Very early pattern of movement disorders in sepiapterin reductase deficiency

Background: Tetrahydrobiopterin (BH 4) deficiencies comprise a group of six rare neurometabolic disorders characterized by insufficient synthesis of the monoamine neurotransmitters dopamine and serotonin due to a disturbance of BH 4 biosynthesis or recycling. Hyperphenylalaninemia (HPA) is the first diagnostic hallmark for most BH 4 deficiencies, apart from autosomal dominant guanosine triphosphate cyclohydrolase I deficiency and sepiapterin reductase deficiency. Early supplementation of neurotransmitter precursors and where appropriate, treatment of HPA results in significant improvement of motor and cognitive function. Management approaches differ across the world and therefore these guidelines have been developed aiming to harmonize and optimize patient care. Representatives of the International Working Group on Neurotransmitter related Disorders (iNTD) developed the guidelines according to the SIGN (Scottish Intercollegiate Guidelines Network) methodology by evaluating all available evidence for the diagnosis and treatment of BH 4 deficiencies. Conclusion: Although the total body of evidence in the literature was mainly rated as low or very low, these consensus guidelines will help to harmonize clinical practice and to standardize and improve care for BH 4 deficient patients.

show abstract

“…Phenylalanine was normal to high in AR-GTPCHD and high in DHPRD [51]. PCDD and SRD had normal Phe [23,51,90,91].…”

Section: Other Diagnostic Tests: L-dopa Loading Testmentioning

confidence: 99%

Consensus guideline for the diagnosis and treatment of tetrahydrobiopterin (BH4) deficiencies

Opladen

López‐Laso

Cortès‐Saladelafont

et al. 2020

Orphanet J Rare Dis

124

View full text Add to dashboard Cite

show abstract

“…Moreover, the pterins profile in CSF is similar to that in patients with defective dihydropteridine reductase. Therefore, only 62 cases of SPD have been reported to date 69‐76 . Commonly, patients exhibit motor and speech delay, axial hypotonia, dystonia, weakness, oculogyric crises and diurnal fluctuation.…”

Section: Sepiapterin Reductase and Diseasementioning

confidence: 99%

Sepiapterin reductase: Characteristics and role in diseases

Chen

Sun

et al. 2020

J Cellular Molecular Medi

View full text Add to dashboard Cite

Sepiapterin reductase, a homodimer composed of two subunits, plays an important role in the biosynthesis of tetrahydrobiopterin. Furthermore, sepiapterin reductase exhibits a wide distribution in different tissues and is associated with many diseases, including brain dysfunction, chronic pain, cardiovascular disease and cancer. With regard to drugs targeting sepiapterin reductase, many compounds have been identified and provide potential methods to treat various diseases. However, the underlying mechanism of sepiapterin reductase in many biological processes is unclear. Therefore, this article summarized the structure, distribution and function of sepiapterin reductase, as well as the relationship between sepiapterin reductase and different diseases, with the aim of finding evidence to guide further studies on the molecular mechanisms and the potential clinical value of sepiapterin reductase. In particular, the different effects induced by the depletion of sepiapterin reductase or the inhibition of the enzyme suggest that the non‐enzymatic activity of sepiapterin reductase could function in certain biological processes, which also provides a possible direction for sepiapterin reductase research.

show abstract

“…19,20 Later, the phenotype changes toward dystonia with apparent circadian rhythm. 21 In contrast to GTPCH-D, the vast majority of SR-D patients show signs of cognitive learning disabilities. 17,22 Recently, endocrinological disturbances such as hypoglycemia and growth-hormone deficiency were identified as early symptoms of dopamine depletion in SR-D. 23 Diagnosis of these disorders may be challenging as early signs may be nonspecific and mimic cerebral palsy.…”

Section: Sepiapterin Reductase Deficiency (Dyt/park-spr)mentioning

confidence: 99%

Inherited Disorders of Neurotransmitters: Classification and Practical Approaches for Diagnosis and Treatment

et al. 2018

View full text Add to dashboard Cite

Neurotransmitter deficiencies are rare neurological disorders with clinical onset during childhood. The disorders are caused by genetic defects in the enzymes involved in synthesis, degradation, or transport of neurotransmitters or by defects in the cofactor biosynthesis such as tetrahydrobiopterin (BH4). With the newly described DNAJC12 deficiency, a chaperon-associated neurotransmitter disorder, the pathophysiological spectrum has been broadened. All deficiencies result in a lack of monoamine neurotransmitters, especially dopamine and its products, with a subset leading to decreased levels of serotonin. Symptoms can occur already in the neonatal period. Classical signs are hypotonia, movement disorders, autonomous dysregulations, and impaired development. Diagnosis depends on quantitative detection of neurotransmitters in cerebrospinal fluid, since peripheral markers in blood or urine are less reliable. Treatment is based on supplementation of the missing neurotransmitter precursors or restoring deficient cofactors for endogenous enzymatic synthesis. In recent years, knowledge about this orphan group of diseases increased substantially among clinicians. However, the difficult task of integrating clinical symptoms and laboratory values still leads to a critical delay in diagnosis and therapy for patients. This review aims at enhancing the understanding of neurotransmitter disorders and should help practicing clinicians to choose useful diagnostic steps on the way to a valid diagnosis.

show abstract

Very early pattern of movement disorders in sepiapterin reductase deficiency

Cited by 20 publications

References 7 publications

Consensus guideline for the diagnosis and treatment of tetrahydrobiopterin (BH4) deficiencies

Consensus guideline for the diagnosis and treatment of tetrahydrobiopterin (BH4) deficiencies

Sepiapterin reductase: Characteristics and role in diseases

Inherited Disorders of Neurotransmitters: Classification and Practical Approaches for Diagnosis and Treatment

Contact Info

Product

Resources

About