Presentation
SYNOPSIS: we present a novel mild phenotype in patients with 3-PGDH deficiency. [ncbi.nlm.nih.gov]
Entire Body System
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Feeding Difficulties
In the younger sister with the classical phenotype, feeding difficulties with recurrent gastro-oesophageal reflux prompted us to treat her temporarily with high-dose serine (1400 mg/kg/day). [ncbi.nlm.nih.gov]
In addition, the patients were irritable, hypertonic, had feeding difficulties and appeared to be “unhappy” infants. EEG recordings showed several seizure types, including hypsarithmia and multifocal epileptic activity (de Koning et al. 2002 ). [link.springer.com]
Musculoskeletal
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Hyperlaxity
In addition, he had generalised hyperlaxity of large and small joints and striae rubra on his abdomen and upper legs. His cranial MRI revealed no abnormalities. [link.springer.com]
Neurologic
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Spastic Quadriplegia
Finally, a severe spastic quadriplegia becomes evident during the first years of life. In addition, the patients were irritable, hypertonic, had feeding difficulties and appeared to be “unhappy” infants. [link.springer.com]
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Learning Difficulties
He visits a secondary school for children with learning difficulties and is actively involved in sports. At the time of diagnosis he was 16 years old and demonstrated hyperactive behaviour and mild developmental delay with an IQ of 49. [link.springer.com]
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Bilateral Ankle Clonus
His neurological exam was unremarkable except for a subtle bilateral ankle clonus. In addition, he had generalised hyperlaxity of large and small joints and striae rubra on his abdomen and upper legs. His cranial MRI revealed no abnormalities. [link.springer.com]
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Hyperactivity
At the time of diagnosis he was 16 years old and demonstrated hyperactive behaviour and mild developmental delay with an IQ of 49. His head circumference was 55 cm (10th centile) whereas his height and weight were both at the 75th centile. [link.springer.com]
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Quadriplegia
Finally, a severe spastic quadriplegia becomes evident during the first years of life. In addition, the patients were irritable, hypertonic, had feeding difficulties and appeared to be “unhappy” infants. [link.springer.com]
Workup
EEG
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Multifocal Epileptic Activity
EEG recordings showed several seizure types, including hypsarithmia and multifocal epileptic activity (de Koning et al. 2002 ). Cranial MRI scans showed a striking absence of white matter volume and hypomyelination (de Koning et al. 2000 ). [link.springer.com]
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3 Hz Spikes
At the age of nine years he presented with absence seizures (complex typical absences) and his EEG recording showed bilateral synchronous spike-wave complexes, which were enhanced after hyperventilation with typical 3 Hz spike wave complexes. [link.springer.com]
Treatment
Pre-treatment MRI demonstrated hypomyelination and profound white matter attenuation in all patients. During treatment, a significant increase in white matter volume was found and a progress of myelination in two patients. [ncbi.nlm.nih.gov]
The elder sibling was found to be normocephalic at birth and showed moderate delay of white matter myelinisation, while her seizures arrested spontaneously even without treatment. [thieme-connect.com]
Prognosis
Conclusion We have shown that a higher rate of PHGDH expression is an independent marker of prognosis in GC. [dovepress.com]
Epidemiology
Relevant External Links for PHGDH Genetic Association Database (GAD) PHGDH Human Genome Epidemiology (HuGE) Navigator PHGDH Atlas of Genetics and Cytogenetics in Oncology and Haematology: PHGDH No data available for Genatlas for PHGDH Gene Novel mutations [genecards.org]
Pathophysiology
[…] biochemistry of nutrition 180 Nutritional disorders and their management 200 Clinical biochemistry of the gastrointestinal tract 214 Assessment of hepatic function and investigation of jaundice 231 Acute and chronic liver disease 250 Glucose metabolism and the pathophysiology [books.google.de]
Molecular and Systemic Pathophysiology This enzyme defect (Fig. 1 ). causes decreased concentrations of serine and, to a lesser extent, of glycine in fasting plasma, in cerebrospinal fluid (CSF), and most probably also in brain. [link.springer.com]
Prevention
Early diagnosis in index cases allows supplementation in serine and prevention of fixed lesions. Prenatal diagnosis and genetic counseling allows prevention of secondary cases. [ncbi.nlm.nih.gov]
Disease Explained: 3-phosphoglycerate dehydrogenase deficiency is an inherited condition that prevents the body from synthesizing the amino acid serine. [nxgenmdx.com]
The lack of serine likely prevents the production of proteins and neurotransmitters in the brain and impairs the formation of normal cells and myelin. [ghr.nlm.nih.gov]
In similar case, this kind of patients should be treated preventatively with NO-Donors. On the other hand, some APOE genotypes can have a high incidence of MI. [dokumen.tips]
[…] that PHGDH inhibition is a viable mechanism for developing anticancer agents for two reasons. 36 First, a PHGDH inhibitor that cannot cross the blood–brain barrier would not interfere with serine homeostasis in the central nervous system; this would prevent [dovepress.com]