Citrullinemia type I (CTLN1) is a rare autosomal recessive disorder of the urea cycle caused by a deficiency in the argininosuccinate synthetase (ASS1) enzyme due to mutations in the ASS1 gene. Only a few Chinese patients with CTLN1 have been reported, and ASS1 gene mutations have been identified sporadically in China.
A Chinese family with one member affected with mild CTLN1 was enrolled. Targeted exome sequencing was performed on the proband, and Sanger sequencing was used to validate the detected mutation. We also reviewed the genetic and clinical characteristics of CTLN1 in Chinese patients that have been published to date. Newborn screening showed remarkably increased concentrations of citrulline with elevated ratios of citrulline/arginine and citrulline/phenylalanine, and the patient presented with a speech delay at age three. The urinary organic acid profiles were normal. A novel homozygous splicing variant c.773 + 4A > C in the ASS1 gene was identified in the proband, and it was predicted to affect splicing by in silico analysis. To date, only nine Chinese patients with CTLN1 have been reported, with a total of 15 ASS1 mutations identified and no high frequency or hot spot mutations found; the mutation spectrum of Chinese patients with CTLN1 was heterogeneous.
We described a mild Chinese CTLN1 case with a novel homozygous splicing variant c.773 + 4A > C and reviewed previous genotypes and phenotypes in Chinese patients with CTLN1. Thus, our findings contribute to understanding the molecular genetic background and clinical phenotype of CTLN1 in this population.

An enzymatic abnormality of the urea cycle is a metabolic disorder occasionally seen in adults, but particularly in the puerperium. The main risk is acute hyperammoniemic encephalopathy, leading to psychosis, coma and even death if not diagnosed promptly and treated appropriately. Headache is frequent in the puerperium normally manifesting between 3 and 6 days after delivery. We describe here a 39-year-old woman, who 3 days after delivery presented diffuse tension-type headache and depression, followed by behavioral disorders, psychomotor agitation, epileptic seizures, and finally coma 2 days later. Pregnancy and normal delivery: routine blood chemistry findings, CT scan, MR imaging, angio-MR of the brain, and lumbar puncture were normal. EEG when seizures started, it showed diffuse slowing, as in the case of metabolic encephalopathy. This led us to assay blood ammonia, which was high at >400 mmol. Liver function and abdominal US were normal; hence, we suspected a urea cycle enzymatic abnormality, and requested for genetic tests. These confirmed a congenital primary metabolic deficiency of arginine succinate synthetase, with high citrullinemia (type II, adult form). Dialysis was started promptly, with initially iv arginine, then orally, plus medical therapy for the hyperammoniemia and a low protein diet; plasma ammonia dropped swiftly to normal, and her state of consciousness gradually improved until all the clinical symptoms had resolved. Ammonia assay should always be considered in the first few days of the puerperium in women with headache and behavioral disorders, to exclude an inborn deficiency of the urea cycle, which may have gone unnoticed until then.

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A 52-year-old heavy drinker presented with repeated episodes of disturbance of consciousness and an increase in serum ammonia level, triggered by excessive alcohol intake. He was diagnosed as having adult-onset citrullinemia with deficiency of hepatic argininosuccinate synthetase (ASS) activity. Cranial magnetic resonance imaging (MRI) showed high-intensity lesions in the central pons and the bilateral middle cerebellar peduncles on T2-weighted images. Although almost all cases of adult-onset citrullinemia have been reported to be enzymologically classified as type II, the serum amino acid pattern and serum level of human pancreatic secretory trypsin inhibitor (hPSTI) were atypical for type II in the present case.

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The present report describes a Chinese male who presented for the first time with recurrent encephalopathy and hyperammonaemia at the age of 52 years. He was found to have citrullinaemia. To our knowledge, this is the first Chinese with citrullinaemia and the first non-Japanese who has the variant form of presentation. The patient also has the longest asymptomatic period for citrullinaemia so far described. The patient\'s biochemical derangement, clinical features and the postulation of his late presentation are discussed. It is noteworthy that simple therapeutic measures, such as lactulose and dietary protein restriction, controlled his symptoms well.

A young adult patient suddenly began to have episodes of unconsciousness that each lasted for several hours. Brief episodes of lethargy occurred monthly. Biochemical tests disclosed high levels of ammonia and citrulline in the serum. Brain oedema was suggested by CT scan, and optic disc swelling was observed ophthalmoscopically, indicating papilloedema. He died in coma. Deficient activity of argininosuccinate synthetase in the liver was demonstrated. Papilloedema was confirmed histologically. We believe that papilloedema is a serious sign indicating poor prognosis in late-onset citrullinaemia.

We report a case of a 56 year old woman who presented with a long history of chronic attacks of vomiting. On admission to hospital she was cachectic, and attempted parenteral nutrition induced coma. The illness was found to be due to citrullinaemia, a metabolic disorder of the urea cycle. Our patient is the oldest with this disorder so far described in the literature. The main points of the case and its investigation are outlined: hyperammonaemia, amino acid chromatogram, measurement of enzyme activity in skin and liver biopsy material. The therapeutic measures which led to cure are of particular interest.

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A 24-year-old man was admitted to our hospital, because two days before the admission he had abruptly lost consciousness following generalized convulsive seizures. He had a past history of transient amnesia and a favor for peanuts. His grandparents had a record of consanguinity. On admission, he was comatose and flaccid with his four extremities. Laboratory examination revealed the followings; mild degree of abnormal liver function, slight elevation of blood ammonia, irregular theta basic rhythm on EEG, marked brain edema on CT and a normal liver ultrasonography. From the second hospital day, in addition to antiepileptic drugs and adrenocorticosteroids, branched chain amino acid was administered to reactivate damaged brain functions. Thereafter, the concentration of blood ammonia increased to more than 3,000 micrograms/dl, and as a result he fell into status epilepticus. On the fourth hospital day, the levels of citrulline in the plasma and urine taken on the first hospital day were found to have increased by 20 and 100 times, respectively. Although the transfusion of branched chain amino acid was stopped, he died while in coma on the 12th hospital day. Enzymatic analyses of necropsied liver specimens revealed that the quantitative activity of argininosuccinate synthetase had decreased to less than 10% in his urea cycle. In this patient, it was noted that, after transfusion of branched chain amino acid, his brain activities turned worse and blood ammonia was markedly elevated. There is a possibility that intravenous administration of branched chain amino acid may interrupt the urea cycle balance in an adult patient of citrullinemia with dysfunction of the brain, kidney and muscle, especially with brain edema.(ABSTRACT TRUNCATED AT 250 WORDS)