Serine synthesis disorders
(2014) p.123-131- Abstract
The serine synthesis pathway comprises three steps, and genetic defects are known in each of these: 3-phosphoglycerate dehydrogenase deficiency, phosphoserine aminotransferase deficiency and 3-phosphoserine phosphatase deficiency. The former has been reported in 24 patients. The majority of these patients have a severe infantile phenotype consisting of congenital microcephaly, intractable seizures with infantile onset and severe intellectual disability. Very recently, mutations in the phosphoglycerate dehydrogenase gene have been found in the Neu-Laxova syndrome, a severe dysmorphy syndrome with, as a rule, perinatal lethality. A mild, juvenile phenotype has been reported in siblings with intellectual disability and therapy-responsive... (More)
The serine synthesis pathway comprises three steps, and genetic defects are known in each of these: 3-phosphoglycerate dehydrogenase deficiency, phosphoserine aminotransferase deficiency and 3-phosphoserine phosphatase deficiency. The former has been reported in 24 patients. The majority of these patients have a severe infantile phenotype consisting of congenital microcephaly, intractable seizures with infantile onset and severe intellectual disability. Very recently, mutations in the phosphoglycerate dehydrogenase gene have been found in the Neu-Laxova syndrome, a severe dysmorphy syndrome with, as a rule, perinatal lethality. A mild, juvenile phenotype has been reported in siblings with intellectual disability and therapy-responsive absence seizures, and a Charcot-Marie-Tooth phenotype in a patient with a progressive, severe, axonal sensorimotor polyneuropathy besides other symptoms. Biochemical analysis shows a low CSF serine, a low to borderline fasting plasma serine and a low to normal CSF and fasting plasma glycine. The diagnosis is confirmed by finding mutations in 3-PHGDH. In patients with the severe, infantile form, the treatment is oral L-serine, supplemented with glycine in case of unsatisfactory clinical response. The other phenotypes responded well to serine only. Phosphoserine aminotransferase deficiency has been reported in only two patients (siblings). The brother presented with intractable seizures, acquired microcephaly, intellectual disability, and hypertonia. On biochemical investigation, there was a decrease of fasting plasma serine and glycine, and of CSF serine and glycine. Mutation analysis of PSAT1 showed two pathogenic mutations. He was treated with serine and glycine but died at the age of 7 months. His affected younger sister was treated from birth on, and this resulted in a normal outcome at the age of 3 years. 3-Phosphoserine phosphatase deficiency has been reported in only one patient, who had also Williams syndrome. Besides the dysmorphism of this syndrome, he showed a moderate intellectual disability. Fasting plasma serine levels were decreased to borderline low, and CSF serine levels were decreased. Glycine was normal in fasting plasma and in CSF. Two PSPH mutations were found. Oral serine treatment normalized the serine plasma and CSF levels, and was accompanied by a slight catch up of head growth.
(Less)
- author
- Jaeken, Jaak and de Koning, Tom LU
- publishing date
- 2014-10-01
- type
- Chapter in Book/Report/Conference proceeding
- publication status
- published
- subject
- host publication
- Congenital Neurotransmitter Disorders : A Clinical Approach - A Clinical Approach
- pages
- 9 pages
- publisher
- Nova Science Publishers, Inc.
- external identifiers
-
- scopus:84955637618
- ISBN
- 9781634630719
- 9781634630788
- language
- English
- LU publication?
- no
- id
- d54b2d87-47ed-43d8-945e-9552d894c72d
- date added to LUP
- 2020-02-26 10:07:14
- date last changed
- 2024-01-02 06:28:48
@inbook{d54b2d87-47ed-43d8-945e-9552d894c72d,
abstract = {{<p>The serine synthesis pathway comprises three steps, and genetic defects are known in each of these: 3-phosphoglycerate dehydrogenase deficiency, phosphoserine aminotransferase deficiency and 3-phosphoserine phosphatase deficiency. The former has been reported in 24 patients. The majority of these patients have a severe infantile phenotype consisting of congenital microcephaly, intractable seizures with infantile onset and severe intellectual disability. Very recently, mutations in the phosphoglycerate dehydrogenase gene have been found in the Neu-Laxova syndrome, a severe dysmorphy syndrome with, as a rule, perinatal lethality. A mild, juvenile phenotype has been reported in siblings with intellectual disability and therapy-responsive absence seizures, and a Charcot-Marie-Tooth phenotype in a patient with a progressive, severe, axonal sensorimotor polyneuropathy besides other symptoms. Biochemical analysis shows a low CSF serine, a low to borderline fasting plasma serine and a low to normal CSF and fasting plasma glycine. The diagnosis is confirmed by finding mutations in 3-PHGDH. In patients with the severe, infantile form, the treatment is oral L-serine, supplemented with glycine in case of unsatisfactory clinical response. The other phenotypes responded well to serine only. Phosphoserine aminotransferase deficiency has been reported in only two patients (siblings). The brother presented with intractable seizures, acquired microcephaly, intellectual disability, and hypertonia. On biochemical investigation, there was a decrease of fasting plasma serine and glycine, and of CSF serine and glycine. Mutation analysis of PSAT1 showed two pathogenic mutations. He was treated with serine and glycine but died at the age of 7 months. His affected younger sister was treated from birth on, and this resulted in a normal outcome at the age of 3 years. 3-Phosphoserine phosphatase deficiency has been reported in only one patient, who had also Williams syndrome. Besides the dysmorphism of this syndrome, he showed a moderate intellectual disability. Fasting plasma serine levels were decreased to borderline low, and CSF serine levels were decreased. Glycine was normal in fasting plasma and in CSF. Two PSPH mutations were found. Oral serine treatment normalized the serine plasma and CSF levels, and was accompanied by a slight catch up of head growth.</p>}},
author = {{Jaeken, Jaak and de Koning, Tom}},
booktitle = {{Congenital Neurotransmitter Disorders : A Clinical Approach}},
isbn = {{9781634630719}},
language = {{eng}},
month = {{10}},
pages = {{123--131}},
publisher = {{Nova Science Publishers, Inc.}},
title = {{Serine synthesis disorders}},
year = {{2014}},
}