1 Área da Mulher, Criança e Adolescente, Hospital Dona Estefânia, Centro Hospitalar Universitário de Lisboa Central, Lisboa, Portugal
2 Unidade de Cuidados Intensivos Neonatais da Maternidade Dr. Alfredo da Costa, Área da Mulher, Criança e Adolescente, Centro Hospitalar Universitário de Lisboa Central, Lisboa, Portugal
3 Unidade de Reumatologia Pediátrica, Área da Mulher, Criança e Adolescente, Hospital Dona Estefânia, Centro Hospitalar Universitário de Lisboa Central, Lisboa, Portugal
4 Centro de Referência de Doenças Hereditárias do Metabolismo, Centro Hospitalar Universitário de Lisboa Central, Lisboa, Portugal
5 Unidade de Imunodeficiências Primárias, Área da Mulher, Criança e Adolescente, Hospital Dona Estefânia, Centro Hospitalar Universitário de Lisboa Central, Lisboa, Portugal
- Poster -15th International Symposium of Sociedade Portuguea de Doenças Metabólicas
- Coimbra, 14 a 16 março de 2019
Background: Mevalonate kinase deficiency (MKD) is recessively inherited inborn error of isoprene biosynthesis with a wide spectrum of manifestations. Mevalonic aciduria (MA) represents the most severe end of the MKD spectrum and characteristically presents in the first few months of life, with antenatal presentations linked with a high rate of stillbirth in affected families. MA is characterized by recurrent attacks of fever, developmental delay, ataxia, dysmorphic features, failure to thrive, cataracts, and retinal dystrophy. The prognosis of MA is poor, as the central nervous system involvement is progressive and independent of inflammatory control.
Case Report: Newborn male, first child of non-consanguineous parents, born at 29 weeks by cesarian section for preclampsia, requiring advanced reanimation procedures and invasive ventilation. Pre-natal echography at 28 weeks showed fetal hydrops and indirect findings of anaemia needing intrauterine transfusion. The mother had a previous miscarriage at 21 weeks with fetal hydrops and dysmorphic features. At initial observation the baby had hepatosplenomegaly, ascites, hypoplasia of abdominal rectus, cholestatic liver disease, anemia and thrombocytopenia. Extensive investigation of non-immune hydrops foetalis at this time excluded mucopolysaccharidoses, oligosaccharidoses, sphingolipidoses and Niemann Pick type C. Criteria for hemophagocitic lymphohistiocytosis (HLH) were met with bicytopenia, splenomegaly, hypertriglyceridemia, hyperferritinemia and elevation of CD25. Primary HLH was excluded (normal degranulation, normal cytotoxicity) and secondary HLH was admitted in the context of an autoinflammatory disease, as the clinical condition evolved to recurring bouts of fever, urticariform rash, arthritis and enthesitis of the small joints. A therapeutic trial with interleukin-1 receptor antagonist (anakinra) lead to normalization of inflammatory parameters and disappearance of rash and arthritis. Genetic study found two compound heterozygous variants in the MVK gene (p.L297I and p.A214K), not reported in literature but probably pathogenic. Marked elevation of mevalonic acid in urine confirmed the diagnosis of MKD. The baby was discharged after 6 months, with controlled outbreaks (on 6 mg/kg of canakinumab every 3 weeks) but with signs of neurological impairment like hypotonia and oculomotor apraxia. He is currently waiting hematopoietic stem cell trasnplantation
Comments: The inicial constellation of hepatosplenomegaly, cholestatic liver disease, anemia, and thrombocitopenia in a newborn prompt the investigation of lysosomal storage diseases and Niemann-Pick Type C but further clinical evolution lead to diagnosis of MA and prompt treatment. Heterogeneous presentations stress the importance of multidisciplinary approach.