What are the other Names for this Condition? (Also known as/Synonyms)

• Autosomal Dominant Distal Renal Tubular Acidosis
• Autosomal Recessive Distal Renal Tubular Acidosis
• Inherited Distal Renal Tubular Acidosis

What is Familial Distal Renal Tubular Acidosis? (Definition/Background Information)

• Familial Distal Primary Acidosis, also known as Familial Distal Renal Tubular Acidosis (dRTA), is a disorder of impaired net acid secretion by the distal tubule characterized by hyperchloremic metabolic acidosis
• The classic form is often associated with hypokalemia whereas other forms of acquired dRTA may be associated with hypokalemia, hyperkalemia or normokalemia

(Source: Distal Renal Tubular Acidosis; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Who gets Familial Distal Renal Tubular Acidosis? (Age and Sex Distribution)

• Prevalence of Familial Distal Renal Tubular Acidosis is unknown but is often underreported 
• The hereditary forms of this disorder are more prevalent in areas of high consanguinity (Arabic peninsula and North Africa), whereas acquired dRTA has been reported more frequently in Western countries
• Individuals of all ages are susceptible to Familial Distal Renal Tubular Acidosis
• Autosomal recessive forms are frequently diagnosed in infants and young children
• The autosomal dominant form of the disorder is mostly diagnosed in adolescents and young adults

(Source: Distal Renal Tubular Acidosis; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

What are the Risk Factors for Familial Distal Renal Tubular Acidosis? (Predisposing Factors)

• A positive family history may be an important risk factor, since Familial Distal Renal Tubular Acidosis is inherited

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Familial Distal Renal Tubular Acidosis? (Etiology)

• Familial Distal Renal Tubular Acidosis can be caused due to mutation(s) in the following genes:
• SLC4A1 (17q21.31), causing the autosomal dominant form of the disorder
• ATP6V1B1 (2p13) orATP6V0A4gene (7q34), responsible for the autosomal recessive form with deafness
• ATP6V0A4, which causes autosomal recessive form without deafness or with late onset deafness (but overlap does exist in that some patients with this mutation develop deafness and others do not)
• Both autosomal dominant and autosomal recessive forms of inheritance are reported for Familial Distal Renal Tubular Acidosis

(Source: Distal Renal Tubular Acidosis; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Familial Distal Renal Tubular Acidosis?

Individuals with Familial Distal Renal Tubular Acidosis can be asymptomatic or can present with the following signs and symptoms:

• Polyuria
• Polydipsia
• Hypokalemia, causing weakness and fatigue
• Failure to thrive 
• Rickets 
• Urinary calcium wastage and loss of calcium salts from the bones, resulting in
• Stunting of growth in children
• Osteomalacia or osteopenia in adults 
• Hypercalciuria 
• Nephrolithiasis 
• Nephrocalcinosis 
• Low plasma potassium levels (in those with the classic form of dRTA) can lead to
• Cardiac arrhythmias
• Paralysis 
• Progressive and irreversible deafness in the recessive forms of dRTA

(Source: Distal Renal Tubular Acidosis; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

How is Familial Distal Renal Tubular Acidosis Diagnosed?

• Familial Distal Renal Tubular Acidosis is characterized by hyperchloremic metabolic acidosis. The inability to lower urine pH below 5.5 and a positive urine anion gap during spontaneous metabolic acidosis is indicative of dRTA 
• Provocative tests for further diagnosis include the NH4Cl acidifying test and the furosemide test 
• Patients with dRTA also show renal potassium wasting, except in the hyperkalemic type of dRTA 
• Molecular genetic testing for one of the causal genetic mutations can also confirm diagnosis

(Source: Distal Renal Tubular Acidosis; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Familial Distal Renal Tubular Acidosis?

The complications of Familial Distal Renal Tubular Acidosis may include:

• Weak bones
• Bone pain
• Calcium deposits in kidneys
• Chronic renal failure
• Arrhythmia 
• Paralysis

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Familial Distal Renal Tubular Acidosis Treated?

The treatment methods for Familial Distal Renal Tubular Acidosis include:

• Alkali therapy is the standard treatment (to achieve normal serum bicarbonate levels)
  • Patients are usually given sodium bicarbonate or sodium citrate 
• Children require very high doses (4-8 meq/kg/day), whereas adults need much lower doses (1-2 meq/kg/day). 
• Potassium replacement in hypokalemic patients (potassium citrate is usually recommended. The dose depends on the severity of hypokalemia) 
• Low dietary potassium intake and other therapies for hyperkalemic type of Familial Distal Renal Tubular Acidosis

(Source: Distal Renal Tubular Acidosis; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

How can Familial Distal Renal Tubular Acidosis be Prevented?

Familial Distal Renal Tubular Acidosis may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Familial Distal Renal Tubular Acidosis? (Outcomes/Resolutions)

• Familial Distal Renal Tubular Acidosis is chronic and may have significant effects on growth and development
• With treatment, there is no decrease in life expectancy and renal failure is uncommon 
• However, progressive chronic kidney disease may sometimes occur if there are recurrent kidney stones and when nephrocalcinosis is very severe

(Source: Distal Renal Tubular Acidosis; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Additional and Relevant Useful Information for Familial Distal Renal Tubular Acidosis:

Familial Distal Renal Tubular Acidosis is also known by the following names: 

• Autosomal Dominant dRTA
• Autosomal Dominant SLC4A1-Associated Distal Renal Tubular Acidosis
• Autosomal Recessive Distal Renal Tubular Acidosis with Late-Onset Sensorineural Hearing Loss
• Autosomal Recessive dRTA
• Familial Distal Primary Acidosis
• Familial dRTA
• Renal Tubular Acidosis, Autosomal Recessive with Preserved Hearing
• RTA, Classic type
• RTA, Distal type, Autosomal Dominant
• RTA, Gradient type

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/