Category Specific Type Enzyme Deficiency Morphologic Changes Clinical Features

Hepatic Type Hepatorenal—von

Gierke disease (type I)

Glucose-6-phosphatase Hepatomegaly—intracytoplasmic

accumulations of glycogen and small

amounts of lipid; intranuclear glycogen

In untreated patients: failure to thrive, stunted growth,

hepatomegaly, and renomegaly. Hypoglycemia due to

failure of glucose mobilization, often leading to

convulsions. Hyperlipidemia and hyperuricemia resulting

from deranged glucose metabolism; many patients develop

gout and skin xanthomas. Bleeding tendency due to

platelet dysfunction. With treatment most survive and

develop late complications, e.g., hepatic adenomas

Renomegaly—intracytoplasmic

accumulations of glycogen in cortical

tubular epithelial cells

Myopathic Type McArdle syndrome (type

V)

Muscle phosphorylase Skeletal muscle only—accumulations of

glycogen predominant in subsarcolemmal

location

Painful cramps associated with strenuous exercise.

Myoglobinuria occurs in 50% of cases. Onset in adulthood

(>20 years). Muscular exercise fails to raise lactate level in

venous blood. Serum creatine kinase always elevated.

Compatible with normal longevity

Miscellaneous Types Generalized glycogenosis

—Pompe disease (type II)

Lysosomal glucosidase

(acid maltase)

Mild hepatomegaly—ballooning of

lysosomes with glycogen, creating lacy

cytoplasmic pattern

Massive cardiomegaly, muscle hypotonia, and

cardiorespiratory failure within 2 years. A milder adult

form with only skeletal muscle involvement, presenting

Cardiomegaly—glycogen within with chronic myopathy

sarcoplasm as well as membrane-bound

Skeletal muscle—similar to changes in

heart

the urine if allowed to stand and undergo oxidation.[38] The gene encoding homogentisic oxidase, mapped to 3q21, was cloned in 1996,[39] 64 years after the initial description of the disease

by Garrod.

Morphology.

The retained homogentisic acid selectively binds to collagen in connective tissues, tendons, and cartilage, imparting to these tissues a blue-black pigmentation (ochronosis)most evident in

the ears, nose, and cheeks. The most serious consequences of ochronosis, however, stem from deposits of the pigment in the articular cartilages of the joints.In some obscure manner,

the pigmentation causes the cartilage to lose its normal resiliency and become brittle and fibrillated.[40] Wear-and-tear erosion of this abnormal cartilage leads to denudation of the

subchondral bone, and often tiny fragments of the fibrillated cartilage are driven into the underlying bone, worsening the damage. The vertebral column, particularly the intervertebral disc, is

the prime site of attack, but later the knees, shoulders, and hips may be affected. The small joints of the hands and feet are usually spared.

The metabolic defect is present from birth, but the degenerative arthropathy develops slowly and usually does not become clinically evident until the thirties. Although it is not lifethreatening,

it may be severely crippling. The disability may be as extreme as that encountered in the severe forms of osteoarthritis ( Chapter 26 ) of the elderly, but in alkaptonuria the

arthropathy occurs at a much earlier age.

Date: 2016-04-22; view: 683