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IEMbase 0003: GCH1-related GTP cyclohydrolase I deficiency, autosomal recessive

Scope

Field Value
IEMbase ID 3
Nosology 21.1.02.01
Gene GCH1
External IDs OMIM:233910
Generated mapping UNMAPPED
Likely DisMech targets Tetrahydrobiopterin_Deficiency.yaml#GTPCH Deficiency; Disorder_of_Catecholamine_Synthesis.yaml#Autosomal recessive GTP cyclohydrolase I deficiency
Review date 2026-07-07

IEMbase phenotype signal

IEMbase presents the recessive GCH1 disorder as an early neurometabolic disease with dystonia, feeding difficulty, limb hypertonia, axial hypotonia, microcephaly, swallowing difficulty, and tremor as characteristic clinical features. Additional features include attention disorder, aggressive behavior, drooling, intellectual disability, ptosis, myoclonic seizures, and temperature instability.

The biochemical profile is BH4-deficiency-like: increased plasma phenylalanine, low CSF homovanillic acid and 5-HIAA, reduced GTPCH activity, strong BH4 loading test response, and low biopterin and neopterin in CSF, dried blood spot, and urine.

Treatments include 5-hydroxytryptophan, folinic acid, levodopa/carbidopa, phenylalanine-reduced diet, and sapropterin.

DisMech phenotype coverage

The generated crosswalk missed a real local home. Tetrahydrobiopterin Deficiency has a GTPCH Deficiency subtype with GCH1 genetics and a BH4 biosynthesis mechanism. Disorder of Catecholamine Synthesis also has an autosomal recessive GTP cyclohydrolase I deficiency subtype and covers the monoamine-deficiency axis.

At the umbrella level, DisMech covers hyperphenylalaninemia, developmental delay, intellectual disability, hypotonia, dystonia, parkinsonism, oculogyric crisis, seizures, speech delay, gait ataxia, low CSF neurotransmitter metabolites, sapropterin, levodopa/carbidopa, 5-hydroxytryptophan, folinic acid, and phenylalanine restriction.

Concordance and completeness

Judgement: mapping false negative; phenotype coverage is moderate once the manual target is selected.

DisMech captures the shared BH4/catecholamine mechanism but not the IEMbase-specific clinical pattern of swallowing difficulty, feeding difficulty, ptosis, temperature instability, tremor, and microcephaly. It also lacks a subtype-specific pterin pattern for recessive GCH1 deficiency.

Curation actions

  • Add aliases or mapper normalization so IEMbase GTPCH autosomal recessive maps to the existing local subtype.
  • Decide whether Tetrahydrobiopterin Deficiency or Disorder of Catecholamine Synthesis should be the canonical crosswalk target; the other can remain a secondary umbrella context.
  • Consider subtype-specific biochemical entries for low neopterin/biopterin and reduced GTPCH activity if evidence is available.