UCSD Biochemical Genetics Laboratory

Following is a list of tests offered by our laboratory. See also our shipping instructions and other information.

Tests and Specimens

The following pages summarize the individual tests and specify the sample requirements, turn-around times and prices.

URINE METABOLIC SCREEN (Urine)

Comments: The urine "screen" consists of a series of rapid, qualitative tests to detect metabolites suggestive of a few defined diseases. By definition, it is intended to identify patients who should have further testing; it is by no means exhaustive, and no screen can "rule out metabolic disease." Positive results of a screen should always be confirmed with specific quantitative tests. Our screen consists of the following individual tests, which might suggest the listed diagnoses (among others):

Sample requirements: Urine, 10-20 ml (minimum 5 ml), frozen without preservatives and shipped frozen (packed with dry ice) or lyophilized and shipped at room temperature with original volume specified.

Turn-around time: Routine: 2 days, Stat: 1 day.

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QUANTITATIVE AMINO ACID ANALYSIS (Urine, Plasma, Cerebrospinal Fluid)

Comments: Standard analysis using modern automated amino acid analyzer. We will resolve any ambiguities using an independent, two column analyzer. Please be aware that for accurate determination of homocysteine in blood, special handling is required you may call our lab to arrange specifically for plasma homocysteine.

Sample requirements: Urine, 10-20 ml (minimum 5 ml), frozen without preservatives and shipped frozen (packed with dry ice), or lyophilized and shipped at room temperature with original volume specified.
Plasma, ³1 ml from heparinized blood (green top tube) supernatant from clinical centrifugation (within 20 minutes) promptly frozen and shipped frozen (packed with dry ice) or lyophilized and shipped at room temperature with original volume specified.
Cerebrospinal fluid, ³1 ml (standard plastic LP tube or transferred to red top tube), frozen and shipped frozen (packed with dry ice).

Turn-around time: Routine: 3 days, Stat: same day.

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QUANTITATIVE ORGANIC ACID ANALYSIS (Urine, Plasma, Cerebrospinal Fluid)

Comments: Our organic acid analysis is based on a state-of-the-art application of gas chromatography-mass spectrometry. Identification of metabolites is definitive, and we fully quantitate more than 150 compounds. Note that other laboratories may give qualitiative results only or report results without mass spectral identification, which can lead to serious misinterpretation.

Sample requirements: Urine, 10-20 ml (minimum 5 ml), frozen without preservatives and shipped frozen (packed with dry ice) or lyophilized and shipped at room temperature with original volume specified.
Plasma, ³1 ml from heparinized blood (green top tube) supernatant from clinical centrifugation (within 20 minutes) promptly frozen and shipped frozen (packed with dry ice) or lyophilized and shipped at room temperature with original volume specified.
Cerebrospinal fluid, ³1 ml (standard plastic LP tube or transferred to red top tube), frozen and shipped frozen (packed with dry ice).

Turn-around time: Routine: 5 days, Stat: 2 days.

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QUANTITATIVE OROTIC ACID ANALYSIS (Urine)

Comments: Orotic aciduria may be seen in deficiency of orotate decarboxylase, or following a single dose of allopurinol in females who are carriers for ornithine transcarbamylase deficiency. We use gas chromatography-mass spectrometry for definitive identification.

Sample requirements: Urine, 10-20 ml (minimum 5 ml), frozen without preservatives and shipped frozen (packed with dry ice) or lyophilized and shipped at room temperature with original volume specified.

Turn-around time: Routine: 5 days, Stat: 2 days.

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QUANTITATIVE N-ACETYLASPARTATE ANALYSIS (Urine)

Comments: Gross elevations of N-acetyl aspartate can be used to diagnose Canavan's disease. We use gas chromatography-mass spectrometry for definitive identification.

Sample requirements: Urine, 10-20 ml (minimum 5 ml), frozen without preservatives and shipped frozen (packed with dry ice) or lyophilized and shipped at room temperature with original volume specified.

Turn-around time: Routine: 5 days, Stat: 2 days.

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QUANTITATIVE METHYLMALONIC ACID (MMA) ANALYSIS (Urine, Plasma)

Comments: Quantitation of MMA excretion can be used to follow the clinical status and therapeutic response of patients with methylmalonic acidemia. We use gas chromatography-mass spectrometry for definitive identification and precise quantitation.

Sample requirements: Urine, 10-20 ml (minimum 5 ml), frozen without preservatives and shipped frozen (packed with dry ice) or lyophilized and shipped at room temperature with original volume specified.

Turn-around time: Routine: 5 days, Stat: 2 days.

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QUANTITATIVE CARNITINE ANALYSIS (Urine, Plasma, Tissue)

Comments: Carnitine is assayed using carnitine acyl transferase, with and without alkaline hydrolysis of esters. Reported values are total, free, and esterified carnitine.

Sample requirements: Urine, 10-20 ml (minimum 5 ml), frozen without preservatives and shipped frozen (packed with dry ice) or lyophilized and shipped at room temperature with original volume specified.
Plasma, ³1 ml from heparinized blood (green top tube) supernatant from clinical centrifugation (within 20 minutes) promptly frozen and shipped frozen (packed with dry ice) or lyophilized and shipped at room temperature with original volume specified.
Tissue, at least 1 gram muscle or liver, rapidly frozen at -70°C, stored and shipped frozen (packed with dry ice).

Turn-around time: Routine: 7 days, Stat: 3 days.

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QUANTITATIVE ANALYSIS OF BIOTIN (Urine, Plasma)

Comments: This radioimmunochemical assay is very sensitive.

Sample requirements: Plasma, 1 ml plasma from blood collected in EDTA (purple-top) or heparinized (green-top) tube, supernatant frozen and shipped frozen (packed with dry ice).
Urine, 1 ml stored frozen and shipped packed with dry ice.

Turn-around time: 2-3 days.

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BIOTINIDASE ACTIVITY (Serum, Plasma)

Comments: Our method of performing this radiochemical assay is original, using the natural substrate 3H-biocytin. Very small sample volumes required. Serum is preferred.

Sample requirements: Plasma, 1 ml (minimum 200 ml) from blood collected in EDTA (purple-top) or heparinized (green-top) tube, supernatant frozen and shipped packed with dry ice.
Serum, 1 ml (minimum 200 ml) from blood collected in plain (red-top) tube, supernatant frozen and shipped packed with dry ice.

Turn-around time: Routine: 1 week, Stat: 2 days.

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CARBOXYLASE ACTIVITIES (PYRUVATE, PROPIONYL-COA, AND 3-METHYLCROTONYL-COA CARBOXYLASES)
(Lymphocytes, Fibroblasts, Amniocytes)

Comments: These are radiochemical assays performed on cultured cells or isolated lymphocytes. For assay of lymphocytes from a blood sample, please call to assure that staff is available, as the specimens must be processed stat upon arrival.

Sample requirements: Blood, 3-5 ml in ACD (yellow-top) tube, kept at room temperature and shipped overnight at room temperature. For greater reliability, we request a simultaneous sample from a control individual (not a member of the patient's family).
Fibroblasts, Two T-25 flasks shipped overnight with medium at room temperature.
Prenatal diagnosis is possible with Amniocytes: Please call lab to coordinate.

Turn-around time: Routine: 5 days, Stat: 2 days (not including growing cultured cells, if required).

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HOLOCARBOXYLASE SYNTHETASE (Lymphocytes, Fibroblasts, Amniocytes)

Comments: These is a radiochemical assay performed on cultured cells or isolated lymphocytes. For assay of lymphocytes from a blood sample, please call to assure that staff is available, as the specimens must be processed stat upon arrival.

Sample requirements: Blood, 3-5 ml in ACD (yellow-top) tube, kept at room temperature and shipped at room temperature overnight. For greater reliability, we request a simultaneous sample from a control individual (not a member of the patient's family).
Fibroblasts, Two T-25 flasks shipped overnight with medium at room temperature.
Prenatal diagnosis is possible with Amniocytes: Please call lab to coordinate.

Turn-around time: Routine: 5 days, Stat: 2 days (not including growing cultured cells, if required).

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QUANTITATIVE ANALYSIS OF 3-HYDROXYBUTYRATE (Blood)

Comments: Assay of 3-hydroxybutyrate can be valuable in determining adequacy of ketogenesis, particularly at a time of prolonged fasting or hypoglycemia. This is a very sensitive fluorometric assay, enabling monitoring of fasting ketogenesis with serial sampling of fingerstick volumes.

Sample requirements: Whole blood or Plasma, 0.5 ml (50 ml minimum), frozen and shipped on dry ice.

Turn-around time: Routine: 5 days, Stat: 2 days.

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QUANTITATIVE ANALYSIS OF ACETOACETATE (Blood)

Comments: Assay of acetoacetate can be valuable in determining adequacy of ketogenesis, particularly at a time of prolonged fasting or hypoglycemia, and the ratio of acetoacetate to 3-hydroxybutyrate may provide evidence of a defect of energy metabolism. This is a very sensitive fluorometric assay, enabling monitoring of fasting ketogenesis with serial sampling of small volumes. Since the compound is unstable, however, this test can only be performed for sites within our local area. Please call our lab at least one working day before samples are to be obtained, to assure that staff is available and that specimen transportation is arranged. Freeze sample promptly while awaiting transport.

Sample requirements: Whole blood or Plasma, 0.5 ml (50 ml minimum), frozen and shipped on dry ice.

Turn-around time: Routine: 5 days, Stat: 2 days.

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SET-UP OF FIBROBLAST CULTURE (Biopsy)

Comments: We can establish a culture of your patient's fibroblasts in order to assay in our lab or to convey to a reference lab for a particular assay or genetic test.

Sample requirements: Biopsy (skin or other specimen with adequate connective tissue), usually a single 3 or 4 mm diameter piece of skin extending to the epidermal-dermal junction is sufficient, kept in sterile medium at room temperature and shipped overnight.

Turn-around time: Variable, depending on sample origin and condition, generally 4-6 week minimum.

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HYPOXANTHINE-GUANINE PHOSPHORIBOSYL TRANSFERASE (Blood, Cultured Fibroblasts)

Comments: The diagnosis of Lesch-Nyhan syndrome and variant forms depends on the assay of HPRT. Our assay is radiochemical, and we also measure Adenine Phosphoribosyl Transferase as an internal control. It is helpful to have a clinical history of the patient provided.

Sample requirements: Whole blood, 3-5 ml in heparinized (green-top) tube. For greater reliability, we request a simultaneous sample from a control individual (not a member of the patient's family).
Cultured fibroblasts, 2 T-25 flasks shipped with sterile medium at room temperature overnight.
Amniocytes, Please call lab to coordinate.

Turn-around time: 5 days (not including growing cultured cells, if required).

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HYPOXANTHINE-GUANINE PHOSPHORIBOSYL TRANSFERASE FOR CARRIER DETECTION (Hair Roots)

Comments: To determine heterozygosity for female carriers of this X-linked disorder, distrubution of HPRT activity can be determined among individual hair root bulbs from the potential carrier. Statistical analysis indicates that analysis of ³30 hair roots can exclude carrier status to a certainty of 98%.

Sample requirements: Hair roots, minimum of 30 bulbs in good condition. Storage and shipping at room temperature is adequate. Please call our lab for an instruction sheet on collection of hair roots.

Turn-around time: 1-2 weeks.

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OXYPURINE QUANTITATION (Urine)

Comments: The ratio of excretion of the oxypurines (hypoxanthine, xanthine, uric acid) may be used to distinguish among conditions of hypouricemia (renal tubular wasting vs xanthine oxidase, molybdenum cofactor deficiency, etc.), and to monitor therapy in hyperuricemia conditions (e.g. gout and Lesch-Nyhan syndrome). We use an electrochemical HPLC method to obtain ratios of the oxypurines to creatinine.

Sample requirements: Urine, 10 (min 5) ml frozen urine.

Turn-around time: 2-8 weeks.

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SUCCINYLPURINE SCREEN (Urine)

Comments: Succinylpurine products (succinylAICAriboside and succinyladenosine) are elevated in the body fluids of patients with deficiency of adenylosuccinate lyase, a disorder which can present with mental retardation, seizures and autistic features. We use the colorimetric method of Bratton & Marshall to screen for succinylAICAriboside, and then HPLC to confirm suspected cases. Please do not send specimens from patients taking sulfa antibiotics, as SULFA DRUGS CAUSE FALSE POSITIVES.

Sample requirements: Urine, filter paper pad (³ 1 × 1 cm) soaked with urine and dried (will suffice for colorimetric screen ONLY), and/or
Urine, 10-20 ml (min 2) frozen and shipped on dry ice or lyophilized and shipped at room temp with original volume specified (required if confirmatory HPLC analysis wanted).

Turn-around time: 2-8 weeks.

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SUCCINYLACETONE QUANTITATION (Urine, Plasma)

Comments: Succinylacetone excretion can be used to follow the clinical status and therapeutic response of patients with tyrosinemia (type 1, hepatorenal). We use gas chromatography-mass spectrometry for definitive identification and precise quantitation.

Sample requirements: Urine, 10-20 ml (minimum 5 ml), frozen without preservatives and shipped frozen (packed with dry ice) or lyophilized and shipped at room temperature with original volume specified.

Turn-around time: Routine: 5 days, Stat: 2 days.

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VERY LONG CHAIN FATTY ACIDS (Serum)

Comments: Very long chain fatty acids accumulate in all disorders of peroxisomal oxidation such as Zellweger syndrome or adrenoleukodystrophy, independent of the clinical condition of the patient. Therefore, measurement of these compounds in plasma allows identification of an inborn error of peroxisomal metabolism.

Sample requirements: Plasma, 2 ml from blood collected in EDTA (purple-top) tube. The test can not be done on whole blood. May be sent frozen or at room temperature, but if at room temperature, must arrive at laboratory within 2 days of collection. We recommend that the patient not have intravenous lipids for 2 days prior to collection.

Turn-around time: 1-2 weeks.

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MEDIUM CHAIN ACYL COENZYME A DEHYDROGENASE (MCAD) COMMON ALLELE DETECTION
(Blood, Tissue, or Extracted DNA)

Comments: MCAD is inherited as an autosomal recessive disorder which has been known to cause sudden infant death, hypoglycemia, and a Reyes-like syndrome. Approximately 90% of all affected individuals examined to date have been shown to be homozygous for the A®G 985 mutation in the MCAD gene. The test we offer is based on PCR analysis, and is specific for this mutation.

Sample requirements: Blood, 1 ml (minimum 250 ml) (in purple, or yellow-top tube or dried on small piece of clean filter paper). Blood should be frozen for storage, and may be sent frozen or at room temperature by overnight mail.

Turn-around time: 1-2 weeks.

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