CASE REPORT

Case report

Siblings with hepatosplenomegaly and lipoprotein lipase deficiency

Jochen G Schneider, Susanne Schaefer, Bernhard Lettgen, Tanja Keiper, Peter P Nawroth, Klaus A Dugi A 2-year-old Turkish girl was brought to agarose gel. Presence of the restriction site the outpatient clinic in April, 1999, with resulted in fragments of 27 and 118 bp. loss of appetite. She weighed 89 kg, Interestingly, genetic analysis confirmed corresponding to the 3rd percentile for her homozygosity for the same LPL mutation age. Her abdomen was distended with in a newborn sibling of the patient who normal bowel sounds. We found palpable also presented with high triglycerides hepatosplenomegaly but no xanthomata (>228 mmol/L) and hepatosplenomegaly. nor lipaemia retinalis. Abdominal ultraThe expected obligate heterozygote status sound showed severe hepatosplenomegaly, of the parents was verified by genetic with a liver length of 113 cm in the analysis. We counselled the parents fronto-axillary line and a splenic volume of regarding an optimal diet, including the 260 mL. Her haemoglobin was 100 g/L. A use of medium chain triglyceride oil. After complete blood count, serum electrolytes, 6 months, we repeated the abdominal and urine analysis were normal. Liver ultrasonograph, and found a marked function tests were normal. We screened reduction in hepatosplenomegaly. When for viral causes of hepatitis, and measured last seen in April, 2001, the child still had serum -fetoprotein, ceruloplasmin, and raised plasma triglycerides, but had made -1 anti-trypsin. The child had increased physical gains, and progressed from the plasma triglycerides; 1002 mmol/L, total 3rd to the 25th percentile of weight cholesterol; 214 mmol/L, and low HDL for age. cholesterol; 023 mmol/L. A plasma sample activated recombinant lipoprotein Patients with primary LPL deficiency lipase (LPL), ruling out apoC-IImay present with hepatosplenomegaly deficiency as the cause of hyperand corresponding hypertriglyceridaemia, triglyceridaemia. We injected 60 U of The patient's first blood sample which is due to a massive accumulation heparin per kg of bodyweight to release (April, 1999) of chylomicrons in plasma, and poses lipoprotein lipase from the endothelium1 the danger of developing acute pancreatitis.3 In most cases, chylomicronaemia responds to and found complete LPL deficiency, and undetectable LPL protein by ELISA. dietary fat restriction and the dietary use of medium chain triglycerides. Hepatosplenomegaly may result To identify the molecular cause of the patients in an extensive work-up because of the serious hypertriglyceridaemia and hepatosplenomegaly, genomic implications of potential malignant or storage disease.4 DNA was purified in order to sequence the 9 coding exons Chylomicronaemia is a rare, but readily identifiable of the LPL gene, located on chromosome 8, by cycle cause of hepatosplenomegaly. Our patient, and her sequencing. The primers used to amplify the exons have brother, had a molecular defect in the LPL gene causing been previously reported.2 We identified a novel, chylomicronaemia and severe hepatosplenomegaly. However, simply noting the patients milky plasma at homozygous duplication of four base pairs after position her first venupuncture, and requesting a lipid profile 262 in exon 1 of the LPL gene. The duplication causes a should have been sufficient to diagnose and treat frame shift resulting in a STOP codon at position 295 in chylomicronaemia-induced hepatosplenomegaly. Such an exon 2 of the LPL gene. The mutation therefore results in observation is less expensive than an algorithm-based, a mature protein of only 13 aminoacids, compared to the extensive work-up including many laboratory tests, 448 aminoacids of wild type LPL. The presence of the heparin injections, and DNA analysis. identified mutation was confirmed by restriction digesting. Since the mutation does not result in a new restriction site, a mutagenic antisense primer was used to introduce a BsiE I recognition sequence in the presence of the mutation. References The expected length of the PCR product was 145 bp. The 1 Iverius PH, Brunzell JD. Human adipose tissue lipoprotein lipase: PCR products were digested with BsiE-I at 62C for 1 h in changes with feeding and relation to postheparin plasma enzyme. Am J Physiol 1985; 249 (1 Pt 1): E10714. a total volume of 50 L, and were analysed on a 2%
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Lancet 2002; 360: 1150

Department of Internal Medicine I (J G Schneider MD, T Keiper, P P Nawroth, K A Dugi MD), Heidelberg University, 69115 Heidelberg, Germany; and Darmstaedte Kinderkliniken (S Schaefer MD, B Lettgen MD) 64287 Darmstadt, Germany Correspondence to: Dr Klaus A Dugi (e-mail: Klaus.Dugi@med.uni-heidelberg.de)
3

Monsalve MV, Henderson H, Roederer G et al. A missense mutation at codon 188 of the human lipoprotein lipase gene is a frequent cause of lipoprotein lipase deficiency in persons of different ancestries. J Clin Invest 1990; 86: 72834. Brunzell JD, Deeb SS. Familial lipoprotein lipase deficiency, apo CII deficiency and hepatic lipase deficiency. In: Sciver CR, Beaudet AI, Sly WS, Vale D, eds. The Metabolic and Molecular Basis of Inherited Disease. 8th edn. New York: McGraw-Hill Book Co; 2000. 2789816. Wolf A, Lavine J. Hepatomegaly in neonates and children. Pediatr Rev 2000; 21: 30310.

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