Autopsy case of Gaucher disease type I in a patient on enzyme replacement therapy. Comments on the dynamics of persistent storage process

Abstract

We report a female patient with Gaucher disease (GD) type I on ERT (imiglucerase) for 5 years, which led to a significant general improvement. Aged 59 years she underwent an episode of altitude sickness followed by sepsis, disseminated intravascular coagulation, and multiorgan failure. She succumbed to a cerebral haemorrhage. Autopsy revealed liver cholestatic cirrhosis and multifocal liver carcinoma with immunophenotype compatible with cholangiocarcinoma. Analysis of the storage process revealed its absence or very low levels in the majority of liver and spleen macrophages. Gaucher cells (GCs) were seen only as occasional aggregates of various sizes in these organs. GCs were seen also in the leptomeninx of the cerebellum and as infrequent perivascular clusters in both the grey and white cerebral matters. Bone marrow was heavily infiltrated with GCs, especially in the adipocyte-rich part. GCs in this location displayed varied degrees of cytoplasmic vacuolation unrelated to the lysosomal compartment, caused by droplets of triglyceride, and interpreted as due to resorption of fragments of altered white adipocytes. All these observations point to the relative efficacy of ERT in covering the standard substrate load, which should not be exceeded as it would lead to the evolution of mature GCs. The results are discussed in relation to our recently published hypothesis on GD cell pathology.

Atypical cytomorphology of Gaucher cells is frequently seen in bone marrow smears from untreated patients with Gaucher disease type 1

“…The authors found foamy or vacuolated GCs in the bone marrow which were located closely to the adipose tissue. Ultrastructural examinations of these foamy GCs revealed lipid droplets in the cytosol, separated from the lysosomal compartments [11]. Two years later, in 2011 our group reported for the first time foamy GCs in the living individual [28].…”

“…infection, ischaemia). In 2009, Hůlková et al published an autopsy case of a 59 year old woman diagnosed with GD1 which was treated with ERT [11]. The authors found foamy or vacuolated GCs in the bone marrow which were located closely to the adipose tissue.…”

“…Gaucher cell (GC) is typically a large cell of 20-100 µm diameter with small, eccentrically placed nucleus, has slightly basophilic cytoplasm with characteristic crinkles or striations described as having a 'crumpled or wrinkled tissue paper' appearance ( Figure 1A) [2,5,6]. Infiltrates of GCs can be found in organs and tissues enriched in cells of the mononuclear phagocyte system, such as spleen, liver and in particular, bone marrow [5][6][7][8][9][10][11].…”

Hypertrophic Cardiomyopathy Due to the Mitochondrial DNA Mutation m.3303C>T Diagnosed in an Adult Male

“…Standard methods were employed to examine the lysosomal system, and the activities of dehydrogenases of α-glycerophosphate, succinate, nicotineamide adenine dinucleotide (NADH) and cytochrome C oxidase (COX) as described in our in previous publications. 5,6) Histological examinations showed hypertrophy and partial disarray of cardiomyocytes with disperse interstitial fibrosis ( Figure 4). Cardiomyocytes exhibited focal accumulation of glycogen.…”

Gaucher disease: a systematic review and meta‐analysis of bone complications and their response to treatment

“…Although the severity and frequency of bone pain and bone crisis may be reduced rapidly (Pastores et al 1993;Beutler et al 1995;Charrow et al 2007), improvement of bone marrow (BM) involvement can take up to 3 years (Poll et al 2001) and may respond better to higher doses of ERT (de Fost et al 2006). A recent autopsy case report of a GD1 patient on long-term ERT comments on the persistent storage of Gaucher cells in the BM as quantified via fatfraction measurement (Hůlková et al 2009). Gaucher cells were primarily noted in adipose marrow rather than in hematopoietic marrow and were observed to have phagocytosed some of the lipid contents of the surrounding adipocyte tissue.…”