Disorders include amino acidopathies, organic acidurias, fatty acid oxidation defects, mitochondrial cytopathies, inborn errors of cholesterol biosynthesis, and creatine deficiency syndromes.

Biochemical Genetics Tests Offered at Kennedy Krieger Institute:

Amino Acid Analysis

Free amino acid concentrations are determined in biological samples by cation-exchange chromatography. Amino acid profiles are useful in assessing a variety of physiological and pathological conditions, including the diagnosis of certain inborn errors of amino acid metabolism. This testing is often used to confirm amino acid abnormalities identified by newborn screening.

Organic Acids

This test provides a qualitative and semi-quantitative evaluation of organic acids in urine or CSF by gas chromatography/mass spectrometry of trimethylsilyl ester/ether derivatives of solvent extracted acids using C 11 dioic acid as an internal standard. Organic acid analysis is useful for the diagnosis of certain disorders of amino and organic acid metabolism, including disorders affecting the metabolism of the branched-chain amino acids, tyrosine, lysine, and propionate as well as defects of the Krebs cycle, fatty acid beta-oxidation, and mitochondrial energy metabolism. This test is often required to evaluate abnormal newborn screening results.

Organic Acid Quantification by Stable Isotope Gas Chromatography/Mass Spectrometry

Quantification of organic acids by stable isotope gas chromatography/mass spectrometry is a sensitive and accurate alternative to organic acid screening for specific analytes. The Kennedy Krieger Institute Biochemical Genetics Laboratory provides this analysis for the following organic acids:

IEM/Physiological Condition Analyte Specimen Types
Canavan Disease N-Acetylaspartic acid Urine, Amniotic Fluid
Barth syndrome Mitochondrial Dysfunction 3-Methylglutaconic Acid Plasma, Urine
Inborn Errors of Methylmalonate/Cobalamin Metabolism; Vitamin B12 deficiency Methylmalonic Acid Plasma, Urine
Urea Cycle Defects Orotic Acid Urine
Mevalonic Aciduria Hyper IgD Syndrome (HIDDS) Mevalonic Acid Urine


Creatine Deficiency Syndromes

This test provides quantification of guanidinoacetic acid and creatine by isotope-dilution negative chemical ionization mass spectrometry for the diagnosis of creatine deficiency syndromes, a group of disorders with phenotypic presentations varying from cognitive and expressive speech/language delays to more severe presentations that may include dystonia, extrapyramidal symptoms, hypotonia, ataxia, seizures, and autistic-like behaviors.

Disorder Specimen Types
AGAT Deficiency Plasma (preferred), Urine
GAMT Deficiency Plasma (preferred), Urine
Creatine Transporter Deficiency Urine (fasting sample preferred)


Sterol Quantification by Selected Ion Monitoring Gas Chromatography/Mass Spectrometry

Quantification of 7-dehydrocholesterol and related sterols in biological specimens is used for the diagnosis of various inborn errors of cholesterol biosynthesis listed below. While the clinical presentation of individual sterol disorders is distinct, common features in many of these disorders include two or more of the following:

  • Distinctive facial features
  • Hypotonia
  • Micro/Macrocephaly
  • Intellectual Disability
  • Learning/Behavioral Problems
  • Developmental delays
  • Hypospadias/Ambiguous Genitalia
  • Cataracts
  • Bone Shortening and/or Asymmetry
  • Stippled Epiphyses
  • Icthyosis/Alopecia/Erythematous Rash
  • 2,3-Toe Syndactyly
  • Postaxial Polydactyly
  • Cleft Palate
  • Agenesis of the corpus callosum

A disorder of bile acid biosynthesis, cerebrotendinous xanthomatosis, and a disorder of plant sterol excretion, sitosterolemia, can also be identified by this analysis:


Disorder Diagnostic Analyte(s)
Smith-Lemli-Opitz Syndrome ↑7-Dehydrocholesterol
  N - ↓ Cholesterol
Desmosterolosis ↑ Desmosterol
Lathosterolosis ↑ Lathosterol
X-Linked Dominant Conradi Hünermann Syndrome (CDPX2) ↑ 8(9)-Cholestenol
C4-Methyl Oxidase (SC4MOL) Deficiency ↑ Mono-Methyl and Di-Methyl Sterols
Lanosterol Demethylase Deficiency ↑ Lanosterol and Dihydrolanosterol
Cerebrotendinous Xanthomatosis (CTX) ↑ Cholestanol + Multiple Cholesterol Precursors
Sitosterolemia ↑ Sitosterol and Campesterol
  • Testing may be performed by special arrangement for other inborn errors of cholesterol biosynthesis including CHILD syndrome and Greenberg dysplasia.

Carnitine, Free and Total

Free and total carnitine concentrations are determined in plasma using multiple reaction monitoring (MRM) tandem mass spectrometry and are useful for the identification of primary and secondary carnitine deficiency.

Acylcarnitine Profile

Acylcarnitine concentrations are determined in plasma by tandem mass spectrometry. Assessment of acylcarnitine profiles is useful for the diagnosis of certain disorders of fatty acid beta-oxidation and organic acid metabolism and is often required to confirm abnormal newborn screening results.

*Prenatal Testing by analyte quantification is available for the following disorders:

  • Smith-Lemli-Opitz Syndrome: amniotic fluid supernatant or direct chorionic villus
  • Canavan Disease: amniotic fluid supernatant collected after 17 weeks gestation

Note: We do not provide prenatal testing in cultured amniocytes or cultured chorionic villi.