G.P.315: Cases of normal to mildly elevated creatine kinase in muscle-eye-brain disease patients and delay in diagnosis

Abstract

The dystroglycanopathies are a genetically heterogeneous group of autosomal recessive muscular dystrophies that have in common abnormal glycosylation of alpha-dystroglycan. The spectrum of clinical features is wide and includes muscle-eye-brain disease (MEB), which typically encompass congenital muscular dystrophy, cobblestone lissencephaly and eye abnormalities. Serum creatine kinase (CK) is often elevated greater than fivefold. We describe three cases of MEB in whom the combination of low or normal serum CK and predominant upper motor neurone features led to delayed diagnosis. Case 1: 4-year-old boy presented antenatally with ventriculomegaly. MRI revealed cobblestone lissencephaly and cerebellar polymicrogyria. He was myopic. CK was 173 IU/L at 4 days. He appeared to have an evolving CP with central hypotonia, limb spasticity. His CK was 563 IU/L and compound heterozygous mutations in POMGnT1, c.511C>T and c.1895+1G>T was found at 2 years. Case 2: 4-year-old girl presented at 5 days with hypotonia. CK was 228 IU/L at 2 weeks and 248 IU/L by 3 months. MRI showed lissencephaly and widespread polymicrogyria with cerebellar cysts. She was myopic. She is bottom shuffling with preserved strength but evolving CP-like picture. At 2 years compound heterozygous mutations in POMGnT1, c.385C>T and c.1460delG were found. Case 3: 14 year-old male presented at 3 months with myopia. MRI was consistent with a neuronal migration defect. CK was 386 IU/L at 11 months. Presentation was that of an evolving motor disorder. He was diagnosed age 8 with a compound heterozygous mutations in LARGE. These cases highlight that patients with dystroglycanopathies with POMGnT1 and LARGE mutations can have normal or only mildly elevated CK levels, even beyond the first 6 months. The presentation suggests CP with preservation of muscle strength. It is important to suspect dystroglycanopathies with typical MRI changes and eye involvement, even in the light of normal CK without weakness.