Leber’s Congenital Amaurosis as the Retinal Degenerative Phenotype in Thiamine Responsive Megaloblastic Anemia: A Case Report

Srikrupa, Natarajan N.; Swaminathan, M. S.; Arokiasamy, Tharigopala; Murali, Kaushik; Soumittra, Nagasamy

doi:10.3109/13816810.2013.793363

Cited by 12 publications

(8 citation statements)

References 29 publications

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“…RPGR variants, associated with X-linked inheritance, which manifest retinitis pigmentosa, hearing loss, sinusitis and chronic respiratory tract infection, also shares many phenotypic features with USH (Zito et al 2003). In a case report of one individual with Leber's congenital amaurosis, typically associated with poor vision, SNHL, diabetes mellitus, and megaloblastic anemia, poor vision and hearing loss were noted by 1 year of age, while anemia and diabetes were noticed later (Srikrupa et al 2014). Although it is challenging to differentiate these genetic syndromes from USH at early ages based on clinical presentation alone, an accurate diagnosis is crucial to families and clinicians as it will guide audiologic and ophthalmologic habilitation and prepare the family for complications such as anemia and diabetes.…”

Section: Discussionmentioning

confidence: 99%

“…Importantly, there are a number of other frequently overlooked genes associated with both hearing loss diagnosed in early childhood and visual impairment that may warrant distinct clinical management. Examples include CEP78 , associated with cone-rod dystrophy and deafness; SLC19A2 , associated with Leber's congenital amaurosis; and PEX1 and PEX6 , associated with Heimler syndrome ( Srikrupa et al 2014 ; Nikopoulos et al 2016 ; Wangtiraumnuay et al 2018 ).…”

Section: Introductionmentioning

confidence: 99%

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Hiding in plain sight: genetic deaf-blindness is not always Usher syndrome

Medina

Perry

Oza

et al. 2021

Cold Spring Harb Mol Case Stud

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Introduction: Hearing loss (HL) is the most common congenital sensory impairment. Usher syndrome (USH) is the leading genetic etiology of congenital deafness combined with progressive vision loss, and individuals presenting with these symptoms are often assumed to have USH. This can be an erroneous assumption, as there are additional genetic causes of deafblindness.Objective: To describe and accurately diagnose non-USH genetic causes of deaf-blindness.Methods: We present three children with hearing and vision loss with clinical and genetic findings suggestive of USH. However, ongoing clinical assessment did not completely support an USH diagnosis, and exome analysis was pursued for all three individuals.Results: Updated genetic testing showed pathogenic variants in ALMS1 in the first individual and TUBB4B in the second and third. Although HL in all three was consistent with USH type 2, vision impairment with retinal changes was noted by age two years, which is unusual for USH.In all three the updated genotype more accurately fit the clinical phenotype. Conclusion:Because USH is the most common form of genetic deaf-blindness, individuals with HL, early vision impairment, and retinal dysfunction are often assumed to have USH. However, additional genes associated with HL and retinal impairment include ALMS1, TUBB4B, CEP78, ABHD12, and PRPS1. Accurate genetic diagnosis is critical to these individuals' understanding of their genetic conditions, prognosis, vision and hearing loss management, and future access to molecular therapies. If clinically or genetically USH seems uncertain, updated genetic testing for non-USH genes is essential.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hiding in plain sight: genetic deaf-blindness is not always Usher syndrome

Medina

Perry

Oza

et al. 2021

Cold Spring Harb Mol Case Stud

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“…In addition, there are some unusual manifestations, including stroke-like onset, thrombocytopenia, ataxia, liver enlargement, arrhythmia, retinal degeneration, and short stature [2,3]. These clinical manifestations, however, are unspecific, and genetic testing is believed to be a TRMA-specific diagnostic method.…”

Section: Introductionmentioning

confidence: 99%

A Novel Mutation of SLC19A2 in a Chinese Zhuang Ethnic Family with Thiamine-Responsive Megaloblastic Anemia

Xian

Liao

Shu

et al. 2018

Cell Physiol Biochem

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Background/Aims: Thiamine-responsive megaloblastic anemia syndrome is a rare autosomal recessive disorder resulting from mutations in SLC19A2, and is mainly characterized by megaloblastic anemia, diabetes, and progressive sensorineural hearing loss. Methods: We study a Chinese Zhuang ethnicity family with thiamine-responsive megaloblastic anemia. The proband of the study presented with anemia and diabetes, similar to his late brother, as well as visual impairment. All clinical manifestations were corrected with thiamine (30 mg/d) supplementation for 1–3 months, except for visual impairment, which was irreversible. The presence of mutations in all exons and the flanking sequences of the SLC19A2 gene were analyzed in this family based on the proband’s and his brother’s clinical data. Computer analysis and prediction of the protein conformation of mutant THTR-1. The relative concentration of thiamine pyrophosphate in the proband’s whole blood before and after initiation of thiamine supplement was measured by high performance liquid chromatography (HPLC). Results: Gene sequencing showed a homozygous mutation in exon 6 of the SLC19A2 gene (c.1409insT) in the proband. His parents and sister were diagnosed as heterozygous carriers of the c.1409insT mutation. Computer simulation showed that the mutations caused a change in protein conformation. HPLC results suggested that the relative concentration of thiamine pyrophosphate in the proband’s whole blood after thiamine supplement was significantly different (P=0.016) from that at baseline. Conclusions: This novel homozygous mutation (c.1409insT) caused the onset of thiamine-responsive megaloblastic anemia in the proband.

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“…Affected infants show signs of night blindness, roving/pendular nystagmus, photophobia, and digito-ocular signs that are characterized by a nonrecordable electroretinogram (ERG) 1 . Accounting for 10-20% of childhood blindness, LCA is clinically heterogeneous; indeed, it is reported as an isolated clinical entity as well as in certain syndromes, such as Joubert syndrome 2 , thiamine-responsive megaloblastic anemia 3 , Senior-Loken syndrome 4 , and Batten's disease 5 . Genetically, LCA is predominantly inherited as an autosomal recessive disease and rarely as an autosomal dominant disease.…”

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confidence: 99%

“…2 School of Chemical and Biotechnology, SASTRA deemed to-be University, Thanjavur, India. 3 Shri Bhagwan Mahavir Vitreoretinal Services, Medical Research Foundation, Sankara Nethralaya, Chennai, India. 4 MedGenome Labs Pvt.…”

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confidence: 99%

Whole-exome sequencing identifies two novel ALMS1 mutations in Indian patients with Leber congenital amaurosis

et al. 2021

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Leber congenital amaurosis (LCA) is a severe autosomal recessive retinal degenerative disease. The current study describes exome sequencing results for two unrelated Indian LCA patients carrying novel nonsense p.(Glu636*) and frameshift p.(Pro2281Leufs*63) mutations in the ALMS1 gene. Although ALMS1 gene mutations are associated with Alstrom syndrome (AS), the current patients did not exhibit typical syndromic features of AS. These data suggest that ALMS1 should be included in the candidate gene panel for LCA to improve diagnostic efficiency.

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Leber’s Congenital Amaurosis as the Retinal Degenerative Phenotype in Thiamine Responsive Megaloblastic Anemia: A Case Report

Cited by 12 publications

References 29 publications

Hiding in plain sight: genetic deaf-blindness is not always Usher syndrome

Hiding in plain sight: genetic deaf-blindness is not always Usher syndrome

A Novel Mutation of SLC19A2 in a Chinese Zhuang Ethnic Family with Thiamine-Responsive Megaloblastic Anemia

Whole-exome sequencing identifies two novel ALMS1 mutations in Indian patients with Leber congenital amaurosis

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