First two unrelated cases of isolated sedoheptulokinase deficiency: A benign disorder?

Abstract

We present the first two reported unrelated patients with an isolated sedoheptulokinase (SHPK) deficiency. The first patient presented with neonatal cholestasis, hypoglycemia, and anemia, while the second patient presented with congenital arthrogryposis multiplex, multiple contractures, and dysmorphisms. Both patients had elevated excretion of erythritol and sedoheptulose, and each had a homozygous nonsense mutation in SHPK. SHPK is an enzyme that phosphorylates sedoheptulose to sedoheptulose-7-phosphate, which is an important intermediate of the pentose phosphate pathway. It is questionable whether SHPK deficiency is a causal factor for the clinical phenotypes of our patients. This study illustrates the necessity of extensive functional and clinical workup for interpreting a novel variant, including nonsense variants.Electronic supplementary materialThe online version of this article (doi:10.1007/s10545-014-9809-1) contains supplementary material, which is available to authorized users.

PPP2R1B is modulated by ubiquitination and is essential for spermatogenesis

“…Results show that 7 genes ( PPP2R1B, BCKDHA, EPB41L4A, GOLGA6L10, SHPK, ST3GAL6, and UTS2R ) are expressed in testis, but none of these mouse models is correlated with fertility except Ppp2r1b ‐deficient mice designed by ourselves. To further explore the role of these 12 genes, we have done literature review, and the result shows that none of related literatures is reported on fertility 39‐49 . Thus, PPP2R1B mutation is likely correlated to non‐obstructive azoospermia.…”

“…To further explore the role of these 12 genes, we have done literature review, and the result shows that none of related literatures is reported on fertility. [39][40][41][42][43][44][45][46][47][48][49] Thus, PPP2R1B mutation is likely correlated to non-obstructive azoospermia.…”

Deficiency of the sedoheptulose kinase (Shpk) does not alter the ability of hematopoietic stem cells to rescue cystinosis in the mouse model

“…The plasticity of macrophage polarization allows them to fulfill numerous biological functions ranging from pro-inflammatory roles classified as either pro-inflammatory mediator of a type I immune response (M1 macrophages), to tissue repair, homeostasis and resolution of inflammation (M2 macrophages) [ 29 , 30 ]. In the context of our stem cell trial for cystinosis, an important function of SHPK was reported by Haschemi and colleagues on its involvement in macrophage polarization [ 20 ].…”

Elevated Erythritol: A Marker of Metabolic Dysregulation or Contributor to the Pathogenesis of Cardiometabolic Disease?

“…In transketolase deficiency, hepatic abnormalities are rare, and neither hyper- nor hypo-coagulation were reported [ 21 , 30 ]. Another genetic inborn error of PPP, sedoheptulo kinase deficiency (encoded by SHPK), is also characterized by increased endogenous erythritol synthesis [ 38 ] and increased urinary erythritol [ 38 , 39 ]. The available case report described two patients, and coagulation abnormalities were not reported [ 38 ].…”