Fumarylacetoacetate Hydrolase Knock-out Rabbit Model for Hereditary Tyrosinemia Type 1.

Hereditary tyrosinemia type 1 (HT1) is a severe human autosomal recessive disorder caused by the deficiency of fumarylacetoacetate hydroxylase (FAH), an enzyme catalyzing the last step in the tyrosine degradation pathway. Lack of FAH causes accumulation of toxic metabolites (fumarylacetoacetate and succinylacetone) in blood and tissues, ultimately resulting in severe liver and kidney damage with onset that ranges from infancy to adolescence. This tissue damage is lethal but can be controlled by administration of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), which inhibits tyrosine catabolism upstream of the generation of fumarylacetoacetate and succinylacetone.

Measurement of serum aldosterone in picomolar level by LC-MS/MS using charge-tagged technique.

Aldosterone is a mineralocorticoid steroid hormone, the measurement of which in the clinical laboratory is principally performed for the investigation of primary hyperaldosteronism. Primary hyperaldosteronism is a specifically treatable and potentially curable form of hypertension, which typically presents as drug-resistant hypertension and, in up to 37% of cases, hypokalemia. Accurate measurement of aldosterone concentration is essential for correct diagnosis.

Novel mutations in myopathic form of carnitine palmitoyltransferase II deficiency in a Chinese patient.

Background: Carnitine palmitoyltransferase II (CPT II) deficiency is one of the most common disorders of oxidative fatty acid metabolism. In this disorder, long-chain acylcarnitines cannot be converted to acyl CoA and there is impairment of β-oxidation of fatty acids.

Results: In the 3 distinct clinical subtypes of CPT II deficiency, adult onset myopathic form shows mild clinical manifestations, characterized by recurrent rhabdomyolysis after intense physical stress.

Biochemical and molecular diagnosis of tyrosinemia type I with two novel FAH mutations in a Hong Kong chinese patient: recommendation for expanded newborn screening in Hong Kong.

Objectives: Tyrosinemia type I is an autosomal recessive disorder in tyrosine metabolism. In areas without expanded newborn screening, patients present with acute hepatorenal failure in early infancy. Diagnosis can be elusive when clinical presentation is non-specific and biochemical abnormalities are masked by secondary changes.

Arginase deficiency with new phenotype and a novel mutation: contemporary summary.

In areas without expanded newborn screening, instead of presenting neonatally, patients with arginase deficiency typically present with spastic paraplegia in early childhood. Diagnosis of this rare neurometabolic disease poses the first challenge because it is often misdiagnosed as cerebral palsy during initial stages. We describe arginase deficiency in a 20-year-old woman with spastic paraplegia, progressive dystonia, dementia, peripheral neuropathy, epilepsy, liver cirrhosis, and non-B/non-C hepatocellular carcinoma.

Molecular diagnosis for a fatal case of very long-chain acyl-CoA dehydrogenase deficiency in Hong Kong Chinese with a novel mutation: a preventable death by newborn screening.

Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is one of the most common fatty acid oxidation defects that cause sudden unexpected deaths in infants. The death attributed to VLCAD deficiency can be prevented by early diagnosis with expanded newborn screening using tandem mass spectrometry. A favorable outcome can be achieved with early diagnosis and prompt treatment.

Metformin-associated lactic acidosis in Chinese patients with type II diabetes.

Metformin is a widely used antidiabetic agent that is generally considered safe. However, metformin-associated lactic acidosis (MALA), though not common, occurs from time to time and results in significantly high mortality. A series of 23 MALA cases in a local major hospital in Hong Kong is reported in this article to demonstrate the epidemiological data, risk factors, clinical features as well as the clinical outcomes for better understanding of this disease entity.

Non-invasive urinary screening for aromatic L-amino acid decarboxylase deficiency in high-prevalence areas: a pilot study.

Background: The diagnosis of aromatic L-amino acid decarboxylase (AADC) deficiency, one of the pediatric neurotransmitter disorders, is classically made with plasma enzyme level or cerebrospinal fluid (CSF) neurotransmitter profile, while both are technically demanding and the latter requires the invasive lumbar puncture. So far less than 100 cases have been reported worldwide with 20% from Taiwan. It was postulated that the condition might have been under-diagnosed among Chinese populations and a non-invasive screening tool should be developed in areas with high prevalence.

Fatal viral infection-associated encephalopathy in two Chinese boys: a genetically determined risk factor of thermolabile carnitine palmitoyltransferase II variants.

Influenza-associated encephalopathy (IAE) is a potentially fatal neurological complication of influenza infection usually in the presence of high and persistent fever. Thermolabile carnitine palmitoyltransferase II enzyme (CPT-II) predisposes IAE, so far only described in Japanese. As the genetic origins of Japanese and Chinese are alike, similar genetic risk factors in CPT-II are expected.

Analysis of inborn errors of metabolism: disease spectrum for expanded newborn screening in Hong Kong.

Background: Data of classical inborn errors of metabolism (IEM) of amino acids, organic acids and fatty acid oxidation are largely lacking in Hong Kong, where mass spectrometry-based expanded newborn screening for IEM has not been initiated. The current study aimed to evaluate the approximate incidence, spectrum and other characteristics of classical IEM in Hong Kong, which would be important in developing an expanded newborn screening program for the local area.

Methods: The laboratory records of plasma amino acids, plasma acylcarnitines and urine organic acids analyses from year 2005 to 2009 inclusive in three regional chemical pathology laboratories providing biochemical and genetic diagnostic services for IEM were retrospectively reviewed.

Role of postmortem genetic testing demonstrated in a case of glutaric aciduria type II.

Glutaric aciduria type II, or multiple acyl-CoA dehydrogenase deficiency, is a rare metabolic disorder inherited in an autosomal recessive manner. The condition can be caused by mutations in at least 3 genes, including ETFA, ETFB, and ETFDH. When this potentially lethal disorder is known for its clinical and biochemical heterogeneity, mutation analysis will be an invaluable part of diagnosis.

Analysis of melamine cyanurate in urine using matrix-assisted laser desorption/ionization mass spectrometry.

Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) was applied to the direct analysis of melamine cyanurate (MC). The three commonly used MALDI matrixes, namely, alpha-cyano-4-hydroxycinnamic acid (CHCA), sinapinic acid (SA), and 2,5-dihydroxybenzoic acid (DHB), were able to desorb/ionize melamine from MC upon N(2) laser irradiation, with CHCA showing the highest detection sensitivity in the positive mode. Only DHB and SA were able to desorb/ionize cyanuric acid from MC in the negative mode but with remarkably lower sensitivity.

Multi-elements (aluminium, copper, magnesium, manganese, selenium and zinc) determination in serum by dynamic reaction cell-inductively coupled plasma-mass spectrometry.

Background: Trace element determination in laboratory medicine is widely carried out by atomic absorption or emission spectroscopy. In the last decade, there has been a rapid growth in the use of inductively coupled plasma-mass spectrometry because of its strong detection power, and the possibility of multi-elements analysis in a single run.

Methods: Having the advantages of smaller sample volume and better detection limit, we developed a method for the simultaneous determinations of six trace elements by using 100 microL serum, and the assay can be accomplished within 3 min.

Determination of mercury in whole blood and urine by inductively coupled plasma mass spectrometry.

The conventional method for the determination of mercury in clinical samples is cold vapor atomic absorption spectrometry. Sample digestion or pretreatment require large sample volume and long sample preparation time. The inductively coupled plasma mass spectrometry (ICP-MS) method developed in this study requires only 100 microL of sample with practically no preparation, except for dilution with diluent.

Cough mixture abuse as a novel cause of folate deficiency: a prospective, community-based, controlled study.

Cough mixture abuse has been reported to cause severe folate deficiency and neurological defects. We carried out a prospective case-controlled survey to confirm this association and define the incidence and severity of the problem. A total of 57 cough mixture abusers and 47 other substance abusers (controls) were studied.