# Presentation: 334325

## Presentation to the ICD-9-CM Coordination and Maintenance Committee

- Dr. MG Blitzer on behalf of the American College of Medical Genetics
- 12/5/2003

## Metabolic Disorders

- Over the last decade, our understanding, diagnostic ability and treatment options for inherited metabolic disease has increased markedly.
- Several groups of potentially treatable disorders identified that are not uncommon:
- Fatty Acid Oxidation disorders
- Peroxisomal disorders
- Mitochondrial disorders

## Rationale for New Codes

- New disorders are now recognized that, in aggregate, are not uncommon
- More frequent than more familiar diseases such as PKU, galactosemia and Tay-Sachs disease.
- There are now specific diagnoses for numerous disorders but no specific codes.
- Many of these disorders are now screened for by newborn testing.

## FATTY ACID OXIDATION

- Plays a major role in energy production during periods of fasting
- Does not occur in the brain
- Many different steps involved in metabolic pathway – defects in any of these can result in a metabolic disorder

## FATTY OXIDATION DISORDERS(Clinical/Lab Findings)

- Typically present at a young age but can occur at any age, including adulthood
- Occurs at least as frequently as PKU
- Following fasting or viral infection, may present with episodes of vomiting, hypotonia, lethargy, hypoglycemia and coma –> life-threatening
- Some disorders result in chronic progressive muscle weakness, cardiomyopathy, or congenital anomalies.

## MCADD

- Medium Chain Co-A Acyl-Dehydrogenase Deficiency – Prototype for FAO disorders
- Incidence ~1:15,000 Northern European
- 25-50% first episode fatality rate
- Avoid Prolonged Fasting, _+_ Carnitine
- Requires new methodology for identification for diagnosis
- Tandem Mass Spectrometry

## PEROXISOMES

- Single membrane organelles within cell
- Both anabolic and catabolic functions
- Cholesterol and bile acid biosynthesis
- Metabolism of very long-chain fatty acids
- H2O2 metabolism
- Disorders result from defects in the formation or functioning of peroxisomes

## Examples of Peroxisomal Disorders

**Zellweger syndrome – biogenesis defect**
**X-linked adrenoleukodystrophy –single protein defect**
**“****Lorenzo’s Oil”**
**Rhizomelic chondrodysplasia punctata – skeletal disorder**

## Mitochondrial Disorders

- Mitochondria are cellular organelles involved in energy production and utilization
- Have their own DNA; disorders result from defects in mtDNA or nuclear DNA
- Disorders are many and varied
- Neurological involvement: myopathies and encephalopathies

## New Code Recommendations

- Under 277.8 Other specified disorders of metabolism
**New code: **_**277.85 Disorders of fatty acid oxidation**_
- Carnitine palmitoyltransferase deficiencies (CPT1,CPT2)
- Glutaric aciduria type II (type IIA, IIB, IIC)
- Long chain/very long chain acyl CoA dehydrogenase deficiency (LCAD, VLCAD)
- Long chain 3-hydroxyacyl CoA dehydrogenase deficiency (LCHAD)
- Medium chain acyl CoA dehydrogenase deficiency (MCAD)
- Short chain acyl CoA dehydrogenase deficiency (SCAD)
- Add  _Excludes: primary carnitine deficiencies (277.81)_

## New Code Recommendations

- Under 277.8 Other specified disorders of metabolism
**New Code: **_**277.86 Disorders of peroxisomal disorders**_
- Adrenomyeloneuropathy
- Infantile Refsum disease
- Neonatal adrenoleukodystrophy
- Rhizomelic chondrodysplasia punctata
- X-linked adrenoleukodystrophy
- Zellweger syndrome

## New Code Recommendations

**New Code: **_**277.87 Disorders of mitochondrial **_**	****	****	****   **_**metabolism**_
- Kearns-Sayre syndrome
- Mitochondrial encephalopathy, lactic acidosis and stroke-like episodes syndrome (MELAS)
- Myoclonus with epilepsy and with ragged red fibers syndrome (MERFF)
- Mitochondrial neurogastrointestinal encephalopathy (MNGIE)_
- Neuropathy, ataxia and retinitis pigmentosa syndrome (MARP)
- Add  _Excludes:_ 	_disorders of pyruvate metabolism (271.8)_
- 				_Leber’s disease (377.16)_
- 				_Leigh’s encephalopathy (330.8)_
- 				_Reye’s syndrome (331.81)_

## Autosomal Deletion Syndromes

- Autosomal: involves one of the numbered (ie, non-sex chromosomes)
- Deletion: an abnormality of DNA that involves missing material.  These can range from very small (as little as 1 base pair) to very large (involving millions of base pairs of DNA)

## Autosomal Deletion Syndromes

- Recommendations for ICD-9-CM
- Remove antimongolism (this is archaic and pejorative term, not clinically relevant)
- Add subcodes within 758.3
- 758.31 Cri-du-Chat (currently listed under 758.3)
- 758.32 Velo-Cardio-Facial Syndrome
- 758.33 Other microdeletions (with Smith-Magenis syndrome and Miller-Dieker syndrome listed)
- 758.39 Other autosomal deletions

## Cri-du-Chat syndrome

- First recognized syndrome due to a deletion (1963)
- Involves a missing piece of the short arm of chromosome 5 (5p-)
- Only deletion syndrome currently listed in ICD-9-CM

## Cri-du-Chat syndrome

- Mental retardation
- Microcephaly
- Round face
- Congenital Malformations
- Laryngeal anomaly leading to cry sounding like cat (infants)

- Picture from Cri-du-Chat Syndrome Website

## Cri-du-Chat syndrome

## Velo-Cardio-Facial Syndrome

- Abnormalities of palate including clefts (velo)
- Cardiac malformations (frequently septal defects)
- Unusual facial features
- Long face
- Flattened cheeks
- Dark circles under eyes
- Prominent nose

## Velo-Cardio-Facial SyndromeOther Features

- Learning disabilities/Mental retardation
- Long slender fingers
- Neuropsychiatric abnormalities
- Can be associated with DiGeorge sequence (T-cell immune deficiency, hypercalcemia)
- Caused by deletion 22q11.2

## Velo-cardio-facial SyndromeRationale for Including in ICD 9-CM

- Most common autosomal deletion syndrome (incidence in US ~1:3,000.
- Compare to Cri-du-chat 1:20-50,000)
- Nearly 100,000 affected in U.S.
- Well recognized syndrome diagnosed by geneticists, cardiologists, otolaryngologists
- Significant number diagnosed in adulthood

## Deletion vs. Microdeletion

- Deletion visible by standard cytogenetic techniques
- By definition is large (must be a minimum of 1-2 million bases to be visible)
- Usually severe birth defects, mental retardation and frequently shortened life

- Deletion requires special molecular techniques to detect
- Increasingly recognized as cause of specific syndromes
- As a whole are more common than visible deletions

## Example:Prader-Willi Syndrome

- Visible deletion
- Chromosome 15

- Microdeletion (absence of a FISH signal)

## Rationale for Separate Code

- Microdeletions are more common than visible deletions
- As more is learned and techniques are improving, more syndromes are found to be due to these microdeletions
- Specific molecular techniques are necessary to diagnose (specific code supports medical necessity for doing additional testing)
- Other conditions due to microdeletions can be added to index (Wolf-Hirschhorn, Jacobsen, etc)

## Routine Neonatal Screening

- Began in the 1960’s with PKU screening
- Is now expanding to include many metabolic conditions
- Is designed to maximize detection, therefore results in false positives

## Rationale for New Code for Neonatal Screening

- Currently physicians are using disease codes for positive screens.
- Therefore, surveillance data are skewed.
- A new code would accurately describe the clinical situation between positive screen and final diagnosis.
- This is analogous to 796.5, “Abnormal finding on antenatal screening.”

## New Code Recommendation for Neonatal Screening

- Position new code under 796:                 Other nonspecific abnormal findings
- 796.6 “Nonspecific abnormal findings on neonatal screening”                             		Excludes: nonspecific serologic evidence 	of HIV