[source]
pmid = PMID:30400883
title = A novel SLC6A8 mutation associated with intellectual disabilities in a Chinese family exhibiting creatine transporter deficiency: case report
[diagnosis]
disease_id = OMIM:300352
disease_label = Cerebral creatine deficiency syndrome 1
[text]
The proband was the second boy of healthy nonconsanguineous parents (pedigree in Fig. 1a). He was born at 39 weeks of
 gestation from an uneventful pregnancy and delivered by Caesarean section (weight, 3600 g; length, 50 cm; head circumference, 36 cm).
 He showed head control at 12 months, ability to sit by himself at 15 months, and walking with aid at 20 months. His verbal
 language was nearly absent and he made no visual contact. He suffered from seizures from 6 months old. He had no craniofacial
 dysmorphism. Gastrointestinal problems such as chronic constipation or nausea were noted in the proband.
 The physical examination on the proband showed 95 cm height, weight 18.2 kg and developmental and language delay.
 The proband also had an electroencephalogram (EEG) test, which showed sharp and slow waves in sleep during 24-h EEG monitoring.
 A brain stem auditory-evoked potential (BAEP) test showed mild abnormality. The proband had a Children’s Autism Rating Scale
 (CARS) score of 33, which indicated mildly autistic characteristics. The Gesell developmental scale test was used to evaluate the proband.
 Both the development age (DA) and developmental quotient (DQ) data showed extremely low grades which suggested severe development delay
 (adaptability, DA=14.23mo., DQ=23; gross motor, DA=26.37mo., DQ=43; fine movement DA=15.87mo., DQ=26; vocabulary DA=13.07mo., DQ=21;
 personal-social skill DA=13.3mo., DQ=22). The test results are depicted in Additional file 1: Figure S1A.
 The affected brother of the proband (II:1) was not available for the physical examination.
 The parental description of the clinical phenotype of the brother was mostly the same as the proband.
 The parents were physically healthy and indicated no significant past medical, surgical or family history.
Biochemical screening was performed with blood and urine samples from the proband and his mother.
The creatine/creatinine (Cr:Crn) ratio was determined by liquid chromatography-mass spectrometry with deuterated internal
standards in two urine samples taken on different days. A urine creatine test of the proband showed significantly
elevated levels of creatine (0.805 mg/ml, normal control 0.160±0.177 mg/ml) (Additional file 1: Figure S1B),
and the creatine/creatinine ratio was significantly elevated compared to controls.
Proton magnetic resonance spectroscopy (MRS, Magnetom Skyra 3.0-T, Siemens Healthcare GmbH, Erlangen, Germany),
examination using a 3.0-T system at the brain left parietal lobe, right parietal lobe and genu of corpus callosum
all showed marked reduction of the brain creatine peak (Fig. 1b left part). Brain MRI showed a thin corpus callosum
in the proband (Fig. 1b right part). The MRS and MRI examination of the mother (I:2) showed normal results (Additional file 1: Figure S1C).