HVA/VMA Ratio

The HVA/VMA ratio reflects the balance between dopamine and norepinephrine/ epinephrine production by catecholamine producing neurons in the central nervous system, sympathetic nervous system, and adrenal gland.

- A common reason for an elevation of the HVA/VMA ratio is a decreased conversion of dopamine to norepinephrine. The enzyme responsible for this conversion, dopamine beta-hydroxylase (DBH), is copper and vitamin C dependent so an elevated ratio could be due to deficiencies of these cofactors .

- Another common reasons for this elevated ratio is inhibition of this enzyme by Clostridia byproducts including HPHPA, 4-cresol, or 4-hydroxyphenylacetic acid.

- Other causes of an increased ratio include inhibition of DBH by the mold metabolite fusaric acid, pharmaceuticals such as disulfiram, or food additives like aspartame.

- Another cause for an elevated ratio is a genetic variation (single nucleotide polymorphism or SNP) of the DBH enzyme. Alternatively, the activity of the DBH enzyme can be measured on blood serum.

- High ratios are common in a large number of neuropsychiatric diseases regardless of the reason for DBH deficiency.

A low HVA/VMA ratio refers to the measurement of low levels of Homovanillic Acid (HVA) and Vanillylmandelic Acid (VMA) in urine and the ratio of these two metabolites. The HVA/VMA ratio is used in medical testing, specifically for screening children for catecholamine-secreting tumors, such as neuroblastoma, pheochromocytoma, and other neural crest tumors, as well as monitoring those who have had treatment for these tumors. The test is commonly performed using a random urine specimen.

Homovanillic acid (HVA) and vanillylmandelic acid (VMA) are metabolites of the neurotransmitters dopamine and epinephrine/norepinephrine, respectively. The ratio of these metabolites can provide valuable information about certain clinical disorders and conditions.

Specifically, a low HVA/VMA ratio can indicate the following:

Dopamine Beta-Hydroxylase Deficiency: Dopamine beta-hydroxylase is an enzyme responsible for converting dopamine to norepinephrine. Inhibition of this enzyme, commonly caused by Clostridia by-products, may lead to a decreased conversion of dopamine to norepinephrine, resulting in low HVA and elevated VMA levels, and subsequently, a low HVA/VMA ratio.

It is important to note that a low HVA/VMA ratio is just one piece of information, and a comprehensive evaluation by medical professionals is necessary to interpret the test results properly. Physicians may use additional tests and clinical information to arrive at a definitive diagnosis.

The Organic Acids Test measures levels of HVA (homovanillic acid) and VMA (vanillylmandelic acid), the metabolites of the neurotransmitters, dopamine and epinephrine/norepinephrine. It also measures the ratio of the two metabolites.