Unusual diagnosis of Tangier disease during screening colonoscopy

Background Tangier disease is a rare, autosomal recessive genetic disorder associated with a deficiency in cellular cholesterol export leading to cholesterol accumulation in peripheral tissues (mainly in reticuloendothelial cells such as macrophages). While only ~100 cases have been described so far, the estimated global prevalence of 1:640.000 suggests significant underdiagnosis.

Case presentation We present the case of a 47-year-old male patient undergoing screening colonoscopy for colorectal cancer. Interestingly, colonoscopy showed a hyperpigmentation and edematous thickening of colonic mucosa in all segments. Histological evaluation revealed focal pronounced infiltration of the mucosa by CD68-positive foam cells and several polyps formed from predominantly foam cells with iron deposition.

Being clinically asymptomatic except for etiologically unexplained lymphedema with pronounced pigmentation of both lower limbs, the physical examination revealed orange-colored tonsils, laboratory findings included HDL-C levels below the detection cutoff, reduced LDL-C levels, thrombocytopenia, mildly elevated CRP levels and pronounced hyperferritinemia in the presence of reduced serum iron and normal transferrin saturation ([Table 1]). Further diagnostic examination revealed hepatosplenomegaly and mild abdominal lymphadenopathy on CT-scan. Suspecting an inherited metabolic disease, the diagnosis of Tangier disease was confirmed by genetic testing of the ABCA1 gene revealing homozygosity for a nonsense-variant in c.679C>T (Arg227*) that has so far not been described in literature.Despite an accelerated artherogenicity has been considered a hallmark of Tangier disease, coronary angiography revealed completely normal coronary arteries as well as normal carotic and lower extremity arteries.

Tab. 1

Parameter	Patient value	Reference
White blood cells (G/L)	5.2	4.4-11.3
Hemoglobin (g/dL)	13.9	14.0-17.5
MCV (fl)	97.9	80.0-96.0
MCH (pg)	32.3	27.5-33.2
Platelet count (G/L)	103	150-360
LDH (U/L)	261	125-220
Cholesterol (mg/dL)	65	0-200
HDL-C (mg/dL)	<5	>60
LDL-C (mg/dL)	31	<130
Triglycerides (mg/dL)	188	<150
CRP (mg/dL)	3.28	<0.50
Blood sedation rate (mm)	13	0-22
Iron (μg/dL)	63	65-175
Ferritin (ng/mL)	2493.3	21.8-274.7
Transferrin (mg/dL)	207	174-364
Transferrin saturation (%)	21.6	15-45

Conclusions Being considered a rare metabolic inherited disease leading to premature cardiovascular disease, we report a novel mutation associated with Tangier disease leading to a primarily gastrointestinal phenotype.

 

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Artikel online veröffentlicht:
26. August 2022