Megaloblastic anemia in the context of "Azathioprine"

Lesch–Nyhan syndrome (LNS) is a rare inherited disorder caused by a deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT). This deficiency occurs due to mutations in the HPRT1 gene located on the X chromosome. LNS affects about 1 in 380,000 live births. The disorder was first recognized and clinically characterized by American medical student Michael Lesch and his mentor, pediatrician William Nyhan, at Johns Hopkins.

The HGPRT deficiency causes a build-up of uric acid in all body fluids. The combination of increased synthesis and decreased utilization of purines leads to high levels of uric acid production. This results in both high levels of uric acid in the blood and urine, associated with severe gout and kidney problems. Neurological signs include poor muscle control and moderate intellectual disability. These complications usually appear in the first year of life. Beginning in the second year of life, a particularly striking feature of LNS is self-mutilating behaviors, characterized by lip and finger biting. Neurological symptoms include facial grimacing, involuntary writhing, and repetitive movements of the arms and legs similar to those seen in Huntington's disease. The cause of the neurological abnormalities remains unknown. Because a lack of HGPRT causes the body to poorly utilize vitamin B₁₂, some males may develop megaloblastic anemia.

Folate deficiency, also known as vitamin B₉ deficiency, is a low level of folate and derivatives in the body. This may result in megaloblastic anemia in which red blood cells become abnormally large, and folate deficiency anemia is the term given for this medical condition. Signs of folate deficiency are often subtle. Symptoms may include fatigue, heart palpitations, shortness of breath, feeling faint, open sores on the tongue, loss of appetite, changes in the color of the skin or hair, irritability, and behavioral changes. Temporary reversible infertility may occur. Folate deficiency anemia during pregnancy may give rise to the birth of low weight birth premature infants and infants with neural tube defects.

Not consuming enough folate can lead to folate deficiency within a few months. Otherwise, causes may include increased needs as with pregnancy, and in those with shortened red blood cell lifespan. Folate deficiency can be secondary to vitamin B₁₂ deficiency or a defect in homocysteine methyl transferase that leads to a "folate trap" in which is an inactive metabolite that cannot be recovered. Diagnosis is typically confirmed by blood tests, including a complete blood count, and serum folate levels. Increased homocysteine levels may suggest deficiency state, but it is also affected by other factors. Vitamin B₁₂ deficiency must be ruled out, if left untreated, may cause irreversible neurological damage.