Un trastorno poco frecuente del ciclo de la urea en un recién nacido: deficiencia de N-acetilglutamato sintasa / A rare urea cycle disorder in a neonate: N-acetylglutamate synthetase deficiency

Los trastornos del ciclo de la urea (TCU) son enfermedades hereditarias con un posible desenlace desfavorable por hiperamoniemia grave. Se informa de una bebé con deficiencia de N-acetilglutamato sintasa (NAGS), quien tenía succión débil e hipotonicidad. Al examinarla, se observó hepatomegalia. El hemograma, los análisis y la gasometría eran normales, y las proteínas de la fase aguda, negativas. En los análisis, no se observaron cetonas en sangre, pero sí concentraciones elevadas de amoníaco. Las pruebas metabólicas no fueron concluyentes. Se inició el tratamiento de emergencia inmediatamente y recibió el alta el día 15 después del ingreso. Se confirmó deficiencia de NAGS mediante análisis de ADN. La paciente no tiene restricciones alimentarias ni toma medicamentos, excepto N-carbamil glutamato (NCG). La deficiencia de NAGS es el único TCU que puede tratarse específica y eficazmente con NCG. La detección temprana permite iniciar un tratamiento temprano y evitar los efectos devastadores de la hiperamoniemia

Urea cycle disorders (UCD), are genetically inherited diseases that may have a poor outcome due to to profound hyperammonemia. We report the case of a baby girl diagnosed as N-acetylglutamate synthase (NAGS) deficiency.The patient was evaluated due to diminished sucking and hypotonicity. Physical examination showed hepatomegaly. Complete blood count, biochemical values and blood gas analyses were normal, acute phase reactants were negative. Further laboratory analyses showed no ketones in blood and highly elevated ammonia. Metabolic tests were inconclusive. Emergency treatment was initiated immediately and she was discharged on the 15th day of admission. NAGS deficiency was confirmed by DNA-analysis. She is now without any dietary restriction or other medication, except N-carbamylglutamate (NCG).NAGS deficiency is the only UCD which can be specifically and effectively treated by NCG. Early recognition of disease will lead to early treatment that may prohibit devastating effects of hyperammonemia

Genetic analysis and prenatal diagnosis for a Chinese pedigree affected with N-acetylglutamate synthase deficiency / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a Chinese pedigree affected with N-acetylglutamate synthase deficiency.@*METHODS@#Trio whole exome sequencing (WES) was carried out for the pedigree. Pathogenicity of the identified variant was predicted based on the latest recommendation of the American College of Medical Genetics and Genomics (ACMG). Prenatal diagnosis was provided for subsequent pregnancy through Sanger sequencing.@*RESULTS@#Trio WES showed that the proband has carried compound heterozygous c.68delG and c.796G>C variants of NAGS gene, for which the mother and father were respectively heterozygous carriers. Neither variant was reported previously. Based on the ACMG guidelines, the c.68delG variant was classified as "likely pathogenic" (PVS1+PM2), while the c.796G>C variant was classified as with "uncertain significance" (PM2+BP4). Sanger sequencing validated the above findings, and only detected the heterozygous c.796G>C variant in the amniotic fluid sample. The fetus was followed up till 6 month after birth with no obvious abnormality.@*CONCLUSION@#The compound heterozygous c.68delG and c.796G>C variants of the NAGS gene probably underlay the disorder in this pedigree, and the resulth asenabled genetic counseling and prenatal diagnosis for this pedigree.

use of recombinant nag protein in spinal cord crush injury in a rat model

Objective: To evaluate the therapeutic properties of nAG protein during the recovery following acute spinal cord injuries in the rat

Study Design: An experimental study

Place and Duration of Study: King Saud University, Riyadh, Saudi Arabia, from September 2014 to September 2015

Methodology: Eight rats were studied [4 control rats and 4 experimental rats; and hence 50% were controls and 50% were experimental]

All rats were subjected to an acute spinal cord injury using the aneurysmal clip injury model. Immediately after the injury, a single intra-dural injection of either normal saline [in the control group] or the nAG protein [in the experimental group] was done. Assessment [if both groups was done over a 6-week period with regard to weight maintenance, motor recovery scores, MRI and histopathology of the injury site

Results: Weight maintenance was seen in the experimental and not in the control rats. Starting at 3 weeks after injury, the motor recovery was significantly [p<0.05] better in the experimental group

MRI assessment at 6 weeks showed better maintenance of cord continuity and less fluid accumulation at the injury site in the nAG-treated group. Just proximal to the injury site, there was less gliosis in the experimental group compared to the control group. At the crush injury site, there was less tissue architecture distortion, less vacuole formation, and less granulation tissue formation in the experimental group

Conclusion: The local injection nAG protein enhances neuro-restoration, reduces gliosis, and reduces vacuole/ granulation tissue formation following acute spinal cord crush injury in the rat aneurysmal clip animal model