Novel compound heterozygous variants (c.971delA/c.542C > T) in SLC1A4 causes spastic tetraplegia, thin corpus callosum, and progressive microcephaly: a case report and mutational analysis.

Spastic tetraplegia, thin corpus callosum, and progressive microcephaly (SPATCCM) are linked to SLC1A4 genetic variants since the first reported case in 2015. SLC1A4 encodes for the neutral amino acid transporter ASCT1 which is involved in the transportation of serine between astrocytes and neurons. Although most of the reported cases are of Ashkenazi Jewish ancestry, SPATCCM has also been reported in Irish, Italian, Czech, Palestinian, and Pakistani ethnicities. Herein, we report two Pakistani male siblings from a non-consanguineous marriage presented with global developmental delay associated with spastic quadriplegia, microcephaly, and infantile spasm. Since infancy, both siblings suffered from microcephaly with brain MRI demonstrating generalized atrophy of the frontal, temporal, and parietal lobes with a prominence of the subarachnoid spaces, widening of the Sylvian fissures, and enlargement of the ventricular system not compatible with the chronological age of both patients associated with thinning of the corpus callosum. Whole-exome sequencing of both affected brothers revealed novel compound heterozygous variants in the SLC1A4 gene (NM_003038) segregating from their parents. The maternal c.971delA (p.N324Tfs*29) deletion variant disturbs the transcript reading frame leading to the generation of a premature stop codon and its subsequent degradation by nonsense-mediated mRNA decay as detected through expression analysis. The paternal c.542C > T (p.S181F) missense variant was predicted deleterious via multiple in silico prediction tools as the amino acid substitution is speculated to affect the overall ASCT1 structural confirmation due to the loss of an H-bond at the core of the protein at this position which might affect its function as concluded from the simulation analysis. The presented cases expand the genetic and clinical spectrum of ASCT1 deficiency and support the importance of including SLC1A4 gene screening in infants with unexplained global neurodevelopmental delay regardless of ethnicity.

West syndrome, developmental and epileptic encephalopathy, and severe CNS disorder associated with WWOX mutations.

Mutations in the WWOX gene have been reported in a number of patients with various neurological disorders including spino-cerebellar ataxia, intellectual disability, epilepsy, and epileptic encephalopathy. We aimed to study the clinical, electrographic, and imaging features of two new cases with WWOX mutations and compare them to previously reported cases with WWOX mutations. We assessed two unrelated children from two consanguineous families who had severe neurological disorder including early-onset spastic quadriplegia, profound developmental delay, epilepsy, and West syndrome. Based on whole-exome sequencing, we identified homozygous null mutations in WWOX in both children, and further addressed the genotype-phenotype correlation. In addition, we provide a detailed review of the previously reported cases of WWOX-related neurological disorders and compare them to the children in this report. The findings in this report expand the clinical phenotype associated with WWOX mutations and confirm a well characterised severe central nervous system disorder in association with biallelic null mutations in WWOX. This syndrome consists of profound psychomotor delay, early-onset spastic quadriplegia, and refractory epilepsy including epileptic encephalopathy, acquired microcephaly, and growth restriction. This can be associated with progressive brain atrophy, suggestive of neurodegeneration. Identification of this phenotype by clinicians may help with early diagnosis and appropriate genetic counselling.

Impact of case exposures on physician behavior responses in childhood poisoning: quality and cost implications.

OBJECTIVES: When measuring physicians' competencies, there is no consensus as to what would constitute an optimum exposure in unintentional pediatric poisoning. In the absence of universal protocols and poison centers' support, the behavior responses of the physicians can vary depending on their exposure to cases. We sought to determine if there was a correlation between the case exposure and physicians' behavior choices that could affect quality and cost of care. METHODS: A cross-sectional study was conducted in 2010, and a self-reporting survey questionnaire was given to the physicians in the pediatric emergency departments and primary care centers in the city of Al Ain. The physicians' responses were plotted against (a) the number of cases the physicians have had managed in the preceding 12 months and (b) the number of years the physicians have had been in practice RESULTS: One hundred seven physicians partook in the survey. We found that the physicians who had managed more than 2 cases of childhood poisoning in the preceding year chose significantly more positive behavior responses when compared with those who had managed 2 cases or less. There was no significant difference when the responses were measured against the physicians' number of years of practice. CONCLUSIONS: Physicians' practice effectiveness may improve if they manage at least 3 cases of childhood poisoning in a year. Physicians training modules could be developed for those physicians who do not get the optimum exposure necessary in improving physicians' behaviors associated with effective quality and cost efficiency.

A 10-month-old with rotavirus gastroenteritis, seizures, anasarca and systemic inflammatory response syndrome and complete recovery.

This report describes a 10-month-old infant who presented with generalised tonic clonic seizures following 2 days of vomiting, diarrhoea and a low-grade fever. The patient was moderately dehydrated and the blood investigations were remarkable for hyponatraemia (126 mEq/l), leukocytosis (19.4 × 10(3)/l (46% lymphocytes)), thrombocytosis (637 × 10(3)/l), hypoalbuminaemia (albumin 1.9 g/dl) and elevated C reactive protein (96 mg/l). Stool was positive for white and red blood cells but the cultures for bacteria were negative. Rotavirus antigen in stool was positive. There was microscopic haematuria without proteinuria and the nasogastric aspirate was coffee ground. Generalised oedema with pleural and peritoneal effusions ensued requiring drainage, correction of fluid and electrolytes imbalance and albumin infusions. Over the next 72 h, the patient descended into shock and disseminated intravascular coagulopathy which required packed red blood cells and fresh frozen plasma transfusions. By day 12 the patient was clinically and biochemically normal.

A failing to thrive 18 month old with vitamin D deficiency rickets and Helicobacter pylori gastritis.

A 14-month-old girl presented with the recurring bouts of vomiting and diarrhoea and failure to thrive. At 7 months of age, the baby was found to be exclusively breast fed and her blood tests revealed low calcium, low phosphorous and markedly elevated alkaline phosphatase. She was started on vitamin D and calcium supplements. Five months later, she came in with lower-limb bowing, irritability, vomiting and loose stools. The laboratory studies revealed very low serum hydroxyvitamin D, and high serum dihydroxyvitamin D. Vitamin D dose was doubled. Ten weeks later, her growth velocity had fallen and she continued to have intermittent loose stools. The oesophagogastroduodenoscopy was done and the biopsies showed Helicobacter pylori gastritis and mild duodenitis. After eradication of H pylori, there was a dramatic improvement in her growth and activity and upon 6 months follow- up there was no clinical or radiologic evidence of rickets.