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6-Pyruvoyl-Tetrahydropterin Synthase Deficiency

PKU


Presentation

  • We investigated five patients from four different families, four of them presenting with the severe form of PTPS deficiency and one with the mild peripheral form.[ncbi.nlm.nih.gov]
  • On RFLP analysis, a nondigested single band was present in the patient; both nondigested and 30-bp- shortened digested bands were present in the mother and the sister.[dokumen.tips]
Developmental Delay
  • Severe 6-pyruvoyl-tetrahydrobiopterin synthase deficiency is a tetrahydrobiopterin deficiency disorder that presents in infancy with developmental delay, seizures, and abnormal movements associated with hyperphenylalaninemia usually detectable by neonatal[ncbi.nlm.nih.gov]
  • Abstract Severe 6-pyruvoyl-tetrahydrobiopterin synthase deficiency is a tetrahydrobiopterin deficiency disorder that presents in infancy with developmental delay, seizures, and abnormal movements associated with hyperphenylalaninemia usually detectable[wwww.unboundmedicine.com]
  • Annals of Neurology 58(1): 164-167 2005 Severe 6-pyruvoyl-tetrahydrobiopterin synthase deficiency is a tetrahydrobiopterin deficiency disorder that presents in infancy with developmental delay, seizures, and abnormal movements associated with hyperphenylalaninemia[eurekamag.com]
  • Unless diagnosed by newborn screening via high blood phenylalanine levels, patients develop neurological problems within the first year of life, including progressive developmental delay, seizures, microcephaly, and Parkinsonian dystonia.[treatable-id.org]
  • delay with autism spectrum disorder and gait instability Developmental delay-deafness syndrome, Hildebrand type Developmental malformations-deafness-dystonia syndrome Diencephalic-mesencephalic junction dysplasia Diffuse cerebral and cerebellar atrophy-intractable[se-atlas.de]
Wheelchair Bound
  • Furthermore, she was still wheelchair-bound without any dystonia after levodopa administration.[dokumen.tips]
Scissoring Gait
  • She started to walk with an unsteady scissors gait at 4 years. Her speech and intellect were thought to be normal.[dokumen.tips]
Eczema
  • Chorea, athetosis, hypersalivation, rash with eczema, and sudden death have also been reported.[en.wikipedia.org]
Behavior Disorder
  • Reducing the L-dopa dose led to severe axial hypotonia and limb dystonia, and increasing it led to florid abnormal movements and behavioral disorders.[ncbi.nlm.nih.gov]
  • disorders syndrome X-linked hereditary sensory and autonomic neuropathy with deafness X-linked intellectual disability due to GRIA3 mutations X-linked intellectual disability with isolated growth hormone deficiency X-linked intellectual disability with[se-atlas.de]
Coarse Tremor
  • Coarse tremors often occurred in the fingers and upper limbs. By the end of the day, she was immobile with double hemiplegia-like posture. At that time she had great difficulty falling asleep.[dokumen.tips]
Tonic-Clonic Seizure
  • She had a tonic-clonic seizure at 18 months. She experienced few subsequent seizures despite being untreated. At the time, her parents noticed that she crawled mostly with her arms, and her legs were often fixed in an extended posture.[dokumen.tips]

Workup

  • Biochemical Testing and Workup Evaluation of urine and dried blood spots (DBS) can measure the levels of pterin metabolites, specifically biopterin and neopterin. Pterins are byproducts of the metabolism of tetrahydrobiopterin.[rarediseases.org]
Hyperprolactinemia
  • All experienced residual symptoms of dopamine deficiency, movement and behavioral disability, and complications of l-dopa therapy, associated with fluctuating hyperprolactinemia.[ncbi.nlm.nih.gov]

Treatment

  • The treatment of PTPS deficiency is aimed at normalizing phenylalanine levels and brain neurotransmitters.[ncbi.nlm.nih.gov]
  • Management and treatment Treatment attempts to bring phenylalaninemia levels back to normal (diet with restricted phenylalanine intake or prescription of tetrahydrobiopterin) and to restore normal monoaminergic neurotransmission by administering precursors[orpha.net]

Prognosis

  • Additionally, depending on the type of mutations, prenatal damage to the fetus may multiply the clinical abnormalities and thus worsen the prognosis of the disease.[ncbi.nlm.nih.gov]
  • Patients with the peripheral form have an excellent prognosis for normal neurologic development, provided the hyperphenylalaninemia is corrected by diet or BH4 administration.[pediatricmotordisorders.org]
  • Therefore, similar disorders of neurotransmitters, such as aromatic L -amino acid decarboxylase deficiency, that are systematically associated with a poor prognosis might have better outcomes if they were treated early.[jamanetwork.com]
  • Aromatic L-amino acid decarboxylase deficiency: clinical features, treatment and prognosis. Neurology. 2004 ;62: 1058 - 1065. Google Scholar Crossref Medline ISI Fiumara AC, Brautigam C., Hyland K., et al.[doi.org]

Etiology

  • Galanopoulou, Metabolic etiologies in West syndrome, Epilepsia Open, 3, 2, (134-166), (2018). Nastassja Himmelreich, Nan Shen, Jürgen G. Okun, Christian Thiel, Georg F.[doi.org]
  • They are organised into groups, and further divided into clinical, etiological or histopathological sub-types.[orpha.net]
  • […] malformation syndrome Spondylocostal dysostosis-hypospadias-intellectual disability syndrome Spondyloepiphyseal dysplasia tarda, Kohn type Spondyloepiphyseal dysplasia, Nishimura type Sporadic Creutzfeldt-Jakob disease Sporadic adult-onset ataxia of unknown etiology[se-atlas.de]

Epidemiology

  • Hyperphenylalaninemia due to 6-pyruvoyltetrahydropterin synthase deficiency Classification (Orphanet): - Inborn errors of metabolism - Rare genetic disease - Rare neurologic disease Classification (ICD10): - Endocrine, nutritional and metabolic diseases - Epidemiological[csbg.cnb.csic.es]
  • To provide a basis for improving the understanding of the epidemiology, genotype/phenotype correlation and outcome of these diseases their impact on the quality of life of patients, and for evaluating diagnostic and therapeutic strategies a patient registry[en.wikipedia.org]
  • This aims to provide a basis for improving our understanding of the epidemiology, genotype/phenotype correlation and outcome of these diseases, their impact on the quality of life of patients, and for evaluating diagnostic and therapeutic strategies.[intd-online.org]
  • Brin and William Koller, Epidemiology and Genetics of Essential Tremor, Movement Disorders, 13, S3, (55-63), (2008). Beat Thöny, Frank Neuheiser, Lucja Kierat, Milan Blaskovics, Pamela H.[doi.org]
Sex distribution
Age distribution

Pathophysiology

  • Dihydrofolate reductase shields endothelial nitric oxide synthase involving uncoupling intetrahydrobiopterin deficiency. [3] GTP-cyclohydrolase 1 (GCH1) and tetrahydrobiopterin are important for regulation of beta-adrenergic control of heart rate. [4] Pathophysiology[thehealthscience.com]
  • For purposes of the present invention are intended by the term "Diseases as a result of a disturbed amino acid metabolism following pathophysiological states are understood: States with elevated phenylalanine or tyrosine reduced, Serotonin or dopamine[google.sr]

Prevention

  • To prevent maternal phenylketonuria (MPKU) syndrome, special attention was paid to increasing BH(4) dosages.[ncbi.nlm.nih.gov]
  • Early treatment by administration of tetrahydrobiopterin and neurotransmitter precursors helps to prevent neurological injury, so prompt diagnosis of neonates with hyperphenylalaninemia discovered by screening for phenylketonuria is necessary.[degruyter.com]
  • BH4 helps regulate eNOS activity and prevents it from dysfunction.[selfhacked.com]
  • Tetrahydrobiopterin is also an important mediator of NO synthase regulation in type 2 diabetes and hypertension, and may be a rational therapeutic target to restore endothelial function and prevent vascular disease in these patients.[doi.org]

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