Renal tubular acidosis, osteopetrosis, and cerebral calcification: A rare syndrome caused by carbonic anhydrase II deficiency

Laway, Bashir Ahmad; Mubarik, Idrees

doi:10.4103/0971-4065.209347

Cited by 7 publications

(4 citation statements)

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“…The lack of acidification occurs due to abnormality of carbonic anhydrase II enzyme, causes defective bone resorption by osteoclasts. This leads to bones becoming radio-dense and heavy, due to unopposed bone formation [93] and the accumulation of a large quantity of divalent cations, which simulates skeletal fluorosis in radiographs.…”

Section: Dental and Skeletal Fluorosis And Ckdmfomentioning

confidence: 99%

Factors Affecting the Environmentally Induced, Chronic Kidney Disease of Unknown Aetiology in Dry Zonal Regions in Tropical Countries—Novel Findings

Wimalawansa¹,

Dissanayake

2019

Environments

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A new form of chronic tubulointerstitial kidney disease (CKD) not related to diabetes or hypertension appeared during the past four decades in several peri-equatorial and predominantly agricultural countries. Commonalities include underground stagnation of drinking water with prolonged contact with rocks, harsh climatic conditions with protracted dry seasons, and rampant poverty and malnutrition. In general, the cause is unknown, and the disease is therefore named CKD of unknown aetiology (CKDu). Since it is likely caused by a combination of factors, a better term would be CKD of multifactorial origin (CKDmfo). Middle-aged malnourished men with more than 10 years of exposure to environmental hazards are the most vulnerable. Over 30 factors have been proposed as causative, including agrochemicals and heavy metals, but none has been properly tested nor proven as causative, and unlikely to be the cause of CKDmfo/CKDu. Conditions such as, having favourable climatic patterns, adequate hydration, and less poverty and malnutrition seem to prevent the disease. With the right in vivo conditions, chemical species such as calcium, phosphate, oxalate, and fluoride form intra-renal nanomineral particles initiating the CKDmfo. This article examines the key potential chemical components causing CKDmfo together with the risk factors and vulnerabilities predisposing individuals to this disease. Research findings suggest that in addition to drinking water from stagnant sources that contain high ionic components, more than 10 years of exposure to environmental nephrotoxins and micronutrient malnutrition are needed to contract this fatal disease.

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Section: Dental and Skeletal Fluorosis And Ckdmfomentioning

confidence: 99%

Factors Affecting the Environmentally Induced, Chronic Kidney Disease of Unknown Aetiology in Dry Zonal Regions in Tropical Countries—Novel Findings

Wimalawansa¹,

Dissanayake

2019

Environments

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“…В 70% случаев транслокации вызывают нарушение остеокластогенеза на стадии функционирования остеокласта: TCIRG1, CNCL7, OSTM1, CA-II, RLEKHM1, KINDIN-3, IKBKG (NEMO), MITE и др. [6,[11][12][13][14]. При мутациях с нарушениями на этапе функционирования остеокласта в пунктатах костного мозга обнаруживают нормальное или повышенное количество функционально неактивных остеокластов.…”

Section: Practice Of Allogeneic Hematopoietic Stem Cell Transplantatiunclassified

“…После алло-ТГСК у таких пациентов происходила компенсация поражения костей, но сохранялось течение тубулярного ацидоза. У части больных на поздних сроках после трансплантации отмечено прогрессирование поражения ЦНС [13,15]. При другом редко встречаемом варианте заболевания с мутацией в гене IKBKG (NEMO) преобладают симптомы тяжелого иммунодефицита [1].…”

Section: Practice Of Allogeneic Hematopoietic Stem Cell Transplantatiunclassified

Practice of allogeneic hematopoietic stem cell transplantation for infantile autosomal recessive osteopetrosis

Буря¹,

Киргизов²,

Пристанскова³

et al. 2019

Voprosy gematologii/onkologii i immunopatologii v pediatrii

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Generalized osteopetrosis is a rare hereditary disease characterized by impairment of skeleton bones formation, bone marrow dysfunction, neurologic deficiency and blindness. The main treatment for osteopetrosis is an allogeneic hematopoietic stem cell transplantation (allo-HSCT). To review and analyze experience of Department of bone marrow transplantation of RDKB (BMT RDKB) of allo-HSCT for patients with autosomal recessive generalized osteopetrosis; to evaluate tolerability and efficacy of the conditioning regiment administered. Between 2010 to 2018 years, 7 patients (2-male, 5-female) with autosomal recessive generalized osteopetrosis underwent allo-HSCT in tDepartment of bone marrow transplantation of RDKB. Median age at the moment of HSCT was 5,5 years (1–11 years). Before the transplantation myeloablative conditioning regimen was used: treosulfan, fludarabine and melphalan for 5 patients, treosulfan, fludarabine and thiotepa for 1 patient and treosulfan with fludarabine for 1 patient. In case of unrelated allo-HSCT antithymocyte globulin was added to the conditioning regimen. Bone marrow from matched (HLA- 10/10) unrelated donor was used for 4 patients, peripheral blood stem cells from matched unrelated donor was used for 1 patient, two grafts of unrelated umbilical cord blood (HLA 8/10 and 9/10) for 1 patient and peripheral blood stem cells from matched (HLA 10/10) from related donor – for 1 patient. For “graft-versus-host” disease (GVHD) prophylaxis either cyclosporine A/tacrolimus and methotrexate/ mofetil mycophenolate was used. White blood cell recovery had been achieved for 6 from 7 patients on +13 to +22 day (median +17 day). Quick autoreconstitution of hemopoesis was observed for the recipient of umbilical cord blood who got one myeloablative drug. The following early post transplantation complications were registered: oropharyngeal mucositis up to II degree in 6 patients, neutropenic enterocolitis up to II degree in 4 patients, up to III degree in 3 patients, sepsis in 3 patients. The GVHD symptoms occurred in 2 cases: skin form of II degree in one patient and skin form of II degree and intestinal form of IV degree in another patient. One patient with neurodegenerative form of osteopetrosis died with increase of hypertensive-hydrocephalus syndrome, cerebral edema with downward cerebellar herniation. During 5-6 months after allo-HSCT the 5 successfully transplanted patients experienced poor graft function but then reduction of extramedullary hemopoesis occurred and full engraftment was achieved. Hypercalcemia was reported in 2–5 months after allo-HSCT and was treated by administration of bisphosphonates. Visual impairment persisted after allo-HSCT. After 4–6 months after transplantation axis skeleton growth occurred for all 5 successfully transplanted patients, skull deformation reduced and no new zones of nerve’s compression were observed. No patients had any developmental delays after the treatment. Allo-HSCT is an effective systemic treatment of autosomal recessive generalized osteopetrosis. However because serious neurodegenerative condition cannot be reversed by allo-HSCT, such treatment may not be recommended for patients with heavy CNS impairment. Myeloablative conditioning regimen with two alkylating agents provides allogeneic reconstitution of hemopoesis. In post transplantation period, measures for hypercalcemia control are necessary. Early diagnostic of autosomal recessive generalized osteopetrosis can help to evaluate feasibility of allo-HSCT and to start treatment on time thus provide chance for long-term rehabilitation and prevention of serious disability. The study was approved by the Independent Ethics Committee of Russian Children's Clinical Hospital.

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“…In humans, an autosomal recessive condition exists where there is a lack of CA II in all body cells, leading to the development of renal tubular acidosis. This highlights the importance of this enzyme in normal renal and bodily functions 2,4,5 . Acetazolamide is an oral CAI that reversibly binds the enzyme carbonic anhydrase and renders it ineffective 6 …”

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confidence: 99%

Severe metabolic acidosis due to acetazolamide intoxication in a dog

Johnston¹,

Leister²,

Singer³

2020

Aust Veterinary J

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Case report This case report describes the clinical signs and case management of a 1‐year‐old neutered male Siberian Husky that accidentally ingested 635 mg/kg of oral acetazolamide (a carbonic anhydrase inhibitor). The dog presented with severe tachypnoea due to the development of hyperchloraemic metabolic acidosis and associated hypokalaemia that persisted for 7 days. Clinical and biochemical changes resolved with intravenous and subsequent oral supplementation of sodium bicarbonate and potassium. Complete recovery occurred within 9 days of presentation. Conclusion To the authors' knowledge, this is the first case that reports overdosage of an oral carbonic anhydrase inhibitor in a dog and subsequent recovery with adequate supplementation and supportive care.

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Renal tubular acidosis, osteopetrosis, and cerebral calcification: A rare syndrome caused by carbonic anhydrase II deficiency

Cited by 7 publications

References 4 publications

Factors Affecting the Environmentally Induced, Chronic Kidney Disease of Unknown Aetiology in Dry Zonal Regions in Tropical Countries—Novel Findings

Factors Affecting the Environmentally Induced, Chronic Kidney Disease of Unknown Aetiology in Dry Zonal Regions in Tropical Countries—Novel Findings

Practice of allogeneic hematopoietic stem cell transplantation for infantile autosomal recessive osteopetrosis

Severe metabolic acidosis due to acetazolamide intoxication in a dog

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