Dual diagnosis of Ochoa syndrome and Niemann-Pick disease type B in a consanguineous family

Abstract

Objectives Ochoa syndrome (UFS1; Urofacial syndrome-1) is a very rare autosomal recessive disorder caused by mutations in the HPSE2 gene that results bladder voiding dysfunction and somatic motor neuropathy affecting the VIIth cranial nerve. Niemann-Pick disease is a rare autosomal recessive lysosomal storage disorder with systemic involvement resulting from sphingomyelinase deficiency and generally occurs via mutation in the sphingomyelin phosphodiesterase-1 gene (SMPD1). Case presentation Here, we report a 6-year-old girl with symptoms such as urinary incontinence, recurrent urinary tract infections, peculiar facial expression, mainly when smiling, hypertelorism, constipation, incomplete closure of eyelids during sleep and splenomegaly. Homozygote mutations in two different genes responsible for two distinct syndromes were detected in the patient. Homozygous NM_000543.5:c.502G>A (p.Gly168Arg) mutation was found in the SMPD1 gene causing Niemann-Pick disease. In addition, some of the clinical features were due to a novel homozygous mutation identified in the HPSE2 gene, NM_021828.5:c.755delA (p.Lys252SerfsTer23). Conclusions Here, we discuss about the importance of considering dual diagnosis in societies where consanguineous marriages are common. Accurate diagnosis of the patient is very important for the management of the diseases and prevention of complications.

Expanding the HPSE2 Genotypic Spectrum in Urofacial Syndrome, A Disease Featuring a Peripheral Neuropathy of the Urinary Bladder

“…There is variability in phenotypic expression, even in a single family, and a small proportion of affected individuals may manifest only the grimace or urinary voiding dysfunction ( Newman and Woolf, 2018 ). Previous reports of pathogenic variants in HPSE2 feature stop-gain variants, splice variants and deletions ( Daly et al, 2010 ; Pang et al, 2010 ; Al Badr et al, 2011 ; Stuart et al, 2015 ; Bulum et al, 2015 ; Vivante et al, 2017 ; van der Ven et al, 2018 ; Cesur Baltacı et al, 202 1), all consistent with a loss of function mechanism. There exists only a single report of a homozygous missense, p.(Asn543Ile), in HPSE2 associated with UFS ( Mahmood et al, 2012 ).…”

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.…”

An adult with cystathionine beta-synthase deficiency, camptodactyly-arthropathy-coxa vara-pericarditis syndrome, and deafness: A case report

“…The concept of multilocus pathogenic variations (MPV) is relatively new, corresponding to the occurrence of two or more monogenic disorders in the same individual, which leads to complex phenotypes difficult to identify only by clinical or biochemical tests ( Baltaci et al, 2021 ; Correia-Costa et al, 2022 ; Herman et al, 2022 ). Since the advent of genome/exome sequencing, MPVs have been identified in 1.4% to 7.2% of patients with rare diseases ( Yang et al, 2013 , 2014 ; Posey et al, 2017 ; Correia-Costa et al , 2022 ).…”