Histidinuria Renal Tubular Defect

Last update 01 Nov 2024

Basic Info

Synonyms

HISTIDINURIA DUE TO A RENAL TUBULAR DEFECT, Histidine transport defect, Histidine transport defect (disorder)

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Introduction

A rare disorder of histidine metabolism characterized by histidinuria without histidinemia due to impaired intestinal and renal tubular absorption of histidine. Developmental delay, intellectual disability, seizures, and mild dysmorphic features have been reported in association. There have been no further descriptions in the literature since 1992.

100 Clinical Results associated with Histidinuria Renal Tubular Defect

100 Translational Medicine associated with Histidinuria Renal Tubular Defect

0 Patents (Medical) associated with Histidinuria Renal Tubular Defect

Literatures (Medical) associated with Histidinuria Renal Tubular Defect

01 Oct 2024·Biochemical and Biophysical Research Communications

Histidine-containing dipeptide deficiency links to hyperactivity and depression-like behaviors in old female mice

Article

Author: Matsubara, Kiminori ; Kumrungsee, Thanutchaporn ; Nishimura, Toshihide ; Umino, Mitsuki ; Egusa, Ai ; Yanaka, Noriyuki ; Braga, Jason D ; Komaru, Takumi ; Nagao, Tomoka

Carnosine, anserine, and homocarnosine are histidine-containing dipeptides (HCDs) abundant in the skeletal muscle and nervous system in mammals. To date, studies have extensively demonstrated effects of carnosine and anserine, the predominant muscular HCDs, on muscular functions and exercise performance. However, homocarnosine, the predominant brain HCD, is underexplored. Moreover, roles of homocarnosine and its related HCDs in the brain and behaviors remain poorly understood. Here, we investigated potential roles of endogenous brain homocarnosine and its related HCDs in behaviors by using carnosine synthase-1-deficient (Carns1^-/-) mice. We found that old Carns1^-/- mice (female 12 months old) exhibited hyperactivity- and depression-like behaviors with higher plasma corticosterone levels on light-dark transition and forced swimming tests, but had no defects in spontaneous locomotor activity, repetitive behavior, olfactory functions, and learning and memory abilities, as compared with their age-matched wild-type (WT) mice. We confirmed that homocarnosine and its related HCDs were deficient across brain areas of Carns1^-/- mice. Homocarnosine deficiency exhibited small effects on its constituent γ-aminobutyric acid (GABA) in the brain, in which GABA levels in hypothalamus and olfactory bulb were higher in Carns1^-/- mice than in WT mice. In WT mice, homocarnosine and GABA were highly present in hypothalamus, thalamus, and olfactory bulb, and their brain levels did not decrease in old mice when compared with younger mice (3 months old). Our present findings provide new insights into roles of homocarnosine and its related HCDs in behaviors and neurological disorders.

01 Jul 2023·Molecular and Cellular Endocrinology

The p.Cys1281Tyr variant in the hinge module/flap region of thyroglobulin causes intracellular transport disorder and congenital hypothyroidism

Article

Author: Sobrero, Gabriela ; Miras, Mirta B. ; Rivolta, Carina M. ; Adrover, Ezequiela ; Molina, Maricel F. ; Scheps, Karen G. ; Gomes Pio, Mauricio ; Targovnik, Hector M.

Congenital hypothyroidism (CH) due to thyroglobulin (TG) variants causes very low serum TG levels with normal or enlarged thyroid glands, depending on the severity of the defect, and with autosomal recessive inheritance. The purpose of this study was to functionally characterize p.Cys1281Tyr variant in the TG gene in order to increase our knowledge of the molecular mechanisms associated with CH. In order to find evidence that support the hypothesis that the p.Cys1281Tyr variant would affect the TG folding were performed amino acid prediction, 3D modeling and transient expression analysis in HEK293T cells. 18 of the 21″in silico" algorithms predict a deleterious effect of the p.Cys1281Tyr variant. The full-length 3D model p.Cys1281Tyr TG showed disulfide bond cleavage between the cysteines at positions 1249 and 1281 and rearrangement of the TG structure, while transient expression analysis indicated that p.Cys1281Tyr causes retention of the protein inside the cell. Consequently, these results show that this pathogenic variant makes it impossible for TG to fulfill its function in the biosynthesis process of thyroid hormones, causing CH. In conclusion, our results confirm the pathophysiological importance of misfolding of TG as a consequence of p.Cys1281Tyr variant located in the hinge module/flap region of TG.

01 May 2019·European Journal of PharmacologyQ3 · MEDICINE

Histidine and arginine modulate intestinal cell restitution via transforming growth factor-β1

Q3 · MEDICINE

Article

Author: Takagi, Tomohisa ; Osada-Oka, Mayuko ; Fujita, Tomoka ; Minamiyama, Yukiko ; Ichikawa, Hiroshi ; Takemura, Shigekazu ; Matsui, Tatsunobu

Intestinal wound healing depends on the precise balance of restitution, proliferation, and differentiation of intestinal epithelial cells (IECs). In a previous study, we revealed that IEC proliferation was suppressed under histidine deficiency. However, the role of histidine in cell restitution is poorly understood. Meanwhile, addition of arginine to basal medium enhanced IEC restitution after wounding. However, there are no reports on whether histidine or arginine deficiency influences IEC restitution. We examined the roles of histidine and arginine in IEC restitution using the rat intestinal epithelial cell-6 (IEC-6) cell line. In the present study, the cell restitution in medium lacking histidine (ΔHis) or arginine (ΔArg) was most greatly decreased among media lacking each of the 20 intravital amino acids, compared with that in medium containing all 20 intravital amino acids (Full). TGF-β₁ is a known repair factor for cell restitution. The TGF-β₁ extracellular concentration and Tgf-β₁ mRNA level were decreased in ΔHis or ΔArg. Supplementation of 10 µM histidine to ΔHis or 50 µM arginine to ΔArg recovered the decreases in both cell restitution and TGF-β₁ extracellular concentration. Phosphorylation of Smad2, a signaling molecule for the TGF-β pathway, was decreased in ΔHis or ΔArg. Additionally, the phosphorylation of mammalian target of rapamycin, p70 ribosomal protein S6 kinase and extracellular signal-regulated kinase were decreased in ΔHis or ΔArg. The present findings suggested that deletion of histidine or arginine led to a decrease in IEC restitution through a decrease in TGF-β₁. We revealed that histidine and arginine play important roles in IEC restitution.

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Histidinuria Renal Tubular Defect

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