Nutrient deficiencies are well recognized as secondary consequences of celiac disease (CD) and closely related to the clinical presentation of affected patients. Despite their clinical significance, consensus is lacking on the pattern and frequency of nutrient deficiencies in CD, the usefulness of their assessment at the time of diagnosis and during follow-up. This review aims to provide an overview of nutrient deficiencies among pediatric and adult CD patients at diagnosis and on a gluten-free diet (GFD), and their potential causes in CD. Secondly, we review their impact on CD management strategies including the potential of nutrient supplementation. A search of Medline, Pubmed and Embase until January 2019 was performed. Despite a high variability between the reported deficiencies, we noted that nutrient deficiencies occur frequently in children and adults with CD at diagnosis and during treatment with a GFD. Both inadequate dietary intake and/or diminished uptake due to intestinal dysfunction contribute to nutrient deficiencies. Most deficiencies can be restored with (long-term) treatment with a GFD and/or supplementation. However, some of them persist while others may become even more prominent during GFD. Our results indicate a lack of comprehensive evidence on the clinical efficacy of nutrient supplementation in CD management highlighting the need for further studies.

Classic galactosemia is a rare genetic metabolic disease with an unmet treatment need. Current standard of care fails to prevent chronically-debilitating brain and gonadal complications. Many mutations in the GALT gene responsible for classic galactosemia have been described to give rise to variants with conformational abnormalities. This pathogenic mechanism is highly amenable to a therapeutic strategy based on chemical/pharmacological chaperones. Arginine, a chemical chaperone, has shown beneficial effect in other inherited metabolic disorders, as well as in a prokaryotic model of classic galactosemia. The p.Q188R mutation presents a high prevalence in the Caucasian population, making it a very clinically relevant mutation. This mutation gives rise to a protein with lower conformational stability and lower catalytic activity. The aim of this study is to assess the potential therapeutic role of arginine for this mutation. Arginine aspartate administration to four patients with the p.Q188R/p.Q188R mutation, in vitro studies with three fibroblast cell lines derived from classic galactosemia patients as well as recombinant protein experiments were used to evaluate the effect of arginine in galactose metabolism. This study has been registered at https://clinicaltrials.gov (NCT03580122) on 09 July 2018. Retrospectively registered. Following a month of arginine administration, patients did not show a significant improvement of whole-body galactose oxidative capacity (p = 0.22), erythrocyte GALT activity (p = 0.87), urinary galactose (p = 0.52) and urinary galactitol levels (p = 0.41). Patients’ fibroblasts exposed to arginine did not show changes in GALT activity. Thermal shift analysis of recombinant p.Q188R GALT protein in the presence of arginine did not exhibit a positive effect. This short pilot study in four patients homozygous for the p.Q188R/p.Q188R mutation reveals that arginine has no potential therapeutic role for galactosemia patients homozygous for the p.Q188R mutation.