History and exam

Key diagnostic factors

common

age <12 months

Classic Lesch-Nyhan disease (LND) patients usually come to clinical attention before the age of 1 year.[26] People with an LN variant (LNV) might present at a later age, depending on the age of onset of renal problems or neurologic problems.[3]

orange "sand" crystals in diaper

Should be checked if not reported spontaneously. The "sand" is caused by uric acid crystals and microhematuria.[28][29]

kidney stones

If the hyperuricemia and hyperuricosuria is not controlled, there may be a history of nephrolithiasis.[3][26]

pyramidal signs

Spasticity and hyperreflexia, implying the involvement of corticospinal pathways, may be present.[3] Usually appears later in the course of the disease, and is often asymmetrical. The cause is unknown, but may be a result of myelopathy resulting from forceful involuntary movements of the neck.[3]

testicular atrophy

Commonly seen, and puberty is often delayed or absent.[27] Undescended testes also occur.[27][28][30]

male sex

Virtually all patients are male, owing to the X-linked recessive mode of inheritance. However, a few female patients have been described.[3]

developmental delay

Among the most frequent presenting symptoms in classic Lesch-Nyhan disease (LND), presenting as a failure to reach motor milestones.[26] Sometimes previously achieved motor milestones are lost.

involuntary movements

Usually among the presenting symptoms, but may develop later in the course of the disease.[3]

generalized hypotonia

A generalized hypotonia is frequently seen at presentation, usually in association with developmental delay.[26]

self-injurious behavior, usually at age <5 years

Typically, self-injurious behavior starts at around age 2 years. However, some reports suggest that self-injurious behavior may start in patients as young as age 6 months and in those up to age 20 years.[25]

self-injurious behavior focusing on the mouth and fingers

Finger and lip biting is a frequently seen form of self-injurious behavior. Subsequent partial amputations of the fingers, lips, tongue, and oral mucosa are common. Such topographic preference is rarely seen in other diseases with self-injury. [Figure caption and citation for the preceding image starts]: Examples of self-injurious behavior seen in patients with classic Lesch-Nyhan diseaseFrom the collection of H.A. Jinnah, MD, PhD; used with permission [Citation ends].com.bmj.content.model.Caption@3a34a026

cognitive disturbances

Cognitive function is usually impaired, with average intelligence quotient values of approximately 70, although normal intelligence has been described in some patients. Patients do not have global intellectual disability, but rather have impairments in specific cognitive domains involving attention and mental flexibility.

delayed growth

Somatic growth is affected more than head circumference or bone age.[27][28][29]

action dystonia

A generalized action dystonia is present, characterized by frequent extraneous movements in the face, neck, and limbs, with sustained muscle contractions. This results in twisted postures that interfere with voluntary movement.[3][26]

uncommon

positive family history

A history of Lesch-Nyhan disease (LND) in other family members might point toward the diagnosis. Although virtually all patients with LND are men, women may be carriers.

Risk factors

strong

positive family history

The absolute risk can be calculated based on the X-linked recessive mode of inheritance. Although virtually all patients with Lesch-Nyhan disease (LND) are men, women may be carriers. Men with classic LND do not usually have children due to the condition’s debilitating effects, although reproduction is possible in men with a mild phenotype caused by partial enzyme deficiency.

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