Distal renal tubular acidosis with severe hypokalaemia, probably caused by colonic H(+)-K(+)-ATPase deficiency

We describe a 21 month old male infant who presented with failure to thrive associated with severe hypokalaemia and metabolic acidosis, together with hypomagnesaemia. Evaluation revealed marked renal and probable faecal potassium wasting, distal renal tubular acidosis, mild urinary magnesium wasting, and a normal gastric pH (gastric H(+)-K(+)-ATPase). Hypokalaemic forms of metabolic acidosis, such as diabetic ketoacidosis and proximal renal tubular acidosis were ruled out from the clinical picture. The hypokalaemia of distal renal tubular acidosis usually improves with alkali therapy, but this was not observed: despite correction of acidosis with 5 mmol/kg potassium citrate per day, an additional 5 mmol/kg potassium chloride was required to bring serum potassium to 3.5 mmol/l. At 3 years of age potassium was provided in the absence of potential alkali and acidosis ensued; serum bicarbonate fell to 10 mmol/l. Although a specific genetic analysis is not yet possible, the abnormalities are consistent with a novel form of distal renal tubular acidosis. The pathophysiology probably does not stem from defects in the vacuolar H(+)-ATPase but more likely from deficient activity of the colonic isoform of H(+)-K(+)-ATPase that is resident in the medullary collecting duct and mediates potassium absorption and proton secretion.     

Distal renal tubular acidosis with hereditary spherocytosis

Hereditary spherocytosis (HS) and distal renal tubular acidosis (dRTA), although distinct entities, share the same protein i.e. the anion exchanger1 (AE1) protein. Despite this, their coexistence has been rarely reported. We hereby describe the largest family to date with coexistence of dRTA and HS and discuss the molecular basis for the co-inheritance of these conditions.     

Distal renal tubular acidosis associated with celiac disease and thyroiditis

Background

Association of distal renal tubular acidosis (RTA) with autoimmune diseases is extremely rare in children.

Case Characteristics

12-year-old girl with distal RTA. Despite resolution of acidosis on bicarbonate, she continued to have poor growth and delayed puberty. Investigations revealed autoimmune thyroiditis and celiac disease.

Outcome

Levothyroxine and gluten-free diet were initiated. Child gained height and weight and had onset of puberty after gluten withdrawal.

Messages

Distal RTA in children may rarely be of autoimmune etiology.

     

Distal renal tubular acidosis in infancy: a bicarbonate wasting state.

Three unrelated infants with apparently distal RTA were investigated. Growth retardation, polyuria, nephrocalcinosis, inappropriately high urinary pH, and marked dependence of bicarbonate excretion on urinary flow were characteristic of the distal or classic form of RTA, but the urinary loss of bicarbonate at normal serum values exceeded that usually found in children or adults with this disorder. Renal tubular function was studied during hypotonic saline diuresis in the three patients and in seven healthy control infants of similar age. Fractional delivery of sodium to the distal nephron was significantly higher in the patients than in control subjects. Sodium transport at the diluting segment was not impaired. The results support the assumption that the bicarbonate wasting was the consequence of an increased delivery of this substance to an already impaired distal nephron and thus further inhibited the distal mechanisms of net acid excretion.     

The syndrome of renal tubular acidosis with nerve deafness.

Two brothers with renal tubular acidosis and nerve deafness are described. Studies of the physiopathological characteristics of the renal acidification defect show that the defect is limited to the distal tubule. Renal tubular acidosis with nerve deafness is a distinct nosologic entity that is determined by an autosomal recessive trait.     

Carbonic anhydrase II deficiency syndrome: recessive osteopetrosis with renal tubular acidosis and cerebral calcification

Four new Saudi Arabian cases of the carbonic anhydrase II deficiency syndrome from two families are described. This autosomal recessive syndrome includes osteopetrosis with renal tubular acidosis and cerebral calcification. Additional features are mental retardation, growth failure, typical facial appearance, and abnormal teeth. Two patients showed evidence of restrictive lung disease, a finding not previously described. One of the patients reported represents the first neonate reported to be affected with this syndrome. Intrauterine growth was normal, but metabolic acidosis was already evident in the neonatal period. Radiographic evidence of osteopetrosis was probably absent at birth but appeared during the late neonatal period. Carbonic anhydrase II deficiency was demonstrated in erythrocyte hemolysates from the older two siblings of this neonate, and a 50% normal level of carbonic anhydrase II was demonstrated in the erythrocyte hemolysate from their father.     

Persistent and transient distal renal tubular acidosis with bicarbonate wasting.

Bicarbonate titration studies were performed on two patients with bicarbonate wasting distal renal tubular acidosis (RTA; patients 1 and 2) and on three patients (3,4, and 5) with classic distal RTA. Daily requirements of alkali were 4.5 mEq/kg body wt in patient 1, a 3-year-old boy, and 16 mEq/kg in patient 2, a 5-month-old male infant. In contrast, only 1.5-2 mEq/kg/24 hr alkali were required in the three patients with classic distal RTA (age 8 1/2- 22 years). Patient 1 had glucose-6-phosphate dehydrogenase deficiency and patient 3 had inner ear deafness as an associated anomaly. In patient 2, the acidification defect was transient. Mean fractional excretion of bicarbonate (ChCO3-/Cin) times 100 at a plasma concentration of HCO3 below 20 mmol/liter was 5.1% in patient 1, 11.6% in patient 2, and 1.7% in patients 3-5. Minimal urine pH during the study was 7.38 in patient 1, 7.66 in patient 2, and 6.78-6.97 in the other patients. Values of net acid excretion at plasma HCO3 = 16 mmol/liter were strongly negative in patients 1 and 2 (-75 and -195 mumol/100 ml glomerular filtrate (GF), respectively) but slightly positive in the three patients with classic RTA (+3 to +20 mumol/100 ml GF). The two patients with bicarbonate wasting distal RTA were thus clearly separated from the group of patients with classic distal RTA.     

Proximal renal tubular acidosis associated with glycogen storage disease, type 9

A 2 1/2-year-old Japanese boy with glycogen storage disease, type 9, developed proximal renal tubular acidosis (RTA). The RTA significantly improved in response to cornstarch therapy, implying a direct causal relationship between subtle metabolic derangements in glycogen storage disease, type 9, and proximal RTA.     

Osteopetrosis, renal tubular acidosis without urinary concentration abnormality, cerebral calcification and severe mental retardation in three Turkish brothers.

Deficiency of carbonic anhydrase II (CA II) isoenzyme produces metabolic disorders of bone, kidney and brain. In this report we describe the clinical, radiological, pathological and genetic findings in three brothers who were affected with the autosomal recessive syndrome of osteopetrosis, renal tubular acidosis (RTA) and cerebral calcification. The RTA was hybrid type, but urinary concentration ability was intact. Additional features were severe mental retardation, stunted growth, microcephaly, dental malocclusion, high-arched palate, and broad thumbs. Previous reported patients with this syndrome were predominantly from the Middle East and Mediterranean region. This is the first report with CA II deficiency from the Turkish population. The presence of mental retardation and relative infrequency of skeletal fractures in our patients resembles the clinical course of patients with the Arabic mutation of the CA II gene, but this mutation was not found in our patients.     

SLC4A4基因变异致严重近端肾小管酸中毒伴眼部异常一例

患儿女,5岁3月龄,因肢体无力3个月余入院,生长发育落后于同龄儿、严重酸中毒,低钾血症;双眼玻璃体混浊,角膜基质灰白混浊;头颅磁共振成像示双侧基底节区可见对称性斑片状致密影。基因检测发现患儿SLC4A4基因外显子区域存在1个c.145C>T杂合变异,与其父检测结果一致;内含子区域存在一个c.1499+1G>A杂合变异,与其母检测结果一致。患儿以严重的代谢性酸中毒为特点,且伴有多系统病变,应注意先天遗传代谢性疾病,尽早行基因检测。     

Hypomagnesaemic hypocalcaemia with hypokalaemia caused by treatment with high dose gentamicin.

A 12-year-old boy developed renal wasting of magnesium, calcium, and potassium, with secondary hypomagnesaemia, hypocalcaemia, and hypokalaaemia (without hyperaldosteronism) after treatment with 14 400 mg gentamicin over 4 months. Gentamicin should not be given for prolonged courses if less toxic antibiotics are suitable. If it used, plasma magnesium, calcium, and potassium levels should be monitored during and after treatment.     

Carbonic anhydrase II deficiency: osteopetrosis, renal tubular acidosis and intracranial calcifications. Review of the literature and 3 cases

Three children in two unrelated families are affected by carbonic anhydrase II (CA II) deficiency. This disease has been reported in 27 other patients to date; the study of the pedigrees indicates that it is supported by autosomal recessive inheritance. All the patients have a very high CA I/CA II ratio (greater than 10(4) versus 6 to 10 in controls) and carrier detection is possible in obligate heterozygotes (CA I/CA II = 12 to 17). The clinical presentation consists in renal tubular acidosis, osteopetrosis and cerebral calcifications. The long term follow-up of these patients shows that the prognosis is mainly of neurological and mental expression.     

Carbonic anhydrase II deficiency: a rare autosomal recessive disorder of osteopetrosis, renal tubular acidosis, and cerebral calcification

The authors present a case of osteopetrosis due to carbonic anhydrase II deficiency. Clinical, laboratory and radiologic findings are reported. The genetics of osteopetrosis are reviewed.     

The acidification defect in the syndrome of renal tubular acidosis with nerve deafness.

An 8-year-old boy with renal tubular acidosis and nerve deafness, has been followed for seven years. Repeated studies of his renal acidification defect showed that until the age of six years the tubular defect was mixed, proximal and distal (type 1,2 hybrid). After that age the defect of proximal acidification disappeared and the patient only presented a distal renal tubular acidosis type 1. When this is associated with nerve deafness, it is considered a distinct nosological entity.