31.3 Intellectual Disability
1125
seizures, disturbances in gait, and mild intellectual impair-
ment. Abnormal pigmentation reflecting adrenal insufficiency
sometimes precedes the neurological symptoms, and attacks
of crying are common. Spastic contractures, ataxia, and swal-
lowing disturbances are also frequent. Although the course is
often rapidly progressive, some patients may have a relapsing
and remitting course.
Maple Syrup Urine Disease.
The clinical symptoms
of maple syrup urine disease appear during the first week of
life. The infant deteriorates rapidly and has decerebrate rigid-
ity, seizures, respiratory irregularity, and hypoglycemia. If
untreated, maple syrup urine disease is usually fatal in the first
months of life, and the survivors have severe intellectual dis-
Table 31.3-3
Impairment in Disorders with Inborn Errors of Metabolism
Disorder
Hereditary
Transmission
a
Enzyme Defect
Prenatal
Diagnosis
Intellectual
Disability Clinical Signs
I. LIPID METABOLISM
Niemann-Pick disease
Group A, infantile
Unknown
Hepatomegaly
Group B, adult
A.R.
Sphingomyelinase
+
±
Hepatosplenomegaly
Groups C and D,
intermediate
Unknown
–
+
Pulmonary infiltration
Infantile Gaucher’s disease
A.R.
b
-Glucosidase
+
±
Hepatosplenomegaly,
pseudobulbar palsy
Tay-Sachs disease
A.R.
Hexosaminidase A
+
+
Macular changes,
seizures, spasticity
Generalized gangliosidosis
A.R.
b
-Galactosidase
+
+
Hepatosplenomegaly,
bone changes
Krabbe’s disease
A.R.
Galactocerebroside
+
+
Stiffness, seizures
b
-Galactosidase
Metachromatic
leukodystrophy
A.R.
Cerebroside sulfatase
+
+
Stiffness,
developmental
failure
Wolman’s disease
A.R.
Acid lipase
+
–
Hepatosplenomegaly,
adrenal calcification,
vomiting, diarrhea
Farber’s lipogranulomatosis
A.R.
Acid ceramidase
+
+
Hoarseness,
arthropathy,
subcutaneous
nodules
Fabry’s disease
X.R.
b
-Galactosidase
+
–
Angiokeratomas, renal
failure
II. MUCOPOLYSACCHARIDE METABOLISM
Hurler’s syndrome MPS I
A.R.
Iduronidase
+
+
?
Hurler’s disease II
X.R.
Iduronate sulfatase
+
+
?
Sanfilippo’s syndrome III
A.R.
Various sulfatases (types
A–D)
+
+
Varying degrees of
bone changes,
hepatosplenomegaly,
joint restriction, etc.
Morquio’s disease IV
A.R.
N
-Acetylgalactosamine-6-
sulfate sulfatase
+
–
?
Maroteaux-Lamy
syndrome VI
A.R.
Arylsulfatase B
+
±
?
III. OLIGOSACCHARIDE AND GLYCOPROTEIN METABOLISM
I-cell disease
A.R.
Glycoprotein
N
-acetylglucosaminyl-
phospho transferase
+
+
Hepatomegaly, bone
changes, swollen
gingivae
ability. Some variants have been reported with transient ataxia
and only mild intellectual disability. Treatment follows the
general principles established for PKU and consists of a diet
very low in the three involved amino acids—leucine, isoleu-
cine, and valine.
Other Enzyme Deficiency Disorders.
Several enzyme
deficiency disorders associated with intellectual disability have
been identified, and still more diseases are being added as new
discoveries are made, including Hartnup disease, galactosemia,
and glycogen-storage disease. Table 31.3-3 lists 30 important
disorders with inborn errors of metabolism, hereditary trans-
mission patterns, defective enzymes, clinical signs, and relation
to intellectual disability.
(
continued
)
