Page 254 - Color Atlas Of Pathophysiology (S Silbernagl Et Al, Thieme 2000)

Carbohydratis abnormal type of glycogen is stored in the brain,
heart, muscle, and liver. In type VII (Tauri; muscle
Abnormalities of carbohydrate metabolism are phosphofructokinase deficiency), on the other hand,
usually caused by enzymopathies or abnormal glucose is prevented from being utilized to provide
the muscles with energy.
regulation (see also anemia, → p. 30ff. or dia-
betes mellitus, → p. 286ff.). Depending on the primary effects of the en-
In galactosemia (→ p. 243 C) galactose is zyme deficiencies, one can simplify the classifi-
split off fromlactose in the gut and can be chan- cationbydividingtheglycogenstoragediseases
ged into glucose or glycogen, especially in the intolivertypes(I,III,VI,VIII),muscletypes(V,VII),
liver. In case of a galactose-1-uridyl transferase and other types (II, IV) (→ B). In the liver types
deficiency (→ p. 243 C1), galactose-1-phos- hepatomegaly (due to excess deposition of gly-
phateaccumulates in many organs with the on- cogen)andhypoglycemiaaretheprominentfea-
set of breast-feeding. The organs are damaged tures, while in the muscle types it is largely en-
as galactose-1-phosphate inhibits enzymes ergy deficiency. Physical work does not increase
which are active in glucose metabolism. Dam- plasma lactate and leads to rapid fatigue, mus-
age can also be caused by galactitol, formed cle cramps and muscle pain as well as to myo-
from galactose-1-phosphate. Early diagnosis globinuria (in type V), which may cause renal
failure. The effects of type II (cardiomegaly,
and a galactose-freediet canpreventsuch dam-
Metabolism age (uridine diphosphate galactose can still be weakness of respiratory muscles) and type IV
(liver failure) often end in death in childhood.
formed). A galactokinase deficiency (→ p. 243
C2) associated with hypergalactosemia and
In hereditary fructose intolerance (→ A,
8 hypergalactosuria is less serious. Lipidoses
Lipidoses are disorders of fat metabolism, in
center) there is a defect of fructose-1-phos- which defects of enzymes and other proteins
phate aldolase. The breakdown of fructose cause the accumulation (and thus deposition)
(fruits, saccharose) is blocked and fructose-1- of lipids.
phosphate accumulates. This inhibits phos-
phorylase and fructose-1,6-diphosphate aldo- In Gaucher’s disease there is a lysosomal β-glucocer-
lase in the liver, thus causing hepatogenic hy- ebrosidase (β-glucosidase) deficiency, in which glu-
cocerebroside accumulates (adult form) in the
poglycemia, acute liver failure, or cirrhosis spleen, liver, lung, and bone marrow (Gaucher cells),
(→ p.172ff.). If diagnosed early and the patient hypersplenism (thrombocytopenia), spontaneous
put on a fructose-free diet, life expectancy is fractures as well as pneumonia and cor pulmonale
normal, while fructose infusion can quickly be being some of the consequences. In Niemann–Pick
fatal due to liver failure. disease (five phenotypes, A–E) there is an accumula-
Glycogen storage diseases. Glucose is tion of sphingomyelin and cholesterol in the lyso-
somes. In types A (80% of all cases of the disease)
stored in muscles and liver as glycogen. Break- and B there is a deficiency of sphingomyelinase,
ing it down provides glucose that is used local- while in type C1 the deficiency is of a protein
ly or reaches other organs (→ A,B). If the (NPC1) which plays an important role in the intracel-
breakdown of glycogen is blocked, glycogen lular distribution of cholesterol. The effects of type A
overloading and hypoglycemia result. This is are enlargement of several organs and severe neuro-
caused by enzyme deficiencies. logical abnormalities that can be fatal already in
childhood. A deficiency of acid lipase is the cause of
Several types are distinguished (→ A): type Ia (von cholesterol-ester storage disease (liver cirrhosis and
Gierke; glucose-6-phosphatase deficiency); type Ib atherosclerosis) and in Wolman’s disease (the infan-
(deficiency of microsomal glucose-6-phosphate tile form of acid lipase deficiency). The gangliosido-
translocase [not shown in diagram]); type II (Pompe; ses (e.g., Tay–Sachs and Sandhoff’s disease) are
lysosomal α-glucosidase deficiency); type III (Forbes, caused by various defects of the hexosaminidases
Cori; debrancher enzyme deficiency, the most com- and their activators, or of β-galactosidase. In most
mon type); type V (McArdle; muscle phosphorylase forms the accumulated gangliosides lead to very se-
deficiency); type VI (Hers; hepatic phosphorylase de- vere cerebral disorders and death in early childhood.
ficiency); and type VIII (Huijing; hepatic phosphory- In Refsum’s disease the breakdown of phytanic acid
lase b kinase deficiency). A (very rare) deficiency of is blocked (defect of phytanic acid-α-hydroxylase),
244 glycogen synthesis (type IV; Andersen; brancher en- as a result of which it accumulates and, incorporated
zyme deficiency) results in glycogenosis because an into myelin, leads to polyneuropathy.
Silbernagl/Lang, Color Atlas of Pathophysiology © 2000 Thieme
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