Tricho-hepato-enteric syndrome: Further delineation of a distinct syndrome with neonatal hemochromatosis phenotype, intractable diarrhea, and hair anomalies

Abstract

We report on two sibs with syndromal congenital iron storage disease. Prenatal symptoms were IUGR, hydramnios, and placental hyperplasia. Clinical anomalies included hypertelorism and sparse, thin, curly hair (trichomalacia). Clinical course was marked by intractable diarrhoea, with normal histological and enzymological studies, cholestatic jaundice, hepatomegaly appearing after 30 days, and progressive liver failure, leading to death after a few months. The only metabolic anomaly was progressive hypermethioninemia. Pathologic examination of both children showed a similar pattern of multivisceral iron deposit compatible with a diagnosis of neonatal hemochromatosis: extensive liver fibrosis or cirrhosis with nodular regeneration, cholestasis, ductular proliferation, and hepatic, pituitary, thyroidal, adrenal, and pancreatic iron deposition. The unusual course for neonatal hemochromatosis in both sibs combined with concordant extrahepatic anomalies suggest that they could have a specific iron storage syndrome with possible autosomal recessive inheritance, probably similar to the sibship reported by Stanckler et al. [Arch Dis Child, 57:212-216, 1982].

Neonatal Hemochromatosis

“…Occasionally, the NH phenotype can arise from non-GALD diseases including perinatal infection, 3,24,25 trisomy 21, 14,26À28 mitochondrial DNA depletion due to deoxyguanosine kinase deficiency (DGUOK gene mutations), [29][30][31] bile acid synthetic defect delta 4-3-oxosteroid 5 beta-reductase deficiency (SRD5B1 mutations), [32][33][34] GRACILE syndrome (BCS1L mutation), 35,36 myofibromatosis, 14 tricho-hepato-enteric syndrome 37,38 and Martinez-Frias syndrome. 39 In cases of trisomy 21, transient megakaryocytic leukemia may explain the NH phenotype.…”

An infant with trichohepato-enteric syndrome: case report

“…1 44 cases have been published between 1982 and 2012. Literature reviewed showed that 9 clinical signs are associated with THE-S. [2][3][4][5][6][7][8][9][10][11][12][13][14][15] Three are constant: intractable diarrhea, facial dysmorphism and hair abnormality. Two are very frequent (more than 90%): IUGR and immunodeficiency; 2 are frequent: skin abnormalities and liver disease and 2 are rare: congenital cardiac defects and platelet anomaly.…”

“…Two are very frequent (more than 90%): IUGR and immunodeficiency; 2 are frequent: skin abnormalities and liver disease and 2 are rare: congenital cardiac defects and platelet anomaly. [1][2][3][4][5][6][7][8][9][10][11][12][13][14] The phenotypic presentation of THE-S is heterogeneous, and ranges from mild to severe form, which is characterized with long-term parenteral nutrition, and in some patients, typically it lasts for months to years, to achieve adequate nutrition and growth. 12 However, longterm parenteral nutrition should not be started in patients with concomitant liver disease.…”

Diarrea crónica intratable asociada con diarrea fenotípica de la infancia (síndrome tricohepatoentérico)

“…Verloes y sus colegas describieron la diarrea fenotípica de la infancia o síndrome tricohepatoentérico como diarrea intratable con fenotipo de hemocromatosis neonatal y anormalidades en el pelo. 3 Se han agrupado en un solo síndrome porque las características clínicas principales son idénticas. Varios autores han identificado mutaciones en el gen TTC37 en 21 individuos con el análisis de mapeo homocigoto después de realizar arreglo de polimorfismo de nucleó-tido único (SNP por sus siglas en inglés); dicho gen fue identificado en el locus 5q14.3-5q21.2 y codifica una proteína repetida, tetratricopeptí-dica no caracterizada llamada thespin (proteína del síndrome tricohepatoentérico por sus siglas en inglés).…”