Acid Maltase Deficiency Myopathy Clinical Presentation

Several forms of acid maltase deficiency (AMD) have been observed. Clinical variation between siblings is uncommon; however, the occurrence of infantile or juvenile forms and adult forms in the same family has been reported, probably owing to various compound heterozygous states. ^[14]

Glycogenoses include the following:

• Type I - von Gierke disease (glucose-6-phosphatase deficiency)

• Type II - Pompe disease (acid maltase deficiency) ^{[2, 3, 4]}

• Type III - Forbes disease (debrancher, amylo-1,6-glucosidase deficiency)

• Type IV - Andersen disease (brancher, amylo-transglucosidase deficiency)

• Type V - McArdle disease (myophosphorylase deficiency)

• Type VI - Hers disease (hepatophosphorylase deficiency)

• Type VII - Tarui disease (phosphofructokinase deficiency)

Other glycogenoses include the following:

• Smith disease (acid maltase deficiency) (late infantile form)

• Engel disease (acid maltase deficiency) (adult form)

• Hers disease (hepatophosphorylase deficiency)

• Hug disease (hepatic phosphorylase kinase deficiency)

• Satoyoshi disease (phosphohexose isomerase deficiency)

• Thomson disease (phosphoglucomutase deficiency)

• Glycogen synthase deficiency

• Bresolin disease (phosphoglycerate kinase deficiency)

• Tonin disease (phosphoglycerate mutase deficiency)

• Tsujimo disease (lactate dehydrogenase deficiency)

Infantile form of AMD

Pompe disease is characterized by hypotonia, weakness, areflexia, macroglossia, massive cardiomegaly, and moderate hepatomegaly. Development usually is normal for the first weeks or months of life, but as the disease progresses, spontaneous movements slowly decline and the infant's cry becomes weak and struggling. Swallowing becomes difficult. Skeletal muscle weakness and inability to handle pooled secretions lead to respiratory difficulty. Pulmonary atelectasis may be seen. Cardiomegaly then results, and a soft murmur sometimes is heard over the left sternal border. Ultimately, hepatomegaly appears, and the tongue may become enlarged and may protrude awkwardly. Skeletal muscles are small and firm, and the stretch reflexes are depressed. A sharp contrast can be seen between the gross motor dysfunction and the normal mental development. ^{[2, 3, 4]}

Although the liver becomes progressively enlarged, neither hypoglycemia nor ketosis is noted, and the mobilization of glycogen by glucagon or epinephrine is normal. Death typically occurs as a result of heart failure within the first 2 years of life. When cardiac involvement is less severe, survival can extend beyond 2 years, depending on the degree of muscular and neurologic function.

Late infantile form of AMD

Difficulty walking usually is the first symptom to appear in the late infantile form of AMD. The signs and symptoms may simulate those of Duchenne muscular dystrophy but usually manifest during the first few months of life. In such patients, the gastrocnemius and deltoid muscles are firm and rubbery. Hypertrophy of the calf muscles is noted, and the Gowers sign often is present. Toe walking develops with ankle contractures. Ambulation is unsteady and wobbly because of lumbar lordosis. The disease can progress for several years until death results from cardiorespiratory decompensation.

Juvenile and adult forms of AMD

Motor delay and progressive myopathy are the main features of the juvenile and adult forms of AMD. The disease is limited to skeletal muscle and leads to progressive weakness and respiratory insufficiency. ^{[5, 6, 7, 8, 9, 15]} Mental retardation may be present. Calf enlargement may be observed, and the Gowers sign may be present. Muscle creatine kinase (CK) may range from 200-2000 IU/L, but CK usually is within the reference range in the adult form. Distinct electromyogram (EMG) findings usually can be found. Because enzymatic function is not entirely affected in the juvenile and adult forms, cardiac function in these groups usually is normal.

Patients with the adult form may have no complaints until the second or third decade of life. Progressive weakness occurs into the sixth decade of life. The legs are affected more than the arms, with proximal muscles involved earlier than distal ones, and the pelvic girdle is more involved than the shoulder. Hepatomegaly and cardiomegaly usually are not seen; however, these conditions are sometimes seen in the terminal phase. This form of the disease may be confused with limb-girdle dystrophy or chronic polymyositis. The heart, liver, and CNS generally are uninvolved in the juvenile and adult forms of AMD.

A study by Jones et al indicated that tongue characteristics may aid in differentiating late-onset AMD from other myopathies. Compared with patients suffering from other myopathies, acquired or hereditary, the tongues of those with late-onset AMD were weaker and had reduced muscle thickness, with ultrasonographic results suggesting fibrofatty replacement and atrophy. ^[16]

Manifestations of AMD

See the list below:

• Infantile AMD

  • Early hypotonia

  • Massive cardiomegaly, soft murmur, and heart failure

  • Weakness and depressed or absent muscle stretch reflexes

  • Macroglossia

  • Moderate hepatomegaly

  • Mental retardation

  • "Metabolic" anterior horn cell pathology (uncommon)

• Juvenile ^{[5, 6, 7, 8, 9]}

  • Motor delay

  • Progressive myopathy

  • Signs and symptoms limited to skeletal muscles

  • Respiratory insufficiency

• Adult ^{[5, 6, 7, 8, 9]}

  • Onset occurs in the second or third decade of life. Muscle weakness progresses in the third to sixth decades of life.

  • Proximal muscle weakness is greater than distal muscle weakness.

  • The pelvic girdle is more involved than the shoulder. Intercostal and diaphragmatic involvement is common.

  • No liver, heart, or tongue enlargement occurs, except sometimes in terminal stages.

Acid maltase deficiency is an inherited, autosomal condition characterized by a buildup of glycogen in the cells.