L-carnitine to the diet.
Stefanutti et al. suggest that cholesterol levels decreased significantly
and apolipoprotein A level
was increased in patients given L-carnitine.6 In addition, when L-carnitine
was given to patients with increased plasma lipoprotein A levels, a significant
decrease in LDL-cholesterol and an increase in HDL-cholesterol were noticed.8,9
In our case, we started treatment with 150 mg/kg L-carnitine. The clinical
picture of our patient dramatically ameliorated within 24 hours and decreases in
cholesterol and triglyceride levels were detected on the third day of the
treatment. Consequently, L-carnitine 100 mg /kg was continued to maintain
triglyceride levels below 400 mg/dl. Except for the one-month period when the parents
stopped carnitine treatment, triglyceride levels did not exceed 1000 mg/dl even
in periods of infection and no recurrent colicky pain or pancreatitis attack was
seen.
Familial chylomicronemia syndrome should be kept in mind in patients admitted with severe colicky pain, bilious vomiting and acute pancreatitis. We observed that L-carnitine ameliorates the clinical picture, lowers and maintains triglyceride levels and decreases the frequency of acute pancreatitis in our patient. In our experience, we found the use of carnitine treatment in familial chylomicronemia syndrome to be highly effective.
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