BH4 Deficiency (Tetrahydrobiopterin Deficiency) Clinical Presentation

Updated: Sep 28, 2018
  • Author: Anna V Blenda, PhD; Chief Editor: Luis O Rohena, MD, PhD, FAAP, FACMG  more...
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Most neonates with tetrahydrobiopterin (BH4) deficiencies appear healthy at birth.

In severe 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency, the incidence of prematurity and low birth weight is increased; lead-pipe or cogwheel rigidity and stiff-baby syndrome have also been reported.

Endothelial BH4 availability is essential for maintaining pulmonary vascular homeostasis, and it is a critical mediator in the pathogenesis of pulmonary hypertension. It is also a novel therapeutic target.

BH4 restores use of the flow reserve in the coronary microcirculation in subjects with hypercholesterolemia. This finding suggests that BH4 deficiency may contribute to dysfunction of the coronary microcirculatory in hypercholesterolemia.



At birth, neonates with BH4 deficiencies often appear healthy. Pigmentary dilution can be noted. Physical findings manifest as the neonate matures.

Patients may have red hair. They may have poor suckling, decreased spontaneous movements, and a floppy-baby appearance.

If the disease is not detected on newborn screening, affected children develop progressive developmental delay and neurologic impairment that manifests as psychomotor retardation, progressive neurologic deterioration, impaired muscle tone, movement disorders, convulsions, abnormal movements, hypersalivation, and swallowing difficulties. [38]



See Pathophysiology.