# Presentation: 429230

## Biochemical & Molecular Collaborations

** **

**Disclaimers: **

**I am not a biochemical geneticist.**

**2.  I am not a molecular geneticist.**

**I am a clinical cytogeneticist who has **
**    ****seen the benefits of collaborations **
**    ****between cyto and DNA labs.**

## Cytogenetics-Molecular Transitions & Collaborations

**Fragile X testing moved from Cyto->Molec, but still need cyto for neg. results in DD/MR**
**PWS**
**methylation best r/o test (low index suspicion); **
**FISH best if PWS dx likely**
**UPD testing important if FISH negative**
**karyotype important if all negative**
**	**
**	**

## Cytogenetics-Molecular Transitions & Collaborations

**FISH has become important adjunct to banding, but has not replaced banding**
**aCGH will become important adjunct or perhaps primary diagnostic platform, but will not completely replace banding or FISH**
**	**
**	**

## Biochemical-Molecular Transitions & Collaborations

_***Not***_** a proposal to **_***replace***_** ****biochemical testing with molecular testing**
**Biochemical testing of probands more cost-effective in most cases **
**high % “rule-out” referrals that will be mutation negative**
**Carrier detection and prenatal diagnosis often only available or more accurate by molecular methods (specific mutation known)**
**	**
**	**

## Biochemical-Molecular Applications

**Proband            Carrier        Prenatal Dx**

**Biochem             +++                    +/-                    ?      **

**Molecular             +/-                     ++                  ++    **

**Family**

**Is there adequate emphasis in our counseling**
**on family benefits to molecular testing?**

## Emory Genetics Laboratories

**Long history of biochemical genetics testing, now supplemented by molecular genetics laboratory**
**Full gene sequencing available for:**
**Galactosemia (GALT gene)**
**PKU**
**MSUD**
**MCADD**
**Developing full gene sequencing for all lysosomal storage diseases **
**Developing comprehensive biochemical and molecular testing (full gene sequencing) for all disorders on NBS Uniform Panel**
**	**
**	**

## Galactosemia – Comprehensive Diagnostic Panel

**Galactosemia – Comprehensive Diagnostic Panel**

## MCAD Deficiency

**DNA ANALYSIS RESULTS**
- Lys304Glu (K304E)     1 copy
- Tyr42His (Y42H)         negative
**INTERPRETATION**: This patient tested positive for one copy of the K304E MCAD mutation. Sequencing of the *ACADM* gene is recommended to identify the other mutation for family counseling and management.

**Abnormal**. The patient tested positive for one copy of the K304E mutation in the Medium Chain Acyl CoA Dehydrogenase (*ACADM*) gene. This result does not rule out a diagnosis of MCAD deficiency. Genetic counseling is recommended.

**MCAD Common Mutation Panel**

**Abnormal.**  In this plasma sample, the concentration of C8 was markedly elevated with elevated C6, C10:1 and C10, the ratio of C8/C10 was also significantly elevated (9.9, normal <2).  This profile is consistent with biochemical diagnosis for Medium Chain AcylCoA Dehydrogenase deficiency.  Recommend mutation analysis and immediate follow up with metabolic clinic.

- H

- 0 - 0.17

- 0.79

- Hexanoylcarnitine, C6

**Comment**

**Normal range**

**umol/L**

** ****Acylcarnitine **
**                      ****Age Group: AR1:Newborn, <  8 Days**

**Method: LC MS/MS**

**Acylcarnitine Profile, Plasma                      **

**MCAD Deficiency**