Adenine Phosphoribosyltransferase Deficiency Due to Novel Mutation

Ceballos-Picot, Irène; Saha, Abhijeet; Arora, Nalini; Kapoor, Kamal K.; Kaur, Manpreet; Dhull, Rachita Singh; Goyal, Samridhi

doi:10.1016/j.ekir.2018.12.004

Cited by 6 publications

(4 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The physiologic serum and urine levels of adenine are low due to its salvage by adenine phosphoribosyltransferase (APRT) to adenosine monophosphate. When high levels of adenine are consumed, the enzyme is saturated and insoluble oxidized products of adenine accumulate in the kidney [ 44 ]. This leads to the formation of crystals in renal tubules with subsequent inflammation, fibrosis, and obstruction, resulting in kidney failure and SHP.…”

Section: Parathyroid Cell Proliferation In Secondary Hyperparathyrmentioning

confidence: 99%

Parathyroid Cell Proliferation in Secondary Hyperparathyroidism of Chronic Kidney Disease

Naveh-Many

Volovelsky

2020

IJMS

View full text Add to dashboard Cite

Secondary hyperparathyroidism (SHP) is a common complication of chronic kidney disease (CKD) that correlates with morbidity and mortality in uremic patients. It is characterized by high serum parathyroid hormone (PTH) levels and impaired bone and mineral metabolism. The main mechanisms underlying SHP are increased PTH biosynthesis and secretion as well as increased glandular mass. The mechanisms leading to parathyroid cell proliferation in SHP are not fully understood. Reduced expressions of the receptors for calcium and vitamin D contribute to the disinhibition of parathyroid cell proliferation. Activation of transforming growth factor-α-epidermal growth factor receptor (TGF-α-EGFR), nuclear factor kappa B (NF-kB), and cyclooxygenase 2- prostaglandin E2 (Cox2-PGE2) signaling all correlate with parathyroid cell proliferation, underlining their roles in the development of SHP. In addition, the mammalian target of rapamycin (mTOR) pathway is activated in parathyroid glands of experimental SHP rats. Inhibition of mTOR by rapamycin prevents and corrects the increased parathyroid cell proliferation of SHP. Mice with parathyroid-specific deletion of all miRNAs have a muted increase in serum PTH and fail to increase parathyroid cell proliferation when challenged by CKD, suggesting that miRNA is also necessary for the development of SHP. This review summarizes the current knowledge on the mechanisms of parathyroid cell proliferation in SHP.

show abstract

Section: Parathyroid Cell Proliferation In Secondary Hyperparathyrmentioning

confidence: 99%

Parathyroid Cell Proliferation in Secondary Hyperparathyroidism of Chronic Kidney Disease

Naveh-Many

Volovelsky

2020

IJMS

View full text Add to dashboard Cite

show abstract

“…There are reports of patients with APRT deficiency undergoing living related kidney transplantations (Supplementary Tables 1 and 2). 18–54 Therefore, clinical screening or genetic testing of relatives of potential living related kidney donors should be considered.…”

Section: Discussionmentioning

confidence: 99%

Adenine phosphoribosyl transferase (APRT) deficiency and a novel sequence variant in APRT with phenotypic diversity and a literature review

Leow,

Chong,

Tan

et al. 2023

Nephrology

View full text Add to dashboard Cite

Adenine phosphoribosyl transferase (APRT) deficiency is an autosomal recessive disorder and a rare cause of urolithiasis due to mutations in APRT (OMIM #102600). APRT deficiency results in increased urinary excretion of 2,8‐dihydroxyadenine (DHA) which can cause urolithiasis and kidney failure. However, with prompt diagnosis, patients with APRT deficiency can be treated with xanthine oxidoreductase inhibitors which decrease urinary DHA excretion and improve outcomes. We report a pair of siblings, an 11‐year‐old brother and his 14‐year‐old sister with compound heterozygous variants c.270del (p.Lys91Serfs*46) and c.484_486del (p.Leu162del) in APRT with variable clinical presentation of APRT deficiency. The brother presented at 17 months of age with urolithiasis and severe acute kidney injury. His elder sister remained well and asymptomatic with normal kidney function and did not develop renal calculi. Brownish disk or sphere‐like crystals with both concentric and radial markings were reported on urine microscopy in the sister on screening. The sister's diagnosis was confirmed with further laboratory evidence of absent red cell lysate APRT activity with corresponding elevated levels of urinary DHA. In conclusion, we identified a novel mutation in the APRT gene in a pair of siblings with greater phenotypic severity in the male.

show abstract

“…Most cases of DHA accumulation in urine have been reported primarily from Japan, France, Unites states of America and Iceland. Four cases of APRT deficiency have been published from Indian subcontinent but none showed crystalline nephropathy in renal transplant recipient [4–6]. Nephrolithiasis and crystalline nephropathy are two ways in which kidneys are affected [1].…”

Section: Discussionmentioning

confidence: 99%

Rare crystalline nephropathy leading to acute graft dysfunction: a case report

2019

View full text Add to dashboard Cite

BackgroundAdenine phosphoribosyl transferase (APRT) deficiency is a rare genetic form of kidney stones and/or kidney failure characterized by intratubular precipitation of 2,8 dihydroxyadenine crystals. Early diagnosis and prompt management can completely reverse the kidney injury.Case presentation44 year old Indian male, renal transplant recipient got admitted with acute graft dysfunction. Graft biopsy showed light brown refractile intratubular crystals with surrounding giant cell reaction, consistent with APRT deficiency. Patient improved after receiving allopurinol and hydration.ConclusionAPRT forms a reversible cause of crystalline nephropathy. High index of suspicion is required for the correct diagnosis as timely diagnosis has therapeutic implications.

show abstract

Adenine Phosphoribosyltransferase Deficiency Due to Novel Mutation

Cited by 6 publications

References 7 publications

Parathyroid Cell Proliferation in Secondary Hyperparathyroidism of Chronic Kidney Disease

Parathyroid Cell Proliferation in Secondary Hyperparathyroidism of Chronic Kidney Disease

Adenine phosphoribosyl transferase (APRT) deficiency and a novel sequence variant in APRT with phenotypic diversity and a literature review

Rare crystalline nephropathy leading to acute graft dysfunction: a case report

Contact Info

Product

Resources

About