History

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.

Physical

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]

Causes

See Pathophysiology.

Differential Diagnoses

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Media Gallery

Autosomal recessive inheritance.

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Author

Anna V Blenda, PhD Clinical Associate Professor, Department of Biomedical Sciences, University of South Carolina School of Medicine, Greenville

Anna V Blenda, PhD is a member of the following medical societies: American Association for Cancer Research, American College of Medical Genetics and Genomics, American Society for Microbiology

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Luis O Rohena, MD, MS, FAAP, FACMG Chief, Medical Genetics, San Antonio Military Medical Center; Associate Professor of Pediatrics, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Associate Professor of Pediatrics, University of Texas Health Science Center at San Antonio

Luis O Rohena, MD, MS, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics, American Chemical Society, American College of Medical Genetics and Genomics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Additional Contributors

Erawati V Bawle, MD, FAAP, FACMG Retired Professor, Department of Pediatrics, Wayne State University School of Medicine

Erawati V Bawle, MD, FAAP, FACMG is a member of the following medical societies: American College of Medical Genetics and Genomics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Noah S Scheinfeld, JD, MD, FAAD † Assistant Clinical Professor, Department of Dermatology, Weil Cornell Medical College; Consulting Staff, Department of Dermatology, St Luke's Roosevelt Hospital Center, Beth Israel Medical Center, New York Eye and Ear Infirmary; Assistant Attending Dermatologist, New York Presbyterian Hospital; Assistant Attending Dermatologist, Lenox Hill Hospital, North Shore-LIJ Health System; Private Practice

Noah S Scheinfeld, JD, MD, FAAD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Elena L Jones, MD Clinical Assistant Professor of Dermatology, Columbia University College of Physicians and Surgeons; Clinic Chief, Department of Dermatology, St Luke's-Roosevelt Hospital Center

Disclosure: Nothing to disclose.

Sections BH4 Deficiency (Tetrahydrobiopterin Deficiency)
Overview
Presentation
- History
- Physical
- Causes
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DDx
Workup
Treatment
- Medical Care
- Consultations
- Diet
- Activity
- Prevention
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Medication
References

BH4 Deficiency (Tetrahydrobiopterin Deficiency) Clinical Presentation

History

Physical

Causes

References

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