Lysosomal storage disorders in the newborn

Abstract

Lysosomal storage disorders are rare inborn errors of metabolism, with a combined incidence of 1 in 1500 to 7000 live births. These relatively rare disorders are seldom considered when evaluating a sick newborn. A significant number of the >50 different lysosomal storage disorders, however, do manifest in the neonatal period and should be part of the differential diagnosis of several perinatal phenotypes. We review the earliest clinical features, diagnostic tests, and treatment options for lysosomal storage disorders that can present in the newborn. Although many of the lysosomal storage disorders are characterized by a range in phenotypes, the focus of this review is on the specific symptoms and clinical findings that present in the perinatal period, including neurologic, respiratory, endocrine, and cardiovascular manifestations, dysmorphic features, hepatosplenomegaly, skin or ocular involvement, and hydrops fetalis/congenital ascites. A greater awareness of these features may help to reduce misdiagnosis and promote the early detection of lysosomal storage disorders. Implementing therapy at the earliest stage possible is crucial for several of the lysosomal storage disorders; hence, an early appreciation of these disorders by physicians who treat newborns is essential.

FIGURE 1

Algorithm of the clinical evaluation recommended for an infant with a suspected LSD. GAGs indicates glycosaminoglycans.

FIGURE 2

Clinical photographs. A, Coarse facial features in a patient with I-cell disease. B, Skeletal survey showing lytic bony lesions in a patient with I-cell disease. C, Gum hyperplasia in a patient with I-cell disease. D, A newborn with perinatal-lethal type 2 Gaucher disease presenting with contractures and hepatosplenomegaly.

FIGURE 3

Algorithm for the clinical evaluation of a fetus or newborn with NIHF. IEM indicates inborn errors of metabolism; NPC, Niemann-Pick disease type C.