OVERVIEW

REVEAL

Hereditary metabolic disorders are defined as multisystemic diseases that cover a wide spectrum of more than 1,000 different disorders. Their prevalence ranges from 1 in 200 to very rare (<1 in 1,000,000). Metabolism is the motor for all vital processes in the human body. It includes the build-up (anabolism), breakdown (catabolism), and conversion (amphibolism) of various substances that are needed to build up and maintain body tissue and generate energy.

Changes in the genes of the metabolic pathway can lead to the accumulation of metabolites, metabolic intermediates, or toxic substances, the production of unusual metabolites, or the defective transport of certain substances. This can cause a variety of symptoms which usually manifest shortly or within weeks after birth. However, they can also progress slowly over the years and develop later in life.

Our tests combine biochemical tests and gene tests (single-gene, gene panels and a comprehensive panel) associated with many different metabolic disorders, providing a complete diagnostic solution.

TREAT

Genetic testing can help to uncover the cause of persistent and/or debilitating symptoms. Identifying the disease-causing variant can help to decide on an appropriate and essential treatment that can prevent or reduce symptoms, avoid chronic health consequences and improve quality of life.

IMPORTANCE OF GETTING TESTED

The wide spectrum of symptoms and the varying age of onset make diagnosing a metabolic disorder challenging and time-consuming. Genetic testing can detect genetic changes, thereby, helping to identify metabolic diseases. Based on the diagnosis, appropriate treatment and clinical management can be chosen and a prognosis can be estimated. Additionally, family members can be tested.

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You have common symptoms
of a metabolic disease

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You have a spectrum of
overlapping symptoms that
vary in age of onset and severity

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You have neurological symptoms
that haven’t improved
with routine therapies

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You have a family history
of a metabolic disease

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Your newborn has abnormal
newborn screening results

OUR TESTS

We offer a comprehensive solution combining biochemical tests and genetic tests.

CLINICAL LAB TESTS

Basic laboratory, including blood pressure, blood sugar, cholesterol, triglyceride levels, blood gas analysis (BGA), including pH, glucose, lactate, blood ammonia, urinary ketones, liver enzymes, etc.

Specific laboratory for metabolic disease, including amino acids in serum, organic acids in urine, acylcarnitine, and enzyme functional assays.

GENETIC TESTS

Based on the biochemical findings, genetic analysis may be recommended. Your physician can choose from gene panels or a single comprehensive gene panel (Evartia).

Our genetic tests include:
35 single-gene disorders
22 panels
1 comprehensive panel (Evartia)

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SINGLE-GENE DISORDERS

SyndromeGene
AbetalipoproteinemiaMTTP
ApoA-I deficiencyAPOA1
Biotinidase deficiencyBTD
Crigler-Najjar syndromeUGT1A1
Dihyropyrimidine dehydrogenase deficiencyDPYD
Fabry diseaseGLA
Fish-eye diseaseLCAT
Fructose intoleranceALDOB
Fructose-1,6-bisphosphatase deficiencyFBP1
GalactosemiaGALT
Gaucher diseaseGBA
Gilbert syndromeUGT1A1
Glucose-6-phosphate dehydrogenase deficiency (Favism)G6PD
Glutaric acidemia I (GA1)GCDH
Glycogen storage disease II (Pompe disease)GAA
Hepatic lipase deficiencyLIPC
Hereditary hemochromatosis (standard)HFE
Hypercholesterolemia / HypobetalipoproteinemiaAPOB
Hypercholesterolemia, familial (standard)APOB
HyperhomocysteinemiaMTHFR
Hyperlipoproteinemia, type IbAPOC2
Hyperlipoproteinemia, type IIIAPOE
Isovaleric acidemiaIVD
Krabbe diseaseGALC
Lactase deficiency, congenitalLCT
Lactose intoleranceLCT
Lipoprotein lipase deficiencyLPL
Medium-chain acyl-CoA dehydrogenase deficiency (MCAD)ACADM
Methylmalonic aciduriaMMUT
Mevalonic aciduriaMVK
PhenylketonuriaPAH
Smith-Lemli-Opitz syndromeDHCR7
Tangier diseaseABCA1
Tyrosinemia, type IFAH
Wilson diseaseATP7B
GENE PANELS

SyndromeNo. of genesGenes
Alcohol intolerance2ADH1B, ALDH2
Chylomicronemia syndrome5APOA5, APOC2, GPIHBP1, LMF1, LPL
Congenital disorders of glycosylation (CDGs)43ALG1, ALG11, ALG12, ALG13, ALG2, ALG3, ALG6, ALG8, ALG9, B4GALT1, CAD, CCDC115, COG1, COG4, COG5, COG6, COG7, COG8, DDOST, DOLK, DPAGT1, DPM1, DPM2, DPM3, MGAT2, MOGS, MPDU1, MPI, NGLY1, PGM1, PMM2, RFT1, SLC35A1, SLC35A2, SLC35C1, SLC39A8, SRD5A3, SSR4, STT3A, STT3B, TMEM165, TMEM199, TUSC3
Fatty acid oxidation disorders7ACADM, ACADVL, ETFA, ETFB, ETFDH, HADHA, HADHB
Hereditary hemochromatosis (extended)6BMP6, HAMP, HFE, HJV, SLC40A1, TFR2
Hypercholesterolemia, familial (extended)4APOB, LDLR, LDLRAP1, PCSK9
Hyperlipoproteinemia, mixed3APOA1, APOE, LIPC
Hyperoxaluria3AGXT, GRHPR, HOGA1
Hypertriglyceridemia5APOA5, APOC2, GPIHBP1, LMF1, LPL
Hypoalphalipoproteinemia3ABCA1, APOA1, LCAT
Hypobetalipoproteinemia4ANGPTL3, APOB, MTTP, PCSK9
Malignant hyperthermia2CACNA1S, RYR1
Maple syrup urine disease (MSUD)3BCKDHA, BCKDHB, DBT
Mitochondrial carnitine-acylcarnitine cycle disorders3CPT1A, CPT2, SLC25A20
MODY (Maturity-onset diabetes of the young)14ABCC8, APPL1, BLK, CEL, GCK, HNF1A, HNF1B, HNF4A, INS, KCNJ11, KLF11, NEUROD1, PAX4, PDX1
Mucopolysaccharidosis10ARSB, GALNS, GLB1, GUSB, HGSNAT, HYAL1, IDS, IDUA, NAGLU, SGSH
Niemann-Pick disease3NPC1, NPC2, SMPD1
Obesity11KSR2, LEP, LEPR, MC3R, MC4R, MRAP2, NTRK2, PCSK1, POMC, SH2B1, SIM1
Porphyrias8ALAD, ALAS2, CPOX, FECH, HMBS, PPOX, UROD, UROS
Propionicacidemia2PCCA, PCCB
Tay-Sachs disease (available from Q2/2021)2GM2A, HEXA
Urea cycle disorders8ARG1, ASL, ASS1, CPS1, NAGS, OTC, SLC25A13, SLC25A15

WHAT ARE THE SYMPTOMS OF HEREDITARY METABOLIC DISEASES?

Symptoms of hereditary metabolic diseases can vary with severity ranging from mild to severe. In most cases, they appear shortly after birth. However, depending on the mutation, the metabolic pathway involved and the severity of the condition, some people can develop symptoms in early or late adulthood. Importantly, adults and children with the same metabolic disorder may have different symptoms.

Additional symptoms may include vision disturbances, impaired kidney function, heart problems, abnormal movements, behavioral or learning issues, distinctive facial features, and recurrent infections.

Common symptoms may include:
Vomiting
Abdominal pain
Lethargy
Psychological or neurological symptoms
Weight loss
Seizures

MEDICAL GENETIC COUNSELLING

We provide expert medical genetic counselling as part of a genetic testing journey. Genetic counselling is a process of communication that supports patients and their relatives before and after genetic testing. It is educational, impartial and nondirective. Prior to any genetic test, genetic counsellors will obtain a detailed family history, explain the method of testing that will be used, its risks and benefits, the limitations of the diagnosis and the implications of making a genetic diagnosis (Elliott and Friedman, 2018, Nat Rev Genet 19:735).

Upon receiving the genetic test results, genetic counselling can help the specialist physician and the patient to interpret them. They can be advised of the consequences of the results including the probability of developing the genetic disorder or passing it on to children, as well as ways to prevent, avoid or reduce these risks (Yang and Kim, 2018, Ann Lab Med 38:291). Our goal of counselling is to provide the patient with greater knowledge and thus, a better understanding of the results and the ability to make a more informed decision.

POSSIBLE OUTCOMES OF THE TEST

A molecular genetic diagnostic report outlining the results of the sequencing analysis is provided. Changes in DNA sequences (variants) can be detrimental and lead to the development of a metabolic disorder. We will report pathogenic and likely pathogenic variants as well as variants of unknown significance.

Pathogenic and likely pathogenic variants mean the genetic cause of the observed symptoms has been identified and may help determine the right treatment and management plan.

Variants of unknown significance means there was not enough evidence to classify the variant as either pathogenic or neutral. Annual variant reclassification and testing family members is recommended.

It is important to note that a negative result does not guarantee the absence of a disorder or that the disorder does not have a genetic cause. Genetic testing is an evolving field and may not detect all variants or there may not currently be enough evidence to classify all variants that lead to an inherited disease.

HOW TO ORDER A TEST
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Ask your healthcare provider about Metabolic Disorders Reveal&Treat

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Your healthcare provider will collect the sample using a buccal swab

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The sample will be sent to our laboratory

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The sample will be analyzed in our laboratory

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Results will be sent to your healthcare provider within 2-4 weeks from sample receipt

ORDER FORM
ACCEPTED MATERIAL

2 ml EDTA blood

TURNAROUND TIME

15-25 working days

TECHNOLOGY

DNA is isolated and next generation sequencing is performed on all coding exons and conserved intronic regions. Single base pair changes, small deletions and duplications and copy number variants (CNV) are identified. Sequencing runs result in a Quality Score of >30 (accuracy >99.9%) in at least 75% of all bases with a coverage of >20-fold. CNV detection sensitivity is 76.99% and precision is 62.59% (with GC limitation between 0.4 and 0.6 per target sensitivity is 77.04% and precision is 84.10%). Variant classification is performed following ACMG guidelines (Richards et al. 2015, Genet Med 17:405; Kearney et al. 2011, Genet Med 13:680).

Test Methodology
Sequencing

Next generation
sequencing (Illumina)

Enrichment

Twist Human Core
Exome plus Ref Seq
Spikeln

SNV and CNV data anlaysis

Illumina DRAGEN
Bio-IT Platform

Data Evaluation

VarSeq by
GoldenHelix

Reference Genome

hg38, NCBI GR38

Quality Criteria

>30 (precision >99,9%)
in min. 75% of bases

SNV detection sensitivity

99.92-99.93%; confirmation of reported SNV with Sanger
sequencing, data analysis with
SeqPilot

Classification of variants

Richards et al. 2015, Genet Med
17:405; Ellard et al. “ACGS Best
Practice Guidelines for Variant
Classification 2020″

in silico algorithms

MaxEntScan,
SpliceSiteFinder-like,
REVEL

Databases

HGMD Professional
release, ClinVar,
gnomAD

OUR TESTS

Genes: ADH1B, ALDH2

Genes: APOA5, APOC2, GPIHBP1, LMF1, LPL

Genes: CYP11B1, CYP11B2, CYP17A1, CYP21A2, HSD3B2

Genes: ALG1, ALG11, ALG12, ALG13, ALG2, ALG3, ALG6, ALG8, ALG9, B4GALT1, CAD, CCDC115, COG1, COG4, COG5, COG6, COG7, COG8, DDOST, DOLK, DPAGT1, DPM1, DPM2, DPM3, MGAT2, MOGS, MPDU1, MPI, NGLY1, PGM1, PMM2, RFT1, SLC35A1, SLC35A2, SLC35C1, SLC39A8, SRD5A3, SSR4, STT3A, STT3B, TMEM165, TMEM199, TUSC3

Genes: UGT1A1

Genes: ACADM, ACADVL, ETFA, ETFB, ETFDH, HADHA, HADHB

Genes: GALT

Genes: BMP6, HAMP, HFE, HJV, SLC40A1, TFR2

Genes: APOB, LDLR, LDLRAP1, PCSK9

Genes: MTHFR

Genes: AGXT, GRHPR, HOGA1

Genes: APOA5, APOC2, GPIHBP1, LMF1, LPL

Genes: ANGPTL3APOBMTTPPCSK9

Genes: ALPL

Genes:

CLCN5DMP1ENPP1FAM20CFGF23PHEXSLC34A1SLC34A3SLC9A3R1

Genes: IVD

Genes: GALC

Genes: LCT

Genes: CACNA1S, RYR1

Genes: BCKDHA, BCKDHB, DBT

Genes: ABCC8, APPL1, BLK, CEL, GCK, HNF1A, HNF1B, HNF4A, INS, KCNJ11, KLF11, NEUROD1, PAX4, PDX1

Genes: MVK

Genes: ARSB, GALNS, GLB1, GUSB, HGSNAT, HYAL1, IDS, IDUA, NAGLU, SGSH

Genes: ACADM, ACADVL, BCKDHA, BCKDHB, BTD, CFTR, CPT1A, CPT2, CYP21A2, DBT, DUOX2, FAH, GALT, GCDH, HADHA, HADHB, IVD, PAH, PAX8, SLC25A20, TSHR

Genes: NPC1, NPC2, SMPD1

Genes: KSR2LEPLEPRMC3RMC4RMRAP2NTRK2PCSK1POMCSH2B1SIM1

Genes: PAH

Genes: ALAD, ALAS2, CPOX, FECH, HMBS, PPOX, UROD, UROS

Genes: PCCA, PCCB

Genes: ABCA1

Genes:

GM2AHEXAHEXB

Genes: FAH

Genes: ARG1, ASL, ASS1, CPS1, NAGS, OTC, SLC25A13, SLC25A15

Genes: ATP7B

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