What is the deficiency disease of citric acid?

November 25, 2025 •

4 min read

Citric acid is not a vitamin, and a dietary deficiency disease does not exist in the traditional sense. Instead, rare genetic conditions that disrupt the body's ability to properly utilize or transport citrate, like SLC13A5 citrate transporter disorder, cause severe metabolic and neurological problems.

Quick Summary

This article explains that true citric acid deficiency is not a medical concern because the body produces it endogenously. It details the rare genetic disorder, SLC13A5, which impairs cellular citrate transport, causing seizures and developmental delays.

Key Points

Endogenous Production: The body produces its own citric acid as a key intermediate in the Krebs cycle, meaning a dietary deficiency disease does not exist.
SLC13A5 Disorder: This rare genetic condition is the closest functional equivalent to a "citric acid deficiency," as a mutated transporter prevents citrate from entering cells.
Severe Neurological Impact: SLC13A5 disorder causes neonatal seizures, developmental delays, and movement issues due to impaired cellular metabolism.
Hypocitraturia vs. Deficiency: Hypocitraturia, or low urinary citrate, is a kidney-related issue that increases kidney stone risk and is not the same as a systemic citric acid deficiency.
B Vitamins are Co-factors: Deficiencies in B vitamins (like B1) can indirectly harm the citric acid cycle by limiting coenzymes, but they are not a citric acid deficiency.
Elevated Citrate: In SLC13A5 disorder, citrate levels are often elevated in blood and CSF because the transporter is broken, preventing it from getting inside cells.

No Deficiency Disease of Dietary Citric Acid

Contrary to common nutritional deficiencies, there is no known deficiency disease caused by a lack of dietary citric acid. The reason for this is fundamental to human metabolism: citric acid is a naturally occurring compound that the body produces on its own, primarily within the citric acid cycle (also known as the Krebs cycle or TCA cycle). This metabolic pathway is central to cellular respiration, converting glucose, fatty acids, and amino acids into energy (ATP). Therefore, dietary intake of citric acid, commonly found in citrus fruits, is not required for the body to function properly. The severe health issues related to this pathway are caused by genetic defects affecting the enzymes or transporters involved, not by a lack of ingested citric acid.

Genetic Disorders Affecting Citrate Metabolism

While you cannot have a dietary citric acid deficiency, several rare genetic disorders can disrupt the citric acid cycle or the body's handling of citrate, leading to severe illness.

SLC13A5 Citrate Transporter Disorder

This is perhaps the most direct example of a 'citrate deficiency' at the cellular level. Caused by a mutation in the SLC13A5 gene, this autosomal recessive neurodevelopmental disorder impairs the function of the Na+-coupled citrate transporter (NaCT).

Common symptoms of SLC13A5 citrate transporter disorder include:

Intractable seizures: Often beginning just hours or days after birth, these seizures are resistant to medication.
Developmental delays: Significant global delays in cognitive and motor development are characteristic.
Movement disorders: Patients can experience hypotonia (low muscle tone), ataxia (poor coordination), and dystonia (involuntary muscle contractions).
Dental abnormalities: Enamel hypoplasia, which is the poor formation of tooth enamel, is a common feature.
Elevated citrate levels: Ironically, blood and cerebrospinal fluid levels of citrate are often elevated due to the transport issue, rather than being low.

Pyruvate Carboxylase (PC) Deficiency

This inherited metabolic disorder also affects the citric acid cycle, limiting the production of oxaloacetate, a precursor for citrate. This malfunction starves the body's cells of energy, especially the brain. The symptoms vary in severity and can include lethargy, poor feeding, vomiting, seizures, developmental delay, and severe lactic acidosis.

B Vitamin Deficiencies

Deficiencies in certain B vitamins, while not a citric acid deficiency, can impair the function of the citric acid cycle. B vitamins act as essential coenzymes for various enzymes in the cycle. For example, thiamine (B1) is crucial for the pyruvate dehydrogenase and α-ketoglutarate dehydrogenase complexes. A severe thiamine deficiency, known as beriberi, can therefore lead to lactic acidosis due to impaired aerobic respiration. Similarly, pantothenic acid (B5) is required for coenzyme A, another vital component of the cycle.

Hypocitraturia: Low Urinary Citrate

This condition involves low levels of citrate in the urine and is a common risk factor for the formation of calcium-based kidney stones. Urinary citrate normally binds to calcium in the urine, preventing the formation of crystals. A low level of urinary citrate (hypocitraturia) reduces this protective effect. It can be caused by metabolic acidosis, chronic diarrhea, or a diet high in animal protein, but it is not the result of a dietary lack of citric acid. It is a localized issue related to renal handling of citrate, distinct from a systemic energy metabolism disorder.

Comparison: Dietary vs. Genetic Citrate Problems


Feature	Dietary Citric Acid Deficiency (Hypothetical)	SLC13A5 Citrate Transporter Disorder
Cause	Not possible; body produces its own citrate.	Genetic mutation in the SLC13A5 gene.
Mechanism	Not applicable.	Defective NaCT protein prevents citrate from entering cells.
Primary Problem	None.	Impaired cellular metabolism, especially in the brain, due to lack of intracellular citrate.
Symptoms	None.	Neonatal seizures, severe developmental delays, ataxia, dental issues.
Citrate Levels	Not applicable.	Elevated citrate in blood and CSF.
Diagnosis	N/A.	Genetic testing for SLC13A5 mutation.
Prognosis	N/A.	Variable, but typically involves lifelong, severe neurological dysfunction.
Treatment	N/A.	Management of symptoms, experimental therapies.

Conclusion

In summary, the notion of a "deficiency disease of citric acid" is misleading because the body produces this compound endogenously. The real health concerns related to citrate involve genetic abnormalities that disrupt the body's metabolic machinery. The SLC13A5 citrate transporter disorder is a prime example, causing severe neurological symptoms from birth due to a cellular inability to transport citrate. Other metabolic disorders and even certain vitamin deficiencies can also indirectly impact the citric acid cycle, but they are distinct from a deficiency of citric acid itself. For the vast majority of people, the levels of citric acid in the diet have no bearing on metabolic health. For more information on this rare condition, you can visit the National Organization for Rare Disorders (NORD).

Frequently Asked Questions

No, a dietary deficiency of citric acid is not possible. The human body produces citric acid endogenously as a central part of the metabolic process for energy production, so external sources from food are not necessary.

Citric acid and vitamin C (ascorbic acid) are distinct compounds. While both are found in citrus fruits, vitamin C is an essential nutrient and antioxidant, while citric acid is a non-essential acid used for flavor and preservation that the body can make on its own.

A condition called hypocitraturia, characterized by low levels of citrate in the urine, is a major risk factor for developing calcium-based kidney stones. It is caused by issues with how the kidneys handle citrate, not a dietary lack.

SLC13A5 citrate transporter disorder is a rare genetic disease caused by a mutation in the SLC13A5 gene, which prevents cells, especially brain cells, from properly transporting citrate. This leads to a severe neurological disorder with symptoms including seizures and developmental delays.

Yes, deficiencies in certain B vitamins, such as thiamine (B1) and pantothenic acid (B5), can impair the function of enzymes within the citric acid cycle. This can cause metabolic issues but is not considered a citric acid deficiency.

Diagnosis is typically confirmed through genetic testing for mutations in the SLC13A5 gene. Treatment is currently focused on managing symptoms, such as using antiseizure medications, while research into precision therapies like gene therapy is ongoing.

No, in SLC13A5 disorder, blood and cerebrospinal fluid citrate levels are typically elevated because the defective transporter prevents it from entering cells, leading to a buildup outside the cells.