UNASSIGNED: X-linked adrenoleukodystrophy (ALD) is a rare genetic disorder caused by a pathogenic variant of the ABCD1 gene, leading to impaired peroxisomal function and the accumulation of very long-chain fatty acids (VLCFAs). ALD presents a wide range of neurological and adrenal symptoms, ranging from childhood cerebral adrenoleukodystrophy to adrenomyeloneuropathy and adrenal insufficiency. Newborn screening (NBS) for ALD is available in some regions but remains lacking in others, such as India.
UNASSIGNED: We present a case of a 10-year-old boy with ALD who presented with seizures, progressive weakness, visual impairment, and adrenal insufficiency. Despite symptomatic management and dietary adjustments, the disease progressed rapidly, leading to respiratory failure and eventual demise. The diagnosis was confirmed through molecular analysis and elevated VLCFA levels. Neuroimaging revealed characteristic white matter changes consistent with ALD.
UNASSIGNED: ALD is a devastating disease with no cure, emphasizing the importance of early detection through newborn screening and genetic testing. Management strategies include adrenal hormone therapy, gene therapy, and allogenic stem cell transplantation, as well as investigational treatments such as VLCFA normalization. Our case advocates the need for worldwide NBS and pediatric neurologic follow-up to enable early intervention and improve patient outcomes. Additionally, the association between ALD, recurrent febrile seizures, and unexplained developmental delay warrants further investigation to better understand disease progression and potential therapeutic targets.

Wilson disease (WD) is an autosomal recessive disorder of copper metabolism. The clinical manifestations of WD are complex and variable, with Kayser-Fleischer ring (K-F ring) and the sunflower cataract being the most common ocular findings. Visual impairment is rare in patients with WD. We report the case of a 17-year-old female with bilateral optic atrophy associated with WD and summarize the clinical features of previously reported cases of optic neuropathy in WD, Clinicians should be aware that WD is a rare cause of optic neuropathy and that optic neuropathy in patients with WD may need to be recognized and screened.

UNASSIGNED: Biotinidase deficiency (BD) is an inherited autosomal recessive metabolic disorder. BD has been associated with optic nerve atrophy, eye infections, and retinopathy. The most prevalent ophthalmic manifestation of BD is optic atrophy, which might be misdiagnosed as multiple sclerosis or neuromyelitis optica, especially in late-onset BD cases.
UNASSIGNED: In this article, we report a 9-year-old boy with gradual vision loss. Ophthalmologic examination, Brain MRI, and several laboratory tests such as Aquaporin-4 IgG level and biotinidase level were done on the patient.
UNASSIGNED: Bilateral optic atrophy and impaired visual acuity were detected on examination. The patient had a biotin level of 1.25 U/min/ml (normal range 3-9 U/min/ml), favoring the BD.
UNASSIGNED: In this study, we report a 9-year-old boy with vision loss diagnosed with BD. We also reviewed the literature to highlight the ophthalmic manifestations of BD. Ophthalmologists must consider BD in children with unexplained ophthalmologic complaints, especially when other characteristic signs of BD (e.g., developmental delay, seizure) are present. Also, patients with BD should undergo regular annual ophthalmologic examinations to be checked for any signs of eye involvement.

UNASSIGNED: There are very few reports of Wolfram syndrome-2 (WFS2) in the literature, and understanding of involvement of the gastrointestinal (GI) tract in the syndrome is limited. Objectives: This study aims to describe the clinical presentations of a large number of WFS2 patients with specific focus on their GI manifestations.
UNASSIGNED: This is a retrospective case series study. Patients who were homozygous for the CISD2 gene mutation were identified through the genetic department of Al-Makassed hospital. Their medical records were reviewed, and biometric data have been obtained. The data were collected and arranged on a data sheet, and descriptive analysis was done using SPSS.
UNASSIGNED: Thirteen patients from 9 families were identified; diabetes mellitus was present in 6 of them, optic atrophy in 5, diabetes insipidus (DI) in 5, and deafness in 2. All of the patients had GI manifestations with abnormal findings on upper endoscopy. Dysmorphic facial features and abnormal findings on brain MRI were present in 3 of our patients. The GI manifestations including GI bleeding and severe ulcerations were the first to appear in 9 of them, while anemia in the remaining 4.
UNASSIGNED: This is the largest study to date describing patients with WFS2. This study\'s evidence shows the prominent presence of GI involvement, and the severe findings on endoscopy, including duodenal, gastric, and esophageal ulcerations and strictures. Unlike in the Jordanian report, some of the patients in our report also have DI.

Wolfram syndrome is a neurodegenerative disorder caused by pathogenic variants in the genes WFS1 or CISD2. Clinically, the classic phenotype is composed of optic atrophy, diabetes mellitus type 1, diabetes insipidus, and deafness. Wolfram syndrome, however, is phenotypically heterogenous with variable clinical manifestations and age of onset. We describe four cases of genetically confirmed Wolfram syndrome with variable presentations, including acute-on-chronic vision loss, dyschromatopsia, and tonic pupils. All patients had optic atrophy, only three had diabetes, and none exhibited the classic Wolfram phenotype. MRI revealed a varying degree of the classical features associated with the syndrome, including optic nerve, cerebellar, and brainstem atrophy. The cohort\'s genotype and presentation supported the reported phenotype-genotype correlations for Wolfram, where missense variants lead to milder, later-onset presentation of the Wolfram syndrome spectrum. When early onset optic atrophy and/or diabetes mellitus are present in a patient, a diagnosis of Wolfram syndrome should be considered, as early diagnosis is crucial for the appropriate referrals and management of the associated conditions. Nevertheless, the condition should also be considered in otherwise unexplained, later-onset optic atrophy, given the phenotypic spectrum.

The options for genetic testing continue to grow for ocular conditions, including optic atrophy, anterior segment dysgenesis, cataracts, corneal dystrophy, nystagmus, and glaucoma. Gene panels can vary in content and coverage, as we and others have evaluated in inherited retinal disease (IRD).
To describe gene panel testing options for inherited eye disease phenotypes and their differences. This review is important for making diagnostic decisions.
A licensed, certified genetic counselor (RP) used Concert Genetics and the search terms optic atrophy, corneal dystrophy, cataract, glaucoma, anterior segment dysgenesis, microphthalmia/anophthalmia, and nystagmus to identify available testing options performed by CLIA-certified commercial genetic testing laboratories. Other co-authors were surveyed with respect to genetic panels used for the indications of interest. Ophthalmic panels were then compared using Concert Genetics in addition to their own websites.
Panels from each clinical category were included and summarized. This comparison highlighted the differences and similarities between panels so that clinicians can make informed decisions.
Access to genetic testing is increasing. The diagnostic yield of genetic testing is increasing. Each panel is different, so phenotyping or characterizing clinical characteristics that may help predict a specific genotype, as well as pre-test hypotheses regarding a genotype, should shape the choice of panels.

Since the first report of SOPH syndrome among the Yakut population in 2010, new clinical data of SOPH-like conditions continue to appear. We expand the phenotypic spectrum of SOPH syndrome and perform a comparative analysis of Yakut SOPH patients\' clinical data with SOPH-like conditions reported in the world scientific literature to form a foundation for NBAS pathogenesis discussion. Clinical data from the genetic records of 93 patients with SOPH syndrome and global survey data on patients with pathogenic variants of the C-terminal in the NBAS gene were collected. A detailed phenotype description of patients is presented with a total number of 111 individuals. Underweight below the fifth centile and prone to delayed bone age in Yakut SOPH patients are retrospectively observed. We outline the short stature with optic atrophy as the leading phenotyping trait for C-terminal NBAS patients. The pathophysiology and patients management of SOPH-like conditions are discussed.

Wolfram-like syndrome (WFLS) is a recently described autosomal dominant disorder with phenotypic similarities to autosomal recessive Wolfram syndrome (WS), including optic atrophy, hearing impairment, and diabetes mellitus. We summarize current literature, define the clinical characteristics, and investigate potential genotype phenotype correlations. A systematic literature search was conducted in electronic databases Pubmed/MEDLINE, EMBACE, and Cochrane Library. We included studies reporting patients with a clinical picture consisting at least 2 typical clinical manifestations of WSF1 disorders and heterozygous mutations in WFS1. In total, 86 patients from 35 studies were included. The most common phenotype consisted of the combination of optic atrophy (87%) and hearing impairment (94%). Diabetes mellitus was seen in 44% of the patients. Nineteen percent developed cataract. Patients with missense mutations in WFS1 had a lower number of clinical manifestations, less chance of developing diabetes insipidus, but a younger age at onset of hearing impairment compared to patients with nonsense mutations or deletions causing frameshift. There were no studies reporting decreased life expectancy. This review shows that, within the spectrum of WFS1-associated disorders or \"wolframinopathies,\" autosomal dominantly inherited WFLS has a relatively mild phenotype compared to autosomal recessive WS. The clinical manifestations and their age at onset are associated with the specific underlying mutations in the WFS1 gene.

Wolfram syndrome (WS) is a rare genetic disorder typically characterized by juvenile onset diabetes mellitus, optic atrophy, hearing loss, diabetes insipidus, and neurodegeneration. There would be a high index of clinical suspicion for WS when clinical manifestations of type 1 diabetes and optic atrophy present together. Genetic analysis is often required to confirm the diagnosis. We describe a pair of Chinese siblings diagnosed with WS at ages 20 and 24 years, respectively. DNA sequencing of the WFS1 gene which encodes for Wolframin ER Transmembrane Glycoprotein identified a heterozygous nonsense variant NM_006005.3: c.1999C>T p.(Gln667*) and a heterozygous missense variant c.2170C>T p.(Pro724Ser) in exon 8 of the gene for both siblings. There is no curative treatment for WS and management of this debilitating disease is aimed at treating individual clinical manifestations, slowing disease progression, and improving quality of life. Treatment with liraglutide, a glucagon-like-peptide-1 receptor agonist, and tauroursodeoxycholic acid was started for the younger sibling, the proband. There was reduction in insulin requirements and improvement in glycemic control. The other sibling was not offered liraglutide due to her complex treatment regimen for end-organ failure. Genetic testing is a valuable tool to detect WS early to allow precise and prompt diagnosis, thereby facilitating the coordinated care from a multidisciplinary team of clinicians.

Objective: To investigate the clinical efficacy of liver transplantation in the treatment of acute liver in children with NBAS gene deficiency disease and their outcome. Methods: This retrospective study enrolled children with NBAS gene deficiency who were admitted to the Children\'s Hospital of Fudan University for liver transplantation from January 2013 to June 2022. The clinical data were collected and analyzed. Medical literature published before June 2022 was searched with the keywords of \"NBAS\" \"neuroblastoma amplified sequence recurrent\" \"acute liver failure\" \"SOPH syndrome\" \"short stature with optic nerve atrophy\" \"Pelger-Huët anomaly\" in PubMed, China National Knowledge Infrastructure and Wanfang database. Results: Liver transplantation was performed in 3 patients (2 males and 1 female) with NBAS deficiency. All patients presented with fever-triggered recurrent acute liver failure. The genetic detection found compound heterozygous NBAS gene pathogenic variants in them. The total episodes of acute liver failure before liver transplantation were 11, 2, and 4 respectively, and the age at liver transplantation was 3.5, 2.3, and 2.0 years respectively. During liver transplantation, patient 1 was in the convalescent phase of acute liver failure, patient 2 was in the acute phase, presenting with hepatic encephalopathy (grade V) and respiratory failure, and patient 3 was considered to be in the acute phase. After liver transplantation, patient 1 recovered normal liver function within 1 month and had no liver transplantation-related complications. Patient 2 had secondary epilepsy, intellectual disability, movement disorder, and transiently elevated transaminases. Patient 3 died of severe infection within 1 month. There was no literature in Chinese, 6 in English, 8 NBAS-deficient patients who were treated with liver transplantation. Total 11 patients presented with fever-triggered recurrent acute liver failure. Their age at liver transplantation ranged from 0.9 to 5.0 years. Postoperative complications occurred in 3 patients. Until the last visit, they were followed up for 0.7 to 14.0 years. Total 2 patients died and the 9 surviving patients did not develop acute liver failure. Conclusions: Liver transplantation is effective for the treatment of acute liver failure associated with NBAS gene disease. However, postoperative complications of liver transplantation may occur. The timing of liver transplantation still needs further research.
目的： 探讨肝移植治疗儿童NBAS基因缺陷病急性肝衰竭的临床疗效和预后。 方法： 回顾性病例总结2013年1月至2022年6月就诊于复旦大学附属儿科医院并行肝移植手术的3例NBAS基因缺陷病患儿的临床资料，并分别以“NBAS”“neuroblastoma amplified sequence recurrent”“acute liver failure”“SOPH syndrome”“short stature with optic nerve atrophy and Pelger-Huët anomaly”“发热相关肝衰竭”“急性肝衰竭”为关键词检索PubMed、万方数据库、中国知网数据库建库至2022年6月关于NBAS基因缺陷病肝移植的病例报道，总结其临床疗效和预后。 结果： 3例NBAS基因缺陷病患儿行肝移植治疗，男2例，女1例。3例患儿临床表型为发热相关的反复急性肝衰竭，基因结果为NBAS基因复合杂合致病变异。肝移植前急性肝衰竭次数分别为11、2和4次，手术年龄分别为3.5、2.3和2.0岁。肝移植时，例1为肝衰竭恢复期，例2为肝衰竭急性期肝性脑病Ⅴ期和呼吸衰竭，例3可能为肝衰竭急性期。肝移植后，例1于1个月内肝功能恢复正常，无术后并发症。例2出现癫痫、精神运动发育落后和暂时性转氨酶升高。例3于1个月内死于脓毒症。文献检索未见中文文献，6篇英文文献报道8例行肝移植手术的NBAS基因缺陷病患儿。结合本组3例患儿，11例患儿均表现为发热相关的反复急性肝衰竭，肝移植年龄为0.9~5.0岁。3例患儿出现术后并发症。截至末次随访，11例患儿随访时间为0.7~14.0年，2例患儿死亡，9例患儿存活并无肝衰竭。 结论： 肝移植是治疗NBAS基因缺陷病肝衰竭有效的措施，但术后可能出现肝移植相关并发症，NBAS基因缺陷肝衰竭肝移植时机仍需进一步研究。.