DOUBLE HOMOZYGOSITY FOR MUTATIONS OF AGL AND SCN9A MIMICKING NEUROHEPATOPATHY SYNDROME

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Congenital indifference to pain (CIP, MIM #243000) is rare (<30 cases reported). We describe a consanguineous family from Egypt with the index patient displaying lesions typical of CIP. In addition, he had short stature, myopathy, and liver dysfunction—a combination typical of Navajo neurohepatopathy (NNH, MIM #256810). No mutation was found in MPV17 , the gene primarily involved in NNH.1 Pain perception was normal in a sister with congenital liver disease. Detailed genetic and clinical investigation revealed two separate rare disorders in the index patient, glycogen storage disease type 3 (GSD III; MIM #232400) and CIP, based on homozygous mutations in the genes AGL and SCN9A . ### Case report. The index patient (IV-10, age 11 years) and his sister (IV-11, age 1 year 10 months) underwent detailed clinical assessment. Starting at 2 years of age, IV-10 developed frequent painless fractures of legs and arms, bruises, cuts, and abdominal enlargement. On recent examination, he had short stature (<3 SD), corneal ulcerations, self-mutilative injuries of lips, skin, and fingers, and limb deformities due to untreated fractures (figure). There was mild hypotonia in lower limbs, flexors of hips and trunk muscles, and hypesthesia in both arms. Liver enzymes (AST: 260 U/L, ALT: 607 U/L), creatine phosphokinase (CPK: 341 U/L), and serum triglycerides (214 mg%) were markedly elevated. Generalized decrease of bone density was noted (dual energy X-ray absorptiometry). Hepatosplenomegaly, hepatocyte swelling, and periportal fibrosis were consistent with GSD (ultrasonography, …