Introduction
Serine deficiency
Lethal serine deficiency phenotype (Neu-Laxova syndrome)
Infantile serine deficiency phenotype
Juvenile serine deficiency phenotype
Adult serine deficiency phenotype
Diagnosis
Treatment
Serine deficiency mimic and secondary serine deficiency
Glutamine deficiency
Diagnosis
Disorder | Clinical features | Biochemical /molecular diagnosis | Treatment | Response to treatment |
---|---|---|---|---|
Serine deficiency (3-PGDH, PSAT, PSP)
|
Lethal phenotype (Neu-Laxova)
| |||
Severe IUGR, multiple congenital abnormalities, dysmorfic features, contractures, ptyrigium, syndactyly, neural tube defects | CSF serine not reported CSF glycine not reported | not reported | not reported | |
Plasma serine not reported Plasma glycine not reported | ||||
Skin: ichthyosis, collodion-like | Molecular testing in all patients | |||
MRI: atrophy, vertriculomegaly, lissencephaly, cerebellar hypoplasia, absence vermis | ||||
Infantile phenotype
(congenital) microcephaly, IUGR, intractable seizures, severe psychomotor retardation, spastic quadriplegia, cataracts, | CSF serine 6–11 μmol/L Reference 30–75 CSF glycine 1-normal μmol/L Reference 2–10 | 500mg/kg/day L-serine 200mg/kg/day glycine | Control of seizures or significantly lowered frequency, improvement of wellbeing. Increased white matter volume. No to limited effect on psychomotor development. | |
Skin: not reported | ||||
MRI: hypomyelination and delayed myelination, cerebellar abnormalities | Plasma serine 28–64 μmol/L, reference 85–235 Plasma glycine 128 μmol/L –normal, reference 145–420 |
Antenatal or presymptomatic treatment: prevention of neurological abnormalities | ||
Control of seizures, improvement of behaviour and school performance | ||||
Urine not informative | ||||
Juvenile phenotype
Mild- moderate intellectual deficiency, absence seizures, behavioural problems | 100-150mg L-serine /kg/day | |||
CSF serine 9 μmol/L Reference 20–45 CSF glycine normal Reference 2–10 Plasma serine 58,63 μmol/L reference 60–185 Plasma glycine normal Reference 125–365 | ||||
Skin: striae rubra | ||||
MRI: no abnormalities | ||||
Adult phenotype
| 120 mg L-serine /kg/day | Improvement in ADL activities | ||
Congenital cataract Psychomotor retardation Polyneuropathy, cerebellar ataxia and nystagmus | Urine not informative | |||
CSF serine 13 μmol/L Reference 15–50 CSF glycine normal Reference 2–10 Plasma serine 33 μmol/L Reference 65–170 Plasma glycine 93 μmol/L Reference 120–445 | ||||
Skin: not reported | ||||
MRI: no abnormalities | ||||
EMG: Charcot-Marie-Tooth type 2 polyneuropathy | ||||
Glutamine deficiency
|
Neonatal phenotype
| |||
Respiratory insufficiency, hypotonia, neonatal seizures, cardiac failure, gastrointestinal symptoms | Plasma glutamine 2-6 μmol/L Reference 250–700 CSF glutamine 11–12 μmol/L reference 245–650 Urine glutamine ND-8 | not possible | ||
Skin: epidermal necrolysis | ||||
MRI: abnormal gyration, cortical and cerebellar atrophy, white matter abnormalities, germinolytic cysts | ||||
Milder phenotype
Severe psychomotor retardation, intractable seizures, spastic diplegia, | L-glutamine up to 1020 mg/kg/day | Improvement of alertness and EEG abnormalities. Partial correction of CNS glutamine deficiency | ||
Skin: necrolytic skin rash | Plasma glutamine 8–354 μmol/L reference 250–700 CSF glutamine 121 μmol/L reference 245–650 | |||
MRI: hypomyelination, cortical atrophy, thin corpus callosum | ||||
Proline disorders
| ||||
P5CS deficiency (
ALDH18A1
)
|
Infantile cutis laxa phenotype
| |||
Microcephaly, progeroid features, mental retardation, hypotonia, seizures, movement disorders, joint laxicity, (intra uterine) growth retardation, cataract, corneal abnormalities | Decrease of proline, ornithine, citrulline and arginine can be found. Most patients no biochemical abnormalities Molecular testing preferred | L-ornithine therapy unsuccessful (2 sibs), L-arginine 150mg/kg/day (1 patient) | L-arginine resulted in progression of psychomotor development, correction of biochemical abnormalities and increase of brain creatine | |
Skin: cutis laxa, wrinkly skin | ||||
MRI: hypomyelination, thin corpus callosum, cerebellar abnormalities, tortuosity of brain vessels, low creatine peak on MRS | ||||
Adult phenotype
| ||||
Spastic paraparesis, psychomotor delay, cognitive defects, cataract, cyclic vomiting | Low plasma citrulline in dominant form of spastic paraparesis, low value of the total sum of plasma citrulline, ornithine, proline and arginine in recessive form Molecular testing preferred | not reported | ||
PYCR1 deficiency
| Joint laxity, typical facial features, psychomotor retardation, osteopenia, intrauterine growth retardation, hypotonia, movement disorders. Similar symptoms as in P5CS deficiency, except for cataract and corneal abnormalities | No biochemical abnormalities Molecular testing | not reported | |
Skin: cutis laxa, wrinkly skin | ||||
MRI: thin or absent corpus callosum, white matter abnormalities | ||||
PYCR2 deficiency
| Progressive microcephaly, severe failure to thrive, profound psychomotor retardation, typical facial features, seizures, spastic tetraplegia, ataxia, movement disorders | No biochemical abnormalities Molecular testing | not reported | |
Skin: no abnormalities reported | ||||
MRI: hypomyelination, thin corpus callosum, progressive cortical atrophy, cerebellar atrophy, thin brainstem, ventriculomegaly MRS elevated lactate | ||||
Asparagine deficiency
| Progressive (congenital) microcephaly, intractable seizures, hypotonia, spastic quadriplegia, severe psychomotor retardation, hyperekplexia, diaphragmatic eventration | Inconsistent biochemical abnormalities, in some patients asparagine in plasma and CSF reported to be low Molecular testing | l-asparagine 20mg/kg/day | Worsening of seizures |
Skin: no abnormalities | ||||
MRI hypomyelination, delayed myelination, cortical and cerebellar atrophy, decreased size of pons, ventriculomegaly, simplified gyration, |