Incidental diagnosis of leukocyte adhesion deficiency type II following ABO typing

Cooper, Nina; Li, Yu-Tung; Møller, Anette Torvin; Schulz‐Weidner, Nelly; Sachs, Ulrich J.; Wagner, Florian; Hackstein, Holger; Wienzek‐Lischka, Sandra; Grüneberg, Marianne; Wild, Martin K.; Bein, Gregor; Marquardt, Thorsten

doi:10.1016/j.clim.2020.108599

Cited by 8 publications

(11 citation statements)

References 19 publications

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“…Oral l ‐fucose (Hofman International Inc., Calgary, AB) was given at an initial dose of 2 g/day (50 mg/kg/day) in a single daily dose, which was gradually increased over the 27‐month treatment period to a dose of 16 g/day (400 mg/kg/day) in two divided doses. The final dose was comparable to those reported to provide clinical and biochemical effect in other LAD II patients (Cagdas et al, 2014; Cooper et al, 2020; Hidalgo et al, 2003; Marquardt, Brune, et al, 1999).…”

Section: Methodssupporting

confidence: 81%

“…In fact, even the patient described by Marquardt, Brune, et al (1999) who had some reported neurologic improvement after fucose treatment was initiated at 15 months was still noted at 4 years to be severely intellectually disabled (Wild et al, 2002). Interestingly, however, Cooper et al, 2020 reported neurologic improvement with fucose therapy in their 22‐year‐old patient, including increased cognition and attention, improved behavior, and enhanced social interactions.…”

Section: Discussionmentioning

confidence: 96%

“…These patients do not suffer from life-threatening infections and have normal leukocyte counts and non-Bombay blood types (Dauber et al, 2014;Knapp et al, 2020). Supplementation with oral L-fucose partially overcomes the fucose transporter defect in some patients with LAD II, and in these patients it leads to normalization of leukocyte counts and resolution of recurrent infections (Cagdas et al, 2014;Cooper et al, 2020;Hidalgo et al, 2003;Marquardt, Luhn, et al, 1999). To date, no studies have examined the effects of fucose therapy in patients with the attenuated form of the disease.…”

mentioning

confidence: 99%

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Defining the mild variant of leukocyte adhesion deficiency type II (SLC35C1‐congenital disorder of glycosylation) and response to l‐fucose therapy: Insights from two new families and review of the literature

Tahata

Raymond

Quade

et al. 2022

American J of Med Genetics Pt A

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Leukocyte adhesion deficiency type II (LAD II, also known as SLC35C1‐congenital disorder of glycosylation) is an autosomal recessive disorder characterized by growth and cognitive impairment, peripheral neutrophilia, recurrent infections, and the Bombay blood phenotype. A subset of patients with a milder presentation has been described with short stature and developmental delay but minimal immune and hematologic features. Some patients with LAD II benefit from oral fucose therapy, though this has not been previously studied in patients with milder disease. In this study, we describe two new patients from separate families with the milder variant of LAD II and review the published literature on this rare disorder. We demonstrate improvement in speech and cognition, CD15 expression, and core fucosylation of serum glycoproteins after 27 months of oral fucose supplementation in one patient. These patients further support the stratification of this disorder into distinct subtypes, a classical severe and an attenuated variant, and provide preliminary evidence of benefit of fucose therapy in the latter group.

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Section: Methodssupporting

confidence: 81%

Section: Discussionmentioning

confidence: 96%

mentioning

confidence: 99%

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Defining the mild variant of leukocyte adhesion deficiency type II (SLC35C1‐congenital disorder of glycosylation) and response to l‐fucose therapy: Insights from two new families and review of the literature

Tahata

Raymond

Quade

et al. 2022

American J of Med Genetics Pt A

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“…Additionally, the Golgi GDP-fucose transporter SLC35C1 showed to be significantly decreased in qPCR studies hinting to a parallel compensatory downregulation of this transporter due to the lack of its nucleotide-activated donor sugar substrate in the cytosol. As the determination of ABO and Lewis X blood group systems depend on fucosylation, some severely affected SLC35C1-CDG patients present with the Bombay blood group phenotype (Cooper et al, 2020) due to the loss of their Sialyl Lewis X structures which are normally found on granulocytes and monocytes. Notably, this was not seen in our GFUS patient.…”

Section: Discussionmentioning

confidence: 99%

A spoonful of L‐fucose—an efficient therapy for GFUS‐CDG, a new glycosylation disorder

et al. 2021

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Congenital disorders of glycosylation are a genetically and phenotypically heterogeneous family of diseases affecting the co-and posttranslational modification of proteins. Using exome sequencing, we detected biallelic variants in GFUS (NM_003313.4) c.[632G>A]; [659C>T] (p.[Gly211Glu];[Ser220Leu]) in a patient presenting with global developmental delay, mild coarse facial features and faltering growth. GFUS encodes GDP-L-fucose synthase, the terminal enzyme in de novo synthesis of GDP-L-fucose, required for fucosylation of N-and O-glycans. We found reduced GFUS protein and decreased GDP-L-fucose levels leading to a general hypofucosylation determined in patient's glycoproteins in serum, leukocytes, thrombocytes and fibroblasts. Complementation of patient fibroblasts with wild-type GFUS cDNA restored fucosylation. Making use of the GDP-L-fucose salvage pathway, oral fucose supplementation normalized fucosylation of proteins within 4 weeks as measured in serum and leukocytes. During the follow-up of 19 months, a moderate improvement of growth was seen, as well as a clear improvement of cognitive skills as measured by the Kaufmann ABC and the Nijmegen Pediatric CDG Rating Scale. In conclusion, GFUS-CDG is a new glycosylation disorder for which oral L-fucose supplementation is promising.

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“…LADII was rst diagnosed in 1992 [15]. To date, 19 individuals bearing inactivating mutations in the SLC35C1 gene have been reported [14][15][16][17][18][19][20][21][22][23] with a predominance of point mutations.…”

Section: Introductionmentioning

confidence: 99%

Insights into fucose metabolism: SLC35C1-independent fucosylation discriminates against mannose-derived GDP-fucose

Skurska

Szulc

Maszczak‐Seneczko

et al. 2021

Preprint

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Mutations in the SLC35C1 gene, encoding the Golgi GDP-fucose transporter, cause leukocyte adhesion deficiency II (LADII). Fucosylation improvement in LADII patients treated with fucose suggests the existence of an SLC35C1-independent route of GDP-fucose transport, which still remains a mystery. Here, we developed and characterized a human cell-based model deficient in the SLC35C1 activity. The knockout cells displayed low but detectable levels of fucosylation. Strikingly, the fucosylation defect was almost completely reversed upon treatment with millimolar concentrations of fucose. Even if fucose was supplemented at nanomolar concentrations, it was still incorporated into glycans by the knockout cells. We also found that the SLC35C1-independent transport preferred the salvage pathway over the de novo pathway as a source of GDP-fucose. Our results imply that the Golgi systems of GDP-fucose transport discriminate between the substrate pools obtained from different metabolic pathways, which suggests a functional connection between nucleotide sugar transporters and nucleotide sugar synthetases.

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Incidental diagnosis of leukocyte adhesion deficiency type II following ABO typing

Cited by 8 publications

References 19 publications

Defining the mild variant of leukocyte adhesion deficiency type II (SLC35C1‐congenital disorder of glycosylation) and response to l‐fucose therapy: Insights from two new families and review of the literature

Defining the mild variant of leukocyte adhesion deficiency type II (SLC35C1‐congenital disorder of glycosylation) and response to l‐fucose therapy: Insights from two new families and review of the literature

A spoonful of L‐fucose—an efficient therapy for GFUS‐CDG, a new glycosylation disorder

Insights into fucose metabolism: SLC35C1-independent fucosylation discriminates against mannose-derived GDP-fucose

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