Early-onset fetal hydrops and muscle degeneration in siblings due to a novel variant of type IV glycogenosis

Abstract

We report on 3 consecutive sib fetuses, presenting at 13, 12, and 13 weeks of gestation, respectively, with fetal hydrops, limb contractures, and akinesia. Autopsy of the first fetus showed subcutaneous fluid collections and severe degeneration of skeletal muscle. Histologic studies demonstrated massive accumulation of diastase-resistant periodic acid-Schiff-positive material in the skeletal muscle cells and epidermal keratinocytes of all 3 fetuses. Enzyme studies of fibroblasts from the 3rd fetus showed deficient activity of glycogen brancher enzyme, indicating that this is a new, severe form of glycogenosis type IV with onset in the early second trimester.

Neonatal type IV glycogen storage disease associated with “null” mutations in glycogen branching enzyme 1

“…GSD IV also has been shown to present as hydrops fetalis, associated with muscle degeneration and flexion contractures, in two unrelated patients diagnosed at 34 weeks' gestation. 20,21 Parental consanguinity was revealed in 3 of 9 families.…”

Early fetal akinesia deformation sequence: A case report with unusual autoptic features

“…The human phenotype of FADS is not specific, but represents an etiologically heterogenous deformation sequence that can result from a variety of congenital neuropathies [1][2][3][4][5], myopathies [6][7][8][9][10][11] and restrictive dermopathies [13,14]. Some features of FADS are due to decreased intrauterine fetal movements.…”

“…Thompson et al presented 11 new cases in 1987, confirming autosomal recessive inheritance and emphasizing that several patients had consanguineous parents and multiple cases were present in same families [15]. The cases of LMPS may be due to glycogenosis type IV [6] and type VII [9].…”

“…On ultra-structural examination of muscle tissue, accumulation of glycogen was observed within the sarcoplasm, as non-membrane bound cytoplasmic inclusions, composed of fine granular or short fibrillary material [6].…”

“…The FADS, in fact, can be attributed to various conditions, including disorders of the central nervous system [1][2][3][4][5], diseases of muscles [6][7][8][9][10][11], connective tissue disorders [12] and dermopathy [13,14]. Clinical manifestations of FADS include: intrauterine growth restriction (IUGR), cranio-facial anomalies, limb anomalies, pulmonary hypoplasia, short umbilical cord, polyhydramnios and abnormal dermatoglyphics.…”