An Unusual Case of Severe Hypertriglyceridemia and Splenomegaly

Abstract

A 49-year-old man of Japanese and British ancestry was referred to a metabolic diseases clinic for evaluation 5 months after nontraumatic spleen rupture requiring splenectomy. Prior history included hypertension and mild frontal headaches, but no other neurological or cardiovascular symptoms. The patient did not smoke and used alcohol infrequently. His mother had coronary artery disease, and his father had mild hypertension. There was no family history of consanguinity, splenomegaly, diabetes, or developmental delay. The ruptured spleen weighed 727 g, and splenomegaly was associated with marked sinus histiocytosis spreading apart the lymphoid component. The overwhelming majority of histiocytes were foamy (Fig. 1a⇓ ), and only a few had sea-blue appearance and reacted positively with periodic acid-Schiff (PAS), PAS and diastase, and May-Giemsa stains. A lipid storage disorder was suspected, but the histiocytes did not have the cytoplasmic linearity appearance of Gaucher cells and were otherwise nonspecific. Before splenic rupture, the patient’s lipoprotein profile was reported as being normal, with no past recorded triglyceride measurement exceeding 2 mmol/L. Figure 1. Pathology and genomic studies of the index patient. (a), Hematoxylin and eosin–stained section (40×) of spleen, showing expanded white pulp displacing Malpighian bodies. The pallor is due to the abundance of foamy histiocytes in the sinusoids, seen in inset (400X). (b), LightCycler (Roche Diagnostics) analysis of genomic DNA with curve C representing the patient’s APOE melting curve at codon 158, showing heterozygosity at codon 158 for 1 TGC trinucleotide (cysteine) with Tm of 56.4 °C and 1 indeterminate trinucleotide coding sequence with a melting temperature of 62.99 °C, which was outside the Cys158 acceptable range of 63.5–68.5 °C, indicating another amino acid encoded by this residue. Melting curves for normal E2/E4 (A) and E2/E3 (B) controls are shown for reference. (c), Direct sequencing of the patient’s plasmid cloned APOE alleles showing inframe deletion …