Kaplan + Sadock's Synopsis of Psychiatry, 11e

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31.3 Intellectual Disability

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-

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.

Table 31.3-3 Impairment in Disorders with Inborn Errors of Metabolism

Hereditary Transmission a

Prenatal Diagnosis

Intellectual Disability Clinical Signs

Disorder

Enzyme Defect

I. LIPID METABOLISM

 Niemann-Pick disease   Group A, infantile   Group B, adult   Groups C and D,    intermediate Infantile Gaucher’s disease

Unknown

Hepatomegaly

+ –

± +

A.R.

Sphingomyelinase

Hepatosplenomegaly Pulmonary infiltration

Unknown

b -Glucosidase

+

±

A.R.

Hepatosplenomegaly, pseudobulbar palsy Macular changes, seizures, spasticity Hepatosplenomegaly, bone changes

+

+

Tay-Sachs disease

A.R.

Hexosaminidase A

b -Galactosidase

+

+

Generalized gangliosidosis

A.R.

+

+

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

b -Galactosidase

+

Fabry’s disease

X.R.

–

Angiokeratomas, renal failure

II. MUCOPOLYSACCHARIDE METABOLISM Hurler’s syndrome MPS I A.R.

+ + +

+ + +

Iduronidase

? ?

Hurler’s disease II

X.R. A.R.

Iduronate sulfatase

Sanfilippo’s syndrome III

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

+

+

Hepatomegaly, bone changes, swollen gingivae

N -acetylglucosaminyl- phospho transferase

( continued )