Allogenic hematopoietic stem cell transplantation in an Iranian patient with osteopetrosis caused by carbonic anhydrase II deficiency: A case report.

BACKGROUND: Osteopetrosis is a group of geneticall heterogeneous disorders resulting from impaired osteoclast function and bone resorption. The identification of specific genetic mutations can yield important prognostic and therapeutic implications. Herein, we present the diagnosis and successful application of hematopoietic stem cell transplantation (HSCT) in a patient with osteopetrosis caused by carbonic anhydrase II deficiency (Intermediate osteopetrosis). CASE PRESENTATION: Herein, we describe a 2.5-year-old male patient born to consanguineous parents who presented at 8-month-old with hydrocephaly, brain shunt, and developmental delay. Later at 9 months old, he was found to have eye disorder such as nystagmus, fracture of the elbow, abnormal skeletal survey, normal cell blood count (CBC), and severe hypocellularity in the bone marrow. Further evaluation showed renal tubular acidosis type 2. Whole-exome sequencing revealed a pathogenic homozygous variant in intron 2 of the carbonic anhydrase 2 gene (CA2) gene (c.232 + 1 G>T). The diagnosis of intermediate autosomal recessive osteopetrosis was established, and allogenic HSCT from his mother, a full-matched related donor (MRD), was planned. The conditioning regimen included Busulfan, Fludarabine, and Rabbit anti-thymocyte globulin. Cyclosporine and Mycophenolate Mofetil were used for graft-versus-host-disease prophylaxis. He Engrafted on day +13, and 95% chimerism was achieved. He is currently doing well without immunosuppressive therapy, now 12 months post HSCT, with normal calcium level and improving visual quality and FISH analysis revealed complete donor chimerism. DISCUSSION: HSCT could be a promising curative treatment for intermediate osteopetrosis and can provide long-term survival. Ongoing challenges in various aspects of HSCT remain to be addressed.

Young Adults With Hereditary Tubular Diseases: Practical Aspects for Adult-Focused Colleagues.

Recent advances in the management of kidney tubular diseases have resulted in a significant cohort of adolescents and young adults transitioning from pediatric- to adult-focused care. Most of the patients under adult-focused care have glomerular diseases, whereas rarer tubular diseases form a considerable proportion of pediatric patients. The purpose of this review is to highlight the clinical signs and symptoms of tubular disorders, as well as their diagnostic workup, including laboratory findings and imaging, during young adulthood. We will then discuss more common disorders such as cystinosis, cystinuria, distal kidney tubular acidosis, congenital nephrogenic diabetes insipidus, Dent disease, rickets, hypercalciuria, and syndromes such as Bartter, Fanconi, Gitelman, Liddle, and Lowe. This review is a practical guide on the diagnostic and therapeutic approach of tubular conditions affecting young adults who are transitioning to adult-focused care.

Renal Tubular Acidosis.

Renal tubular acidosis (RTA) comprises a group of disorders characterized by low capacity for net acid excretion and persistent hyperchloremic metabolic acidosis, despite preserved glomerular filtration rate. RTA are classified into chiefly three types (1, 2 and 4) based on pathophysiology and clinical and laboratory characteristics. Most patients have primary RTA that presents in infancy with polyuria, growth retardation, rickets and/or hypotonia. Diagnosis requires careful evaluation, including exclusion of other entities that can cause acidosis. A variety of tests, administered stepwise, are useful for the diagnosis and characterization of RTA. A genetic or acquired basis can be determined in majority of patients through focused evaluation. Management involves correction of acidosis and dyselectrolytemia; patients with proximal RTA with Fanconi syndrome and rickets require additional supplements of phosphate and vitamin D.

An initial evaluation of hypokalemia turned out distal renal tubular acidosis secondary to parathyroid adenoma.

Primary hyperparathyroidism (PHPT) usually presents with hypercalcemia related symptoms and signs. Kidneys play an important role in calcium homeostasis. PHPT has been reported to be associated with hyperchloremia, defective urinary acidification, and renal tubular acidosis (RTA). The dysfunction of distal renal tubules is proposed to be secondary to calcium deposition in distal tubules. This case report highlights an initial presentation of parathyroid adenoma as hypokalemia due to distal RTA secondary to medullary nephrocalcinosis.

Cerebral calcification, osteopetrosis and renal tubular acidosis: is it carbonic anhydrase-II deficiency?

Carbonic anhydrase-II deficiency is an autosomal recessive disorder with a triad of cerebral calcification, osteopetrosis and renal tubular acidosis (often combined proximal and distal). Mental retardation, growth failure, complications of osteopetrosis and other features were all recorded in this syndrome. We present a case of an Iraqi male with all these features and a positive family history.

Renal involvement in primary Sjogren syndrome of childhood: case report and literature review.

Renal tubular acidosis (RTA) is common in adults with primary Sjogren syndrome (pSS) but to date this condition has only been identified in 12 pediatric cases of pSS. Here we present the case of a 13-year-old, otherwise asymptomatic girl in whom the search for the etiology of incidentally found nephrocalcinosis led to diagnosis of distal RTA and nephrogenic diabetes insipidus secondary to SS-associated tubulointerstitial nephritis. Immunosupressive treatment and alkali/electrolyte supplementation resulted in stable renal function over the 6-year follow-up. A review of the literature focuses on two aspects of pSS: (1) the difficulties in diagnosing pSS in childhood and (2) clinical-pathological features, treatment and outcome of renal tubulointerstitial disease in childhood pSS. SS should be considered in older children, particularly females with otherwise unexplained RTA. A careful search for other renal dysfunctions is necessary, and renal biopsy may be of value in assessing the extent of renal damage and the need for immunomodulatory therapy.

Renal tubular acidosis secondary to capecitabine, oxaliplatin, and cetuximab treatment in a patient with metastatic colon carcinoma: a case report and review of the literature.

We report a case of renal tubular acidosis (RTA) secondary to capecitabine, oxaliplatin, and cetuximab administration in a 63-year-old woman with liver metastasis from colon carcinoma who had partial treatment response. On day 5 posttreatment, she arrived to the emergency room with severe weakness, and blood tests demonstrated hypokalemia with metabolic acidosis. Urine potassium levels were elevated, and the transtubular potassium gradient (TTKG) was 6.6, consistent with hypokalemic RTA with associated Fanconi syndrome, which presented as hyperphosphaturia, uricaciduria, and loss of protein and sugar in the urine. She was treated with intravenously administered potassium and fluids. RTA is one type of nephrotoxicity induced by chemotherapy, and it is reversible in mild cases when appropriately treated. The mechanism of RTA induced by chemotherapy in cancer patients has not yet been clearly elucidated. Oncologists should therefore be aware of the potential for RTA to occur after capecitabine, oxaliplatin, and cetuximab treatment, especially in the context of other predisposing factors.

Bone mineral disorder resulting from secondary distal renal tubular acidosis due to overlap syndrome (mixed connective tissue disorder) associated with coronary artery disease.

A 35 year old female presented with chronic bone mineral disorder which was due to secondary renal tubular acidosis--type 1 (RTA1). Serologically there was definite evidence of overlap syndrome (mixed connective tissue disease--M.C.T.D.), which was the cause for RTA1. During hospitalization she developed coronary artery thrombosis.

[Chronic renal failure]. / Neue Konzepte bei der chronischen Niereninsuffizienz.

The elevated cardiovascular mortality seen in patients with renal insufficiency makes it imperative that this condition be detected and treated in good time. The results of recent studies have led to fundamental changes in the therapeutic approach to the patient with kidney disease. A range of new medications is now available for the treatment of complications of renal failure.

Cleistanthus collinus poisoning.

Cleistanthus collinus is an extremely toxic plant poison. Cleistanthin A and B, the toxins of Cleistanthus collinus, are diphyllin glycosides which produce cardiac arrhythmias, urinary potassium wasting, hypoxia, metabolic acidosis and hypotension. We report ARDS, distal renal tubular acidosis and distributive shock secondary to inappropriate vasodilatation in a case following ingestion of its leaves.

Marble brain disease in two Saudi Arabian siblings.

Marble brain disease, also known as Guibaud-Vainsel syndrome, is a syndrome consisting primarily of renal tubular acidosis, cerebral calcification and osteopetrosis. The majority of reports originate from the Middle East. It is an autosomal recessive condition owing to carbonic anhydrase type II deficiency in renal and brain cells with a variant form of osteopetrosis. We report two siblings with this condition from Saudi Arabia. Both cases improved in both somatic growth and mental development after commencing treatment for renal tubular acidosis in the form of alkaline therapy and potassium supplementation.

ACP Best Practice No 181: Chemical pathology clinical investigation and management of nephrolithiasis.

Renal stones have afflicted humans for millennia but there is still no solution to this problem. This review discusses the laboratory and metabolic aspects of the clinical management of patients with renal stones, both primary and secondary in origin. First, non-pharmacological interventions such as increased fluid intake, decreased protein consumption, dietary changes in sodium, calcium, oxalate, potassium, purine, vitamins, and essential fatty acids are considered. Then specific pharmacological treatment to modify urine calcium, oxalate, urate, citrate, and acidity are considered. Finally, more unusual types of stone are examined.