Glycogenosis type IV is an autosomal recessive disease, exceptionally diagnosed at birth: only very few reports of the fatal perinatal neuromuscular form have been described. We report on two sibling male newborns who died
at 10 and 4 weeks of age with clinical signs of a systemic storage disease. Prenatal history included
polyhydramnios, reduced fetal movements and
fetal hydrops, and
Caesarean section was performed at 36 weeks of gestational age because of
fetal distress. At birth, both babies showed severe
hypotonia,
hyporeflexia and no spontaneous breathing activity. They never showed active movements, sucking and swallowing and were
respirator-dependent until death. A muscle biopsy revealed, in both patients, the presence of PAS-positive and partially
diastase-resistant cytoplasmic inclusions containing granular and filamentous
amylopectin-like material. This suggested that the stored material consisted of abnormal
glycogen. At autopsy, ultrastructural examination of cardiac and skeletal muscle, liver, kidney and brain showed PAS-positive
diastase-resistant eosinophilic cytoplasmic inclusions. Determination of
branching enzyme activity, in cultured fibroblasts from the second patient, showed markedly reduced
enzyme activity, confirming diagnosis of
glycogenosis type IV. Our patients showed the full spectrum of both prenatal signs (
hydrops,
polyhydramnios) and postnatal signs (
hypotonia,
hyporeflexia, absence of active movements,
cardiomegaly), which have been reported previously. They suffered from a very severe form of
glycogenosis type IV with clinical and histological involvement of many tissues and organs. Diagnosis was accomplished on the second baby and required several biochemical and histological studies, in order to rule out both neuromuscular disorders and the most common storage diseases with neonatal onset. In our experience, the correct interpretation of the histological findings was essential in the search for the diagnosis.