Lesch-Nyhan Syndrome — NEXUS NIGHTINGALE disease dossier

01At a glance

Gene

HPRT1

Protein

Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)UniProt P00492 · 218 aa

Inheritance

X-linked recessive — HPRT1 mutations (complete deficiency)

Age of onset

Infancy (developmental delay); self-injury typically from age 2-3

Prevalence

~1 in 380,000 (commonly cited; X-linked, almost exclusively males) — UNVERIFIED exact figure this sessionMarked unverified in the registry

02What it is

Lesch-Nyhan syndrome is an X-linked disorder of purine metabolism caused by complete HPRT1 deficiency. Affected boys develop uric acid overproduction (kidney stones, gout) alongside severe neurological disability and a striking, near-universal self-injurious biting behaviour. Allopurinol controls the uric acid but not the neurology.

03What goes wrong

Loss-of-function. Deficiency of HPRT1 (hypoxanthine-guanine phosphoribosyltransferase) blocks the purine salvage pathway, causing massive de novo purine synthesis and uric acid overproduction. This leads to hyperuricemia (kidney stones, gout, tophi) plus a poorly-understood neurological syndrome: severe motor dysfunction, intellectual disability, and characteristic self-injurious behaviour (SIB).

04How NIGHTINGALE routes it

mechanism: enzyme_lof not a degradation target

Recommended modality: urate-lowering (xanthine oxidase inhibitor) + enzyme replacement (investigational)

NOT eligible. LNS is a loss-of-function enzyme deficiency — HPRT is missing, not accumulated. Degrading any residual HPRT would worsen the disease. Correct routes are enzyme replacement / gene therapy / urate-lowering (allopurinol), not protein degradation.

05Treatment today

Allopurinol

1966 (long-established; allopurinol)

Xanthine oxidase inhibitor · 136.11 Da · PubChem CID 135401907

Lowers uric acid production by inhibiting xanthine oxidase. It treats the hyperuricemia (kidney stones, gout, tophi) but does NOT improve the neurological or behavioural symptoms.

06In the pipeline

HPRT enzyme replacement / gene therapy (preclinical)
Dopamine-pathway modulators for self-injury (investigational)
S-adenosylmethionine (SAMe) / folinic acid (reported, limited evidence)

Key reference: PMID 10338013 · PubMed

07Verification

Every line below is the registry's own verification record — what was checked, against which source, and what is still open.

uniprot: P00492 = HPRT1 (Hypoxanthine-guanine phosphoribosyltransferase), 218 aa — VERIFIED via UniProt REST API (live)
gene mutation: HPRT1 deficiency (multiple mutations; complete deficiency = Lesch-Nyhan) — VERIFIED (Orphanet ORPHAcode 510 definition)
inheritance: X-linked recessive — VERIFIED (OMIM 300322; Orphanet)
orpha code: 510 = Lesch-Nyhan syndrome (Active) — VERIFIED via Orphanet API (live, 2026-07-02)
drug mw: 136.11 Da, CID 135401907, C5H4N4O — VERIFIED via PubChem REST API (live)
fda date: Allopurinol approved 1966 (long-established) — commonly cited; exact NDA not re-verified this session

Amber entries are the registry's own open items — figures it could not re-confirm in the 2026-10-04 pass. They are shown rather than hidden.

08Sources

Fact	Source	Accession	Retrieved
Gene/protein identity	UniProt	P00492 (HPRT1, Hypoxanthine-guanine phosphoribosyltransferase, 218 aa)	2026-10-04
Disease classification & definition	Orphanet	ORPHAcode 510 (Lesch-Nyhan syndrome)	2026-10-04
Inheritance & genetics	OMIM	300322 (Lesch-Nyhan Syndrome)	2026-10-04
Drug molecular weight	PubChem	CID 135401907 (allopurinol, 136.11 Da, C5H4N4O)	2026-10-04

Source record: ORPHAN-003.json — orphan registry v2.0-fresh-2026-10-04. Protocol: TJ Compassion + L.O.V.E. — every fact live-verified against UniProt / PubChem / ClinVar / OMIM / FDA / Orphanet

Fresh orphan registry entry built 2026-10-04.

Corrections carried into registry v2 (3)

VERIFIED (2026-10-04): built fresh. ORPHAcode 510 confirmed live via Orphanet API.
NOTE: prior v1 data conflated Lesch-Nyhan (HPRT1) with progeria (LMNA) inheritance in one record — the fresh entry is gene-correct (HPRT1, not LMNA).
CLARIFIED: allopurinol treats hyperuricemia only, NOT the neurological/behavioural phenotype — this distinction was absent in prior data.

09Scope and limits

This page is a research summary for teaching and scientific communication. It is not medical advice, a diagnosis, or a treatment recommendation. NEXUS NIGHTINGALE is a computational research pipeline; it is not clinically validated and none of its output has regulatory approval. Prevalence and approval figures marked unverified must be confirmed against the cited source before external use.