Clinical, laboratory data and outcomes of 17 Iranian citrullinemia type 1 patients: Identification of five novel ASS1 gene mutations.

Citrullinemia type 1 is an autosomal recessive metabolic disease caused by ASS1 gene mutations encoding argininosuccinic acid synthetase enzyme which is within the pathway of arginine and nitric oxide biosynthesis. Disease confirmation was done by ASS1 gene mutation analysis using next-generation sequencing, DNA Sanger sequencing. The study group was 17 citrullinemia type 1 patients from 10 unrelated families referred to Iranian National Society for Study on Inborn Errors of Metabolism's clinic between 2008 and 2020. Clinical, laboratory, and molecular data were retrospectively evaluated. Eleven different ASS1 gene mutations were detected in 13 (76%) of 17 neonatal, three (18%) of 17 late infantile, and one (6%) of 17 asymptomatic patients. Severe developmental delay and intractable seizures despite metabolic control was outcome of neonatal form survivor. Two late infantile form patients live metabolically controlled with quite normal performance. DNA mutations are as follows: seven missense, one nonsense, and two insertion/deletion mutations in 12, two, and three patients, respectively. Five novel mutations were detected including a homozygous GG deletion in exon 12 (c.790_791delGG;p.Gly264Profs*3) and a homozygous mutation in exon 7 (c.440C>T; p.Met147Thr), both causing infantile (late onset) form; a homozygous mutation in exon 6 (c.1130T>C; p.Met376Thr) causing neonatal form; two compound heterozygote mutations in exon 14 (c.1167_1168insC:p.Gly390Argfs*22& c.1186T>A; p.Ser396Thr) causing asymptomatic form. Five (38%) patients with classic neonatal form had mutation in exon 14 of ASS1 (c.1168G>A; p.Gly390Arg). Classic neonatal was the most common form of disease in Iranian-studied patients and homozygote c.1168G>A was the most frequent ASS1 gene mutation. Global neonatal screening for citrullinemia type 1 in Iran is recommended and certain mutations can be used for screening severe form in this population.

Three novel mutations in Iranian patients with Tay-Sachs disease.

BACKGROUND: Tay-Sachs disease (TSD), or GM2 gangliosidosis, is a lethal autosomal recessive neurodegenerative disorder, which is caused by a deficiency of beta-hexosaminidase A (HEXA), resulting in lysosomal accumulation of GM2 ganglioside. The aim of this study was to identify the TSD-causing mutations in an Iranian population. METHODS: In this study, we examined 31 patients for TSD-causing mutations using PCR, followed by restriction enzyme digestion. RESULTS: Molecular genetics analysis of DNA from 23 patients of TSD revealed mutations that has been previously reported, including four-base duplications c.1274_1277dupTATC in exon 11 and IVS2+1G>A, deletion TTAGGCAAGGGC in exon 10 as well as a few novel mutations, including C331G, which altered Gln>Glu in HEXB, A>G, T>C, and p.R510X in exon 14, which predicted a termination codon or nonsense mutation. CONCLUSION: In conclusion, with the discovery of these novel mutations, the genotypic spectrum of Iranian patients with TSD disease has been extended and could facilitate definition of disease-related mutations.

Effects of miglustat on stabilization of neurological disorder in niemann-pick disease type C: Iranian pediatric case series.

Niemann-Pick disease type C is a rare neurodegenerative disorder with autosomal recessive inheritance that can be broadly categorized into different forms dependent on age at disease onset: pre-/perinatal, early infantile, late infantile, juvenile, and adolescent/adult. This study was conducted to define the age at onset, clinical manifestations, neuroimaging findings and response to treatment in 21 patients diagnosed with Niemann-Pick disease type C and managed in the neurology departments of hospitals in Tehran, Iran. The effects of miglustat on patient ambulation, fine and gross motor function, swallowing, hearing, speech, seizures, psychomotor development, and ocular movements were evaluated for up to 26 months of treatment. Ambulation, fine and gross motor movements, swallowing, speech, and supranuclear gaze palsy were generally stabilized during therapy, and psychomotor delay appeared to be improved in early- and late-infantile onset patients. However, miglustat had no effect on organomegaly or other systemic manifestations of the disease. Miglustat was well tolerated.

Methylmalonic acidemia: brain imaging findings in 52 children and a review of the literature.

BACKGROUND: Methylmalonic acidemia (MMA) is an autosomal-recessive inborn error of metabolism. OBJECTIVE: To recognize the CT and MR brain sectional imaging findings in children with MMA. MATERIALS AND METHODS: Brain imaging studies (47 MR and 5 CT studies) from 52 children were reviewed and reported by a neuroradiologist. The clinical data were collected for each patient. RESULTS: The most common findings were ventricular dilation (17 studies), cortical atrophy (15), periventricular white matter abnormality (12), thinning of the corpus callosum (8), subcortical white matter abnormality (6), cerebellar atrophy (4), basal ganglionic calcification (3), and myelination delay (3). The brain images in 14 patients were normal. CONCLUSION: Radiological findings of MMA are nonspecific. A constellation of common clinical and radiological findings should raise the suspicion of MMA.

A Child with elemental mercury poisoning and unusual brain MRI findings.

Mercury vapor poisoning is a serious and potentially fatal problem. Neurological manifestations involving the central nervous system are seen with chronic mercury intoxication. We present the case of a 10-year-old child who demonstrated acrodynia, seizures, and visual impairment following 20 days of exposure to elemental mercury at home. The initial blood mercury concentration was 27.7 microg/L (normal <2 microg/L) and the initial 24-hour urine mercury concentration was 34.4 microg/L (normal =10 microg/L). After 9 months of treatment with D-penicillamine, the patient's clinical condition, biochemical laboratory parameters, and mercury concentrations all returned to normal. The T2-weighted MRI images of the patient's brain initially showed multiple hyperintense lesions in cerebral white matter, left globus pallidus, and putamen, which also improved.