Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (417 page)

   Mutations in the gene for ferroportin cause autosomal dominant HH.

   Mutations in the genes for transferring and ceruloplasmin produce autosomal recessive disorders of iron overload.

   Limitations

   Serum ferritin may be increased in severe inflammatory conditions and in hepatic necrosis, in the absence of IOD. In HH patients, it becomes elevated later in life than transferrin saturation.

   Serum iron levels fluctuate diurnally, with lowest values in the evening and highest between 7
AM
and noon.

Suggested Readings

Adams PC, Barton JC. How I treat hemochromatosis.
Blood.
2010;116:317–325.

Camaschella C. Treating iron overload.
N Engl J Med.
2013;368:2325–2327.

Fleming RE, Ponka P. Iron overload in human disease.
N Engl J Med.
2012; 366:348–359.

Hoffbrand AV, Taher A, Cappelini MD. How I treat transfusional hemochromatosis.
Blood.
2012;120:3657–3669.

*
Co-authored by Patricia Minehart Miron, PhD & Hongbo Yu, MD, PhD.

^†
French-American-British classification, as previously used, was based on morphologic criteria.

‡
Co-authored by Patricia Minehart Miron, PhD & Hongbo Yu, MD, PhD.

**
Co-authored by Patricia Miron, PhD

^††
Atypical CML is referred by some hematologists to cases mimicking CML, but without evidence of BCR-ABL gene fusion. These cases are classified by WHO in the group of myeloproliferative/myelodysplastic disorders. Another variant is the rare chronic neutrophilic leukemia, characterized by mature granulocytic hyperplasia and elevated LAP, but absent Philadelphia chromosome.

^‡‡
Co-authored by Patricia Minehart Miron, PhD & Hongbo Yu, MD, PhD.

^§§
Co-authored by Patricia Minehart Miron, PhD.

***
Quinine is present in certain soft drinks.

^†††
It may be advantageous to order together the five first-tier tests, because inherited venous thrombophilia cases are often due to a polygenic effect.

^‡‡
Warfarin therapy reduces vitamin K–dependent factors including proteins C, S, and Z and will result in spuriously low values in these patients. Testing for protein Z is not recommended at this time.

^§§§
There is no documented indication to order the tests suggested for venous thrombophilia in cases of arterial thrombophilia (except for APCR in pediatric thrombophilia with idiopathic ischemic stroke).

Chapter 10

Hereditary and Genetic Diseases

Marzena M. Galdzicka, Patricia Minehart Miron and Edward I. Ginns

Overview

Molecular Diagnosis: Types of Genetic Testing

Genetic Counseling

Informed Consent

Factors to Consider When Ordering Genetic Tests

Genetic Nondiscrimination Legislature

Molecular Tests Used for Detection and Monitoring Infectious Diseases

Disorders of the Immune System

Familial Mediterranean Fever (FMF)

Metabolic Disorders

Familial Hyperinsulinism (FHI)

Maple Syrup Urine Disease (MSUD)

Phenylketonuria (Folling Disease; PKU)

Lysosomal Storage Disorders

Canavan Disease

Cystinosis (Cystinosis, Nephropathic; CTNS)

Fabry Disease (Angiokeratoma Corporis Diffusum, Anderson-Fabry Disease)

Farber Disease (Farber Lipogranulomatosis; Acid Ceramidase Deficiency)

Gaucher Disease (Acid Beta- Glucosidase Deficiency; GBA Deficiency)

Glycogen Storage Disease, Type I (Glucose-6-Phosphatase Deficiency, von Gierke Disease)

Glycogen Storage Disease, Type II (Pompe Disease; Acid Alpha-Glucosidase Deficiency; Acid Maltase Deficiency)

GM
1
Gangliosidosis (Landing Disease, Systemic Late Infantile Lipidosis, Beta-Galactosidase-1 Deficiency)

Hunter Syndrome (Mucopolysaccharidosis II; Iduronate-2-Sulfatase Deficiency)

Hurler Syndrome (Mucopolysaccharidosis 1H, MPS1-H)

I-Cell Disease (Mucolipidosis II)

Krabbe Disease (Globoid Cell Leukodystrophy; Galactocerebrosidase Deficiency)

Maroteaux-Lamy Syndrome (Arylsulfatase B Deficiency; Mucopolysaccharidosis VI)

Metachromatic Leukodystrophy (Arylsulfatase A Deficiency)

Morquio Syndrome (Mucopolysaccharidosis IVA GALNS Deficiency)

Mucolipidosis III (
N
-Acetylglucosamine-1-Phosphate Transferase Deficiency, Pseudo-Hurler Dystrophy)

Niemann-Pick Disease, Types A and B (Sphingomyelinase Deficiency)

Niemann-Pick Disease, Type C (Niemann-Pick Disease With Cholesterol Esterification Block)

Sanfilippo Type A Syndrome (Heparan Sulfatase Deficiency; Mucopolysaccharidosis IIIA)

Tay-Sachs Disease (GM
2
Gangliosidosis, Type I; Hexosaminidase A Deficiency)

Wolman Disease (Cholesteryl Ester Storage Disease, Lal Deficiency, Cholesteryl Ester Hydrolase Deficiency)

Peroxisomal Disorders

Adrenoleukodystrophy (ALD)

Batten Disease (CLN3, Batten-Spielmeyer-Vogt Disease, Neuronal Ceroid Lipofuscinosis)

Neurologic Disorders

Alzheimer Disease (Presenile and Senile Dementia)

Angelman Syndrome (AS)

Familial Dysautonomia

Fragile X Syndrome of Mental Retardation/FMR1-Related Disorders

Huntington Disease

Lesch-Nyhan Syndrome

Menkes Syndrome (Kinky Hair)

Parkinson’s Disease (PD)

Prader-Willi Syndrome (PWS)

Rett Syndrome

Spinal Cerebellar Ataxias

Wilson Disease (Hepatolenticular Degeneration)

Neuromuscular Disorders

Amyotrophic Lateral Sclerosis (ALS; Lou Gehrig Disease)

Charcot Marie Tooth Hereditary Neuropathy (CMT)

Muscular Dystrophy, Duchenne Type; DMD

Muscular Dystrophy, Becker Type; BMD

Myotonic Dystrophy Type 1

Friedreich Ataxia (FRDA)