Co-Occurring Atypical Galactosemia and Wilson Disease

Abstract

<b><i>Introduction:</i></b> Classic galactosemia is a disorder of the galactose metabolism and is inherited as an autosomal recessive disease. It is caused by a complete or severe deficiency of galactose-1-phosphate uridyltransferase (GALT), and in rare cases, atypical galactosemia can manifest at older ages. Wilson disease (WD) is a disorder of the copper metabolism that, like galactosemia, is inherited as an autosomal recessive disease. Hepatic, neurological, or psychiatric symptoms can be seen, independently or in combination, and symptoms vary from family to family. We present here a patient diagnosed with both WD and galactosemia. <b><i>Case Presentation:</i></b> A 6-year-old girl was referred to our center with elevated transaminase levels and hepatosplenomegaly. The child, birthweight of 2,200 g, was born to first-degree consanguineous parents after a full-term uneventful pregnancy and was hospitalized in the neonatal period due to indirect hyperbilirubinemia, gastrointestinal bleeding, diarrhea lasting 2 weeks, and elevated liver enzymes. Hepatosplenomegaly was evident at the time of admission, a cataract was detected, and a neuropsychiatric evaluation revealed borderline mental capacity, as well as cognitive and speech retardation. Metabolic investigations revealed no specific findings other than trace positivity of reducing substances in the urine. A liver biopsy revealed copper accumulation in hepatocytes and low ceruloplasmin levels. Although WD was suspected in the patient, this diagnosis did not explain the intellectual disability, behavioral disorder, or cataract findings. A genetic analysis revealed homozygous mutations in the <i>ATP7B</i> and <i>GALT</i> genes. The galactose-1-phosphate uridyltransferase enzyme level was found to be low, and the patient was diagnosed with coexisting WD and galactosemia. <b><i>Conclusion:</i></b> Coexistences of rare genetically transmitted diseases can be seen in countries where consanguineous marriages are common (Saudi Arabia, Iran, Pakistan, etc.), as in our country, Turkey.

Dual Molecular Diagnoses of Recessive Disorders in a Child from Consanguineous Parents: Case Report and Literature Review

“…Among these cases, 84 presented dual recessive diagnoses (AR + AR) and 22 presented multiple molecular diagnoses, with at least two recessive diagnoses (AR + AR + _). Furthermore, 72.64% (77 of 106) of these patients were known to be children of consanguineous parents [ 1 , 2 , 3 , 4 , 11 , 12 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ]. None of the reported cases carried recessive pathogenic variants simultaneously in the ASPM and CTNS genes, as the patient herein described.…”

Expanded Phenotypic Spectrum or Multiple Syndromes?

“…The latter phenotypes are consistent with autosomal recessive Alport syndrome. In a second article in this issue, a patient with co-occurring Wilson disease and atypical galactosemia is described [Doğulu et al, 2022]. Upon targeted sequencing of a panel of 450 genes for inherited metabolic diseases, a homozygous c.2293G>A (p.Asp765Asn) variant in the ATP7B gene was found.…”

“…In these cases the underlying genomic variants have been uncovered with genome-wide screening methods such as chromosomal arrays and whole-exome or whole-genome sequencing. Molecular Syndromology welcomes in particular such case reports combining in-depth, structured phenotyping with elucidation of multiple genomic variants by genome-wide methods [Farajzadeh Valilou et al, 2020;Demir et al, 2022;Doğulu et al, 2022].…”

Shifting the Focus of Molecular Syndromology from Individual Diagnoses to Outcome Analyses

“…CNVs were found in 11.9% of the patients with multiple diagnoses. Molecular Syndromology has already published several case reports on "dual diagnoses" and welcomes in particular such reports combining in-depth, structured phenotyping with elucidation of multiple genomic variants by genome wide methods [Farajzadeh Valilou et al, 2020;Demir et al, 2022;Doğulu et al, 2022;Izumi et al, 2023, in this issue].…”