NEWBORN SCREEN AND CHALLENGES IN DIAGNOSIS OF LEAKY SCID AND CARTILAGE HAIR HYPOPLASIA

Abstract

Introduction Cartilage-hair hypoplasia (CHH) is a rare disorder of skeletal dysplasia with varying degrees of immunodeficiency. Diagnosis is clinical with affected individuals displaying disproportionately short limbs and fine sparse hair. Genetic analysis of the ribonuclease mitochondrial RNA processing gene (RMRP) is confirmatory. Case Description The patient is an ex-38-week male born to non-consanguineous parents of Mexican descent who is status post colostomy after failing to pass meconium due to Hirshprung Disease (HD). Newborn screen revealed TRECs of 1 and flow cytometry showed 446 CD3 cells with proportionally low naïve subset (180) and low recent thymic emigrants (110). Mitogen and CD3 stimulated lymphoproliferation were low normal. His SCID gene panel revealed a compound heterozygous mutation in the RMRP gene. Skeletal survey was unremarkable and he was non-dysmorphic. He was ultimately discharged home with climbing CD3 populations. At 6 months of age his CD3 count was 970 and he had protective vaccine titers to haemophilus influenza and tetanus after two doses of vaccines. Discussion This case represents a unique presentation of CHH given lack of skeletal dysplasia and classic hair findings. The diagnosis was not made clinically but rather by laboratory studies: initially with the results of the failed newborn screen and later by focused genetic testing. Importantly, this ribosomal defect is not found on whole exome sequencing. Unlike our patient, prior reports of CHH with HD describe severe immunodeficiency. In this case, reassessment and clinical vigilance are essential before moving forward with hematopoietic stem cell transplant. Cartilage-hair hypoplasia (CHH) is a rare disorder of skeletal dysplasia with varying degrees of immunodeficiency. Diagnosis is clinical with affected individuals displaying disproportionately short limbs and fine sparse hair. Genetic analysis of the ribonuclease mitochondrial RNA processing gene (RMRP) is confirmatory. The patient is an ex-38-week male born to non-consanguineous parents of Mexican descent who is status post colostomy after failing to pass meconium due to Hirshprung Disease (HD). Newborn screen revealed TRECs of 1 and flow cytometry showed 446 CD3 cells with proportionally low naïve subset (180) and low recent thymic emigrants (110). Mitogen and CD3 stimulated lymphoproliferation were low normal. His SCID gene panel revealed a compound heterozygous mutation in the RMRP gene. Skeletal survey was unremarkable and he was non-dysmorphic. He was ultimately discharged home with climbing CD3 populations. At 6 months of age his CD3 count was 970 and he had protective vaccine titers to haemophilus influenza and tetanus after two doses of vaccines. This case represents a unique presentation of CHH given lack of skeletal dysplasia and classic hair findings. The diagnosis was not made clinically but rather by laboratory studies: initially with the results of the failed newborn screen and later by focused genetic testing. Importantly, this ribosomal defect is not found on whole exome sequencing. Unlike our patient, prior reports of CHH with HD describe severe immunodeficiency. In this case, reassessment and clinical vigilance are essential before moving forward with hematopoietic stem cell transplant.