Dietary carbohydrate modification in Niemann-Pick Type C

Peer-reviewed / Manuscript (original) received: 18.04.2018 / Revision accepted: 07.09.2018

Case series of dietary treatment during miglustat (Zavesca^®) therapy

Introduction

Niemann-Pick Type C

Niemann-Pick Type C disease (Acronym: NPC; ICD10-CM: E75.242; OMIM: 607623) is a neurodegenerative, autosomal recessive, heritable lysosomal storage disease. In 95% of cases, the NPC1 gene is affected, and in only 5% of cases, the NPC2 gene is affected [1]. The incidence of the disease is estimated at 1 in 92,000 for NPC1 and 1 in 2,900,000 for NPC2. Taking into account forms of NPC that manifest later, the combined incidence is 1.12 per 100,000 population [2].

NPC1 is an integral membrane glycoprotein of the late endosomes . The much smaller NPC2 protein can be found within the lysosomes in dissolved form [3]. If there is a fault in either of these two proteins, intracellular transport of lipids out of the lysosomes is disrupted, leading to accumulation [1, 4]. The excessive amounts of mixed lipids (mainly cholesterol and glycosphingolipids) stored in the cells causes an intensive accumulation of lipids in the brain and other organs (lipid storage disease) [3].

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Ulrike Och and Tobias Fischer contributed equally to this paper.
¹ Endosome = a vesicle in a cell that is created through endocytosis (incorporation of particles from outside the cell through invagination of the cell membrane). Late endosomes are endosomes that are mature. They are found in the middle of the cell, unlike early endosomes, which are still located near the cell membrane.
² Lysosome = an organelle in the cell with an acidic pH value that contains digestive enzymes (proteases, lipases, nucleases) for the breakdown of substances originating from the cell itself or from foreign substances.

Abstract

Niemann-Pick Type C is a neurodegenerative disease with a lethal disease course. The only approved treatment is oral administration of miglustat (Zavesca^®), a glucose derivative that competitively inhibits the first step of glycolipid biosynthesis. The main side effect that most patients experience is diarrhea, which is attributable to the inhibition of disaccharidases in the gut — sucrase-isomaltase in particular.

In two example cases, this complication was almost completely eliminated through strict reduction of disaccharides and oligosaccharides in the daily diet. In the study, the two patients were given disaccharide-free nutrition containing glucose as the sole source of carbohydrate. For the infant, this was given as bottle feed, and the adolescent female patient received it via tube feeding.

In the long term, the selection of foods the patients eat could be based on a diet that is very low in carbohydrates, such as the modified Atkins diet, or on a diet that specifically avoids large amounts of critical carbohydrates (such as sucrose, maltose, and starch). Essentially, the extent to which disaccharides must be restricted in the diet in order to reduce gastrointestinal side effects must be decided on an individual basis for each patient.

Keywords: Niemann-Pick Type C, miglustat, disaccharides, ketogenic diet, modified Atkins diet, carbohydrate reduction

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