Urea cycle disorders (UCDs) are rare inherited metabolic conditions that impair the effectiveness of the urea cycle responsible for removing excess ammonia from the body. The estimated incidence of UCDs is 1:35 000 births, or approximately 113 new patients with UCD per year. This review summarizes neuropsychological outcomes among patients with the eight UCDs in reports published since 1980.

Asparagine synthetase (ASNS) catalyzes the synthesis of asparagine (Asn) from aspartate and glutamine. Biallelic mutations in the ASNS gene result in ASNS Deficiency (ASNSD). Children with ASNSD exhibit congenital microcephaly, epileptic‐like seizures, and continued brain atrophy, often leading to premature mortality. This report describes a 4‐year‐old male with global developmental delay and seizures with two novel mutations in the ASNS gene, c.614A > C (maternal) and c.1192dupT (paternal) encoding p.H205P and p.Y398Lfs*4 variants, respectively. We employed the novel use of immortalized lymphoblastoid cell lines (LCL) to show that the proliferation of the heterozygotic parental LCL was not severely affected by culture in Asn‐free medium, but growth of the child's cells was suppressed by about 50%. Asn production by the LCL from both the father and the child was significantly decreased relative to the mother's cells. mRNA and protein analysis of the paternal LCL cells for the Y398Lfs*4 variant revealed reductions in both. Attempts to ectopically express the truncated Y398Lfs*4 variant in either HEK293T or ASNS‐null cells resulted in little or no detectable protein. Expression and purification of the H205P variant from HEK293T cells revealed enzymatic activity similar to wild‐type ASNS. Stable expression of WT ASNS rescued the growth of ASNS‐null JRS cells in Asn‐free medium and the H205P variant was only slightly less effective. However, the Y398Lfs*4 variant appeared to be unstable in JRS cells. These results indicate that co‐expression of the H205P and Y398Lfs*4 variants leads to a significant reduction in Asn synthesis and cellular growth.

No abstract

Background Lysosomal acid lipase deficiency (LAL-D) is an autosomal recessive disorder that can present as a severe, infantile form also known as Wolman disease. We sought to determine the outcomes and clinical needs of infants diagnosed with LAL-D, treated with enzyme replacement therapy (ERT). Methods A chart review was conducted on two infantile-onset LAL-D patients to determine clinical outcomes based on laboratory results, abdominal imaging, growth and dietary records, cardiology, endocrinology, ophthalmology, hematology, and neurocognitive evaluations. Results Two patients, both diagnosed and treated before 6 months old, demonstrated clinical improvement following weekly ERT. They required dosage increases to optimize growth and symptomatology. Both received a formula low in long chain triglycerides and high in medium chain triglycerides, an intervention that allowed significant catch-up growth. Patient 1 required treatment for partial adrenal insufficiency and hypothyroidism. Both patients demonstrated reduction in liver and spleen size and varying degrees of improved liver function. Neither experienced serious adverse reactions to ERT. Conclusion ERT has led to longer and healthier survival of affected infants. It is imperative that dietary interventions and systemic clinical care become integral to the management. Continued evidence of survival and clinical improvement in this population, coupled with available mass spectrometry enzyme assay from dried blood spots, raises the question of this rare and possibly underdiagnosed disorder’s candidacy for newborn screening. Electronic supplementary material The online version of this article (10.1186/s13023-019-1129-y) contains supplementary material, which is available to authorized users.

Ironic criticism and empathic praise are forms of social communication that influence the affective states of others in a negative or positive way. In a sample of 76 typically developing children and adolescents (mean age = 11 years; 4 months; SD: 2 years; 8 months), we studied how understanding of emotional expression (facial expression of emotion) and emotive communication (affective theory of mind) was related to the ability to understand negatively valenced ironic criticism and positively valenced empathic praise. We modelled comprehension of irony and empathy in school-aged children in relation to age and understanding of emotional expression and emotive communication. As expected, children showed significantly better understanding of emotional expression than emotive communication, which requires understanding why someone might mask their inner emotions. Meditational analyses showed that emotive communication partially mediated the relation between age and understanding ironic criticism and empathic praise. These findings suggest that the development of understanding irony and empathy over the school-age years is associated with affective attributions or affective theory of mind. Statement of contribution What is already known on this subject? Theory of mind has been found to be related to the developmental understanding of social communication. Correct interpretation of facial emotional cues is also important for interpreting social communication. What does this study add? Affective components (i.e., affective theory of mind) also contribute to the development of social communication. Emotive communication, the ability to modulate one's emotional expression according to social display rules may be predictive of social communication competency.

No abstract

No abstract

No abstract