IEMbase 0008: SPR-related sepiapterin reductase deficiency
Scope
| Field | Value |
|---|---|
| IEMbase ID | 8 |
| Nosology | 21.1.08.01 |
| Gene | SPR |
| External IDs | OMIM:182125 |
| Generated mapping | AMBIGUOUS by alias_exact:sepiapterin reductase deficiency |
| Candidate DisMech targets | Disorder_of_Catecholamine_Synthesis.yaml#Sepiapterin reductase deficiency; Tetrahydrobiopterin_Deficiency.yaml#SPR Deficiency |
| Review date | 2026-07-07 |
IEMbase phenotype signal
Characteristic clinical features are cerebral palsy-like presentation, diurnal fluctuation, hypokinesia, and psychomotor delay. Additional features include axial hypotonia, psychotic behavior, dysarthria, abnormal eye movements, gastrointestinal dysmotility, language difficulty, muscle weakness, oculogyric crisis, parkinsonism, increased tendon reflexes, and tremor.
The biochemical pattern is monoamine/BH4-related but differs from the hyperphenylalaninemic BH4 disorders: phenylalanine is listed, CSF 5-HIAA and HVA are low, phenylalanine loading is relevant, pterins include biopterin, BH2, neopterin, and sepiapterin, and prolactin is increased.
Treatments are levodopa/carbidopa, 5-hydroxytryptophan, and folinic acid.
DisMech phenotype coverage
Both local targets are meaningful. Tetrahydrobiopterin Deficiency has an SPR
Deficiency subtype and explicitly notes that hyperphenylalaninemia is typically
absent because peripheral BH4 regeneration can preserve phenylalanine handling.
It also covers dystonia, parkinsonism, oculogyric crisis, seizures,
hyperprolactinemia, pterin profiles, CSF neurotransmitter metabolites, and the
major treatments.
Disorder of Catecholamine Synthesis has a sepiapterin reductase deficiency
subtype and more directly captures the monoamine/catecholamine synthesis
context, including movement disorder, developmental delay, hypotonia,
oculogyric crisis, parkinsonism, dystonia, autonomic dysfunction, low HVA, low
5-HIAA, and carbidopa-levodopa therapy.
Concordance and completeness
Judgement: ambiguous mapping is biologically understandable rather than a simple error. For IEMbase crosswalk purposes, one canonical target should be selected to avoid double counting.
The strongest canonical target depends on the crosswalk policy. If classification
follows the BH4 pathway, use Tetrahydrobiopterin_Deficiency#SPR Deficiency. If
phenotype/mechanism follows monoamine deficiency, use
Disorder_of_Catecholamine_Synthesis#Sepiapterin reductase deficiency.
DisMech is missing several IEMbase-specific clinical details: cerebral palsy-like presentation, psychotic behavior, dysarthria, GI dysmotility, language difficulty, muscle weakness, increased tendon reflexes, tremor, and sepiapterin-specific pterin findings.
Curation actions
- Decide the canonical crosswalk target for SPR deficiency and record the other as secondary context.
- Consider explicit sepiapterin/pterin biochemical markers and diurnal fluctuation as subtype-level data.
- Review whether cerebral palsy-like presentation should be represented as a historical/misdiagnosis note rather than a core phenotype.