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Hereditary Distal Renal Tubular Acidosis

Abstract
Individuals with hereditary distal renal tubular acidosis (dRTA) typically present in infancy with failure to thrive, although later presentations can occur, especially in individuals with autosomal dominant SLC4A1-dRTA. Initial clinical manifestations can also include emesis, polyuria, polydipsia, constipation, diarrhea, decreased appetite, and episodes of dehydration. Electrolyte manifestations include hyperchloremic non-anion gap metabolic acidosis and hypokalemia. Renal complications of dRTA include nephrocalcinosis, nephrolithiasis, medullary cysts, and impaired renal function. Additional manifestations include bone demineralization (rickets, osteomalacia), growth deficiency, sensorineural hearing loss (in ATP6V0A4-, ATP6V1B1-, and FOXI1-dRTA), and hereditary hemolytic anemia (in some individuals with SLC4A1-dRTA).The diagnosis of hereditary dRTA is established in a proband with dRTA and biallelic pathogenic variants in ATP6V0A4, ATP6V1B1, FOXI1, or WDR72, or a heterozygous or biallelic pathogenic variants in SLC4A1, identified by molecular genetic testing.Treatment of manifestations: Oral alkaline therapy to correct metabolic acidosis and hypokalemia with additional potassium chloride as needed; standard treatments for sensorineural hearing loss. Surveillance: Fasting venous blood gas or total CO2 prior to alkali dose in rapidly growing infants and children at least every 3-4 months, and at least every 6 months in older individuals. Serum creatinine, urea, sodium, potassium, chloride, calcium, phosphate, alkaline phosphatase, and albumin in rapidly growing infants and children at least every 3-4 months, and at least every 6 months in older individuals. Urinalysis, urine creatinine, sodium, potassium, calcium, and citrate annually and more frequently when adjusting treatment. Annual renal ultrasound to evaluate for nephrocalcinosis, urolithiasis, and cysts in asymptomatic individuals. Audiometry annually in at-risk individuals. Bone densitometry as needed. Growth assessment with calculation of body mass index in infants at least every 3 months, and in older children at least every 6 months until achievement of final height. Agents/circumstances to avoid: Potassium-sparing diuretics should be used with caution or avoided. Pregnancy management: Women with hereditary dRTA may develop severe metabolic acidosis and hypokalemia during pregnancy, especially when complicated by hyperemesis gravidarum. Close monitoring of women with hereditary dRTA during pregnancy is necessary.Hereditary dRTA caused by pathogenic variants in ATP6V0A4, ATP6V1B1, FOXI1, or WDR72 is inherited in an autosomal recessive manner. Hereditary dRTA caused by pathogenic variants in SLC4A1 is inherited in an autosomal dominant or autosomal recessive manner. Autosomal recessive inheritance: At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Autosomal dominant inheritance: Each child of an individual with autosomal dominant dRTA has a 50% chance of inheriting the pathogenic variant. Molecular genetic prenatal testing is possible for pregnancies at increased risk in families in which the pathogenic variant(s) have been identified.

Authors

No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Publisher

University of Washington, Seattle
Seattle (WA)

Language

eng

PubMed ID

31600044

Citation

Alexander RT, et al: Hereditary Distal Renal Tubular Acidosis.GeneReviews®. Edited by Adam MP, et al: University of Washington, Seattle, 1993, Seattle (WA).
Alexander RT, Law L, Gil-Peña H, et al. Hereditary Distal Renal Tubular Acidosis. Edited by Adam MP, Ardinger HH, Pagon RA, et al. GeneReviews®. Seattle (WA): University of Washington, Seattle; 1993.
Alexander RT & Law L & Gil-Peña H, et al. (1993). Hereditary Distal Renal Tubular Acidosis. Edited by Adam MP & Ardinger HH & Pagon RA, et al. In GeneReviews®. Seattle (WA): University of Washington, Seattle;
Alexander RT, et al. Edited by Adam MP, et al. GeneReviews®. Seattle (WA): University of Washington, Seattle; 1993.
* Article titles in AMA citation format should be in sentence-case
TY - CHAP T1 - Hereditary Distal Renal Tubular Acidosis BT - GeneReviews® A1 - Alexander,R Todd, AU - Law,Linda, AU - Gil-Peña,Helena, AU - Greenbaum,Larry A, AU - Santos,Fernando, Y1 - 1993/// PY - 2019/10/11/pubmed PY - 2019/10/11/medline PY - 2019/10/11/entrez KW - Classic Renal Tubular Acidosis KW - Type 1 RTA KW - Type 1 RTA KW - Classic Renal Tubular Acidosis KW - Band 3 anion transport protein KW - Forkhead box protein I1 KW - V-type proton ATPase 116 kDa subunit a isoform 4 KW - V-type proton ATPase subunit B, kidney isoform KW - WD repeat-containing protein 72 KW - ATP6V0A4 KW - ATP6V1B1 KW - FOXI1 KW - SLC4A1 KW - WDR72 KW - Hereditary Distal Renal Tubular Acidosis N2 - CLINICAL CHARACTERISTICS: Individuals with hereditary distal renal tubular acidosis (dRTA) typically present in infancy with failure to thrive, although later presentations can occur, especially in individuals with autosomal dominant SLC4A1-dRTA. Initial clinical manifestations can also include emesis, polyuria, polydipsia, constipation, diarrhea, decreased appetite, and episodes of dehydration. Electrolyte manifestations include hyperchloremic non-anion gap metabolic acidosis and hypokalemia. Renal complications of dRTA include nephrocalcinosis, nephrolithiasis, medullary cysts, and impaired renal function. Additional manifestations include bone demineralization (rickets, osteomalacia), growth deficiency, sensorineural hearing loss (in ATP6V0A4-, ATP6V1B1-, and FOXI1-dRTA), and hereditary hemolytic anemia (in some individuals with SLC4A1-dRTA). DIAGNOSIS/TESTING: The diagnosis of hereditary dRTA is established in a proband with dRTA and biallelic pathogenic variants in ATP6V0A4, ATP6V1B1, FOXI1, or WDR72, or a heterozygous or biallelic pathogenic variants in SLC4A1, identified by molecular genetic testing. MANAGEMENT: Treatment of manifestations: Oral alkaline therapy to correct metabolic acidosis and hypokalemia with additional potassium chloride as needed; standard treatments for sensorineural hearing loss. Surveillance: Fasting venous blood gas or total CO2 prior to alkali dose in rapidly growing infants and children at least every 3-4 months, and at least every 6 months in older individuals. Serum creatinine, urea, sodium, potassium, chloride, calcium, phosphate, alkaline phosphatase, and albumin in rapidly growing infants and children at least every 3-4 months, and at least every 6 months in older individuals. Urinalysis, urine creatinine, sodium, potassium, calcium, and citrate annually and more frequently when adjusting treatment. Annual renal ultrasound to evaluate for nephrocalcinosis, urolithiasis, and cysts in asymptomatic individuals. Audiometry annually in at-risk individuals. Bone densitometry as needed. Growth assessment with calculation of body mass index in infants at least every 3 months, and in older children at least every 6 months until achievement of final height. Agents/circumstances to avoid: Potassium-sparing diuretics should be used with caution or avoided. Pregnancy management: Women with hereditary dRTA may develop severe metabolic acidosis and hypokalemia during pregnancy, especially when complicated by hyperemesis gravidarum. Close monitoring of women with hereditary dRTA during pregnancy is necessary. GENETIC COUNSELING: Hereditary dRTA caused by pathogenic variants in ATP6V0A4, ATP6V1B1, FOXI1, or WDR72 is inherited in an autosomal recessive manner. Hereditary dRTA caused by pathogenic variants in SLC4A1 is inherited in an autosomal dominant or autosomal recessive manner. Autosomal recessive inheritance: At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Autosomal dominant inheritance: Each child of an individual with autosomal dominant dRTA has a 50% chance of inheriting the pathogenic variant. Molecular genetic prenatal testing is possible for pregnancies at increased risk in families in which the pathogenic variant(s) have been identified. PB - University of Washington, Seattle CY - Seattle (WA) UR - https://www.unboundmedicine.com/medline/citation/31600044/GeneReviews®:_Hereditary_Distal_Renal_Tubular_Acidosis L2 - https://www.ncbi.nlm.nih.gov/books/NBK547595 DB - PRIME DP - Unbound Medicine ER -