Background:The human dolichol-phosphate-mannose (DPM) synthase is a heterotrimeric complex composed of DPM1, DPM2 and DPM3. Only mutations in DPM1 (the catalytic subunit) and more recently in DPM3 have been described. Case Report: The girl was born to unrelated parents at the 32th week of gestation complicated by polyhydramnios. At birth she had normal growth parameters, severe hypotonia and dysmorphism. At six months, microcephaly (OFC: 33.5 cm), keel thorax,widely spaced nipples and joint flexion contractures were seen. Repeated laboratory investigations showed elevation of serum transaminases and CPK levels and coagulopathy. At age 20 months there were severe hypotonia, no head control, reduced active limb movements with normal osteotendineous reflexes. She experienced pharmacoresistant generalized tonic seizures and myoclonic jerks. Funduscopy showed optic atrophy. Brain MRI documented loss of cerebral white matter, without cerebellar atrophy. She died at age 36 months from pneumonia. Serum Transferrin (Tf) IEF showed overt increase of disialo-Tf and a very faint asialo-Tf band (type I pattern). PMM and PMI enzymes were normal. MALDI-MS of serum Tf showed di-glycosylated Tf and an additional glycoform owing to mono-glycosylated Tf. Unlike CDG-Ia (PMM deficiency), no a-glycosylated Tf species were detectable. Lipid-linked oligosaccharides analyses showed an accumulation of dol-PP-GlcNAc2-Man5. No mutations in DPM1, ALG3 or MPDU1 were detected. The patient was compound heterozygote for a splice mutation (c.4-1G>C) and a missense mutation (c.68A>G, p.Y23C) in the DPM2 gene. Conclusions: Prominent neurological involvement, dysmorphism and fatal outcome were hallmark clinical features in the first CDG patient with DPM2 mutation.
Clinical characterization of a novel congenital disorder of glycosylation (DPM2 mutation)
2010
Abstract
Background:The human dolichol-phosphate-mannose (DPM) synthase is a heterotrimeric complex composed of DPM1, DPM2 and DPM3. Only mutations in DPM1 (the catalytic subunit) and more recently in DPM3 have been described. Case Report: The girl was born to unrelated parents at the 32th week of gestation complicated by polyhydramnios. At birth she had normal growth parameters, severe hypotonia and dysmorphism. At six months, microcephaly (OFC: 33.5 cm), keel thorax,widely spaced nipples and joint flexion contractures were seen. Repeated laboratory investigations showed elevation of serum transaminases and CPK levels and coagulopathy. At age 20 months there were severe hypotonia, no head control, reduced active limb movements with normal osteotendineous reflexes. She experienced pharmacoresistant generalized tonic seizures and myoclonic jerks. Funduscopy showed optic atrophy. Brain MRI documented loss of cerebral white matter, without cerebellar atrophy. She died at age 36 months from pneumonia. Serum Transferrin (Tf) IEF showed overt increase of disialo-Tf and a very faint asialo-Tf band (type I pattern). PMM and PMI enzymes were normal. MALDI-MS of serum Tf showed di-glycosylated Tf and an additional glycoform owing to mono-glycosylated Tf. Unlike CDG-Ia (PMM deficiency), no a-glycosylated Tf species were detectable. Lipid-linked oligosaccharides analyses showed an accumulation of dol-PP-GlcNAc2-Man5. No mutations in DPM1, ALG3 or MPDU1 were detected. The patient was compound heterozygote for a splice mutation (c.4-1G>C) and a missense mutation (c.68A>G, p.Y23C) in the DPM2 gene. Conclusions: Prominent neurological involvement, dysmorphism and fatal outcome were hallmark clinical features in the first CDG patient with DPM2 mutation.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
