Alagille Syndrome: Cutaneous Manifestations in 38 Children

Abstract

The Alagille syndrome is one of the most common inherited disorders causing chronic liver disease during childhood. During the 1990s, 38 children with Alagille syndrome were evaluated at two pediatric centers in Buenos Aires, Argentina. Characteristic clinical, humoral, and cutaneous features were analyzed. The average age of diagnosis was 29 months old (range of between 2 months and 15 years). Cholestasis was evident in 92% of patients during the neonatal period. Family antecedents related to the syndrome were found in 18.5% of the patients. Peculiar facies developed in 85% of patients. Chronic cholestasis and pruritus were observed in all of the patients and jaundice was evident in 78%. Eighty-four percent of the patients had heart disease (pulmonary stenosis, intraauricular communication, intraventricular communication), 76% of them showed growth retardation, and vertebrae abnormalities were found in 63%. Embryotoxon appeared in 76% of patients, and renal disturbances in 21%. Eleven children (28%) had xanthomas, in the neck, elbows, palms, helixes, inguinal area, gluteus, and knees. The earliest findings appeared in the first months of life, and the latest at 5 years of age. The xanthomas located in the folds had a stony aspect. Cholesterol levels ranging from 220 to 1600 mg percentage (mg%) were demonstrated in all of the children with xanthomas. Liver transplantation was performed in seven of the patients (18.4%). Two of them died after this operation. The disappearance of xanthomas after transplantation was remarkable in all of the patients.

Intense pruritus and failure to thrive in Alagille syndrome

“…Other sites include palmar creases, nape of neck, elbows, knees, perianal and gluteal areas, popliteal fossae, and inguinal folds. 1,7,9 To our knowledge, there is only one case report of oral xanthomas (gingival and palatal) in association with S10 Schwartz et al widespread eruptive xanthomas and tendon xanthomas. 10 In most reports, xanthomas are associated with prolonged and severe cholestasis levels ([17 mol/L or [1 mg/dL).…”

Você conhece esta síndrome?

“…A presença de um ou mais critérios (excluindo a fácies típica) é suficiente para se considerar o diagnóstico,≈ sendo síndrome completa a presença simultânea dos cinco critérios descritos. 1,3 Outros achados incluem atraso no desenvolvimento, alterações renais e ósseas, retardo mental e voz estridente.…”

“…1,5 Progressão para cirrose e insuficiência hepática ocorre em proporção significativa de pacientes, e cerca de 15% deles necessitam de transplante hepático.Δ Os achados laboratoriais incluem aumento de ácidos graxos, da bilirrubina conjugada, fosfatase alcalina, colesterol e gama-GT (indicativa de defeito na excreção biliar). Menos freqüentemente pode-se detectar aumento das aminotransferases e dos triglicérides.…”

“…1,4 Outros diagnósticos diferenciais mais raros são síndrome de Byler, síndrome de Aegenaes (colestase norueguesa autossômica recessiva) e sín-drome de Zellweger.≈…”

Analysis of JAG1 gene variant in Chinese patients with Alagille syndrome

“…It is one of the most common causes of pediatric chronic liver disease and occurs with a minimal estimated frequency of 1 in 70,000 to 100,000 newborn infants with no gender differentiation (Garcia et al, 2005). The phenotypic findings associated with AGS are highly variable, ranging from an apparently normal phenotype to severe cases in which liver failure requires transplantation (Crosnier et al, 2000).…”