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JIMD Reports Nov 2022Mucopolysaccharidoses (MPSs) and mucolipidosis II and III (ML II and III) often manifest with orofacial (progressive) abnormalities, which may have a major impact on...
Mucopolysaccharidoses (MPSs) and mucolipidosis II and III (ML II and III) often manifest with orofacial (progressive) abnormalities, which may have a major impact on quality of life. However, because these patients have multiple somatic health issues, orofacial problems are easily overlooked in clinical practice and available literature on this topic solely consists of case reports, small case series, and small cohort studies. The aim of this systematic review was to gain more insight in the nature and extent of orofacial abnormalities in MPS, ML II, and III. A systematic review of all previously published articles addressing orofacial abnormalities in MPS, ML II, and III was performed. Both clinical studies and case reports were included. Outcome was the described orofacial abnormalities, subdivided into abnormalities of the face, maxilla, mandible, soft tissues, teeth, and occlusion. The search resulted in 57 articles, describing orofacial features in 340 patients. Orofacial abnormalities were present in all subtypes of MPS, ML II, and III, and consisted of thickened lips, a hypoplastic midface, a high-arched palate, hypoplastic condyles, coronoid hyperplasia, macroglossia, gingival hyperplasia, thick dental follicles, dentigerous cysts, misshapen teeth, enamel defects, and open bite. Orofacial abnormalities are present in all subtypes of MPS, ML II, and III. As orofacial abnormalities may cause complaints, evaluation of orofacial health should be part of routine clinical care.
PubMed: 36341168
DOI: 10.1002/jmd2.12331 -
Genetics in Medicine : Official Journal... Nov 2021Mucolipidosis (ML) II, MLIII alpha/beta, and MLIII gamma are rare autosomal recessive lysosomal storage disorders. Data on the natural course of the diseases are scarce....
PURPOSE
Mucolipidosis (ML) II, MLIII alpha/beta, and MLIII gamma are rare autosomal recessive lysosomal storage disorders. Data on the natural course of the diseases are scarce. These data are important for counseling, therapies development, and improvement of outcome. The aim of this study is to gain knowledge on the natural history of ML by obtaining data on survival, symptom onset, presenting symptoms, diagnosis, and pathogenic variants associated with the MLII or MLIII phenotype.
METHODS
A systematic review on all published MLII and MLIII cases between 1968 and August 2019 was performed.
RESULTS
Three hundred one articles provided data on 843 patients. Median age at diagnosis: 0.7 for MLII and 9.0 years for MLIII. Median survival: 5.0 for MLII and 62.0 years for MLIIIII. Median age of death: 1.8 for MLII and 33.0 years for MLIII. Most frequent causes of death in all ML were pulmonary and/or cardiac complications. Pathogenic variants were described in 388 patients (GNPTAB: 571, GNPTG 179).
CONCLUSION
This review provides unique insights into the natural history of MLII and MLIII, with a clear genotype-phenotype correlation with the most frequent pathogenic variant c.3503_3504del in MLII and in MLIII alpha/beta c.22A>G for GNPTAB. All pathogenic GNPTG variants resulted in MLIII gamma.
Topics: Genetic Association Studies; Humans; Mucolipidoses; Phenotype; Transferases (Other Substituted Phosphate Groups)
PubMed: 34172897
DOI: 10.1038/s41436-021-01244-4 -
Journal of Pediatric Gastroenterology... Jun 2021Congenital diarrhea and enteropathies linked to epithelial structural abnormalities constitute 3 different rare diseases: the tufting enteropathies (TE; EPCAM and SPINT2...
OBJECTIVES
Congenital diarrhea and enteropathies linked to epithelial structural abnormalities constitute 3 different rare diseases: the tufting enteropathies (TE; EPCAM and SPINT2 mutations), microvillous inclusion disease (MVID; MYO5B and STX3 mutations), and tricho-hepato-enteric syndrome (THE; TTC37 and SKIV2L mutations). Moreover, enteroendocrine deficiencies (ED; PCSK1 and NEUROG3 mutations) share common clinical characteristics with TE, THE, and MVID in that the treatment requires, in most cases, long-term parenteral nutrition. Although numerous cases have been reported in the literature, aggregated data on morbidity and mortality are missing owing to the rarity of the diseases.
METHODS
We performed a systematic review of all published cases and retrieved 86 articles describing 323 patients (164 boys and 135 girls).
RESULTS
The mortality rate was 20.28%, with a median age at death of 13.5 months (range 0-228 months); the mortality risk was 30.8/1000 person-year; in half of the cases, death was caused by infections. Parenteral nutrition was required in 95.4% of patients and weaning off from parenteral nutrition was achieved in 29.35% at a median age of 23 months (range 3.3-276 months). The patients with ED linked to PCSK1 were nearly all weaned at a median age of 14 months, but most of the patients became overweight. MVID patients with MYO5B mutations were most often born preterm. ED linked to NEUROG3 mutation and THE patients usually presented with intrauterine growth retardation.
CONCLUSIONS
This review presents data from 323 patients with congenital diarrhea linked to EPCAM TE, SPINT2 TE, TTC37 THE, SKIV2L THE, MYO5B MVID, STX3 MVID, NEUROG3 ED, and PCSK1 ED mutations.
Topics: Diarrhea, Infantile; Female; Humans; Infant; Infant, Newborn; Intestinal Diseases; Malabsorption Syndromes; Male; Membrane Glycoproteins; Microvilli; Mucolipidoses
PubMed: 33976085
DOI: 10.1097/MPG.0000000000003049 -
Neuroradiology Jul 2007Lysosomal disorders are rare and are caused by genetically transmitted lysosomal enzyme deficiencies. A decreased T2 signal in the thalamus has occasionally been... (Review)
Review
INTRODUCTION
Lysosomal disorders are rare and are caused by genetically transmitted lysosomal enzyme deficiencies. A decreased T2 signal in the thalamus has occasionally been reported.
AIMS
Because the finding of bilateral abnormal signal intensity of the thalamus on T2-weighted images has not been systematically reviewed, and its value as a diagnostic tool critically evaluated, we carried out a systematic review of the literature.
METHODS
Articles in English with 30 trios of keywords were collected from PubMed. Exclusion criteria were lack of conventional T2-weighted images in the protocol and not being a human study. Finally, 111 articles were included. The thalamus was considered affected only if mentioned in the text or in the figure legends.
RESULTS
Some 117 patients with various lysosomal diseases and five patients with ceruloplasmin deficiency were reported to have a bilateral decrease in T2 signal intensity. At least one article reported a bilateral decrease in signal intensity of the thalami on T2-weighted images in association with GM1 and GM2 gangliosidosis and with Krabbe's disease, aspartylglucosaminuria, mannosidosis, fucosidosis, and mucolipidosis IV. Furthermore, thalamic alteration was a consistent finding in several types of neuronal ceroid lipofuscinosis (NCL) including CLN1 (infantile NCL), CLN2 (classic late infantile NCL), CLN3 (juvenile NCL), CLN5 (Finnish variant late infantile NCL), and CLN7 (Turkish variant late infantile NCL).
CONCLUSION
A decrease in T2 signal intensity in the thalami seems to be a sign of lysosomal disease.
Topics: Humans; Lysosomal Storage Diseases, Nervous System; Magnetic Resonance Imaging; Thalamus; Tripeptidyl-Peptidase 1
PubMed: 17334752
DOI: 10.1007/s00234-007-0220-6 -
Journal of Inherited Metabolic Disease May 2018Significant improvements in automated image analysis have been achieved in recent years and tools are now increasingly being used in computer-assisted syndromology....
Significant improvements in automated image analysis have been achieved in recent years and tools are now increasingly being used in computer-assisted syndromology. However, the ability to recognize a syndromic facial gestalt might depend on the syndrome and may also be confounded by severity of phenotype, size of available training sets, ethnicity, age, and sex. Therefore, benchmarking and comparing the performance of deep-learned classification processes is inherently difficult. For a systematic analysis of these influencing factors we chose the lysosomal storage diseases mucolipidosis as well as mucopolysaccharidosis type I and II that are known for their wide and overlapping phenotypic spectra. For a dysmorphic comparison we used Smith-Lemli-Opitz syndrome as another inborn error of metabolism and Nicolaides-Baraitser syndrome as another disorder that is also characterized by coarse facies. A classifier that was trained on these five cohorts, comprising 289 patients in total, achieved a mean accuracy of 62%. We also developed a simulation framework to analyze the effect of potential confounders, such as cohort size, age, sex, or ethnic background on the distinguishability of phenotypes. We found that the true positive rate increases for all analyzed disorders for growing cohorts (n = [10...40]) while ethnicity and sex have no significant influence. The dynamics of the accuracies strongly suggest that the maximum distinguishability is a phenotype-specific value, which has not been reached yet for any of the studied disorders. This should also be a motivation to further intensify data sharing efforts, as computer-assisted syndrome classification can still be improved by enlarging the available training sets.
Topics: Adolescent; Algorithms; Child; Facies; Female; Foot Deformities, Congenital; Humans; Hypotrichosis; Image Processing, Computer-Assisted; Intellectual Disability; Male; Metabolism, Inborn Errors; Molecular Diagnostic Techniques; Phenotype; Smith-Lemli-Opitz Syndrome; Syndrome
PubMed: 29623569
DOI: 10.1007/s10545-018-0174-3