JIMD reports最新文献

{"title":"Reduced guanidinoacetate in plasma of patients with autosomal dominant Fanconi syndrome due to heterozygous P341L GATM variant and study of organoids towards treatment","authors":"Ignacio Portales-Castillo,&nbsp;Rhea Singal,&nbsp;Anastasia Ambrose,&nbsp;Jong Hee Song,&nbsp;Minsoo Son,&nbsp;Young Ah. Goo,&nbsp;Wen Zhou,&nbsp;Avram Z. Traum,&nbsp;Ariella Coler-Reilly,&nbsp;Benjamin D. Humphreys,&nbsp;Roberto Civitelli,&nbsp;Harald Jüppner,&nbsp;Andrew L. Lundquist,&nbsp;Peter Seres,&nbsp;Andrew S. Allegretti,&nbsp;Saadet Mercimek-Andrews","doi":"10.1002/jmd2.12442","DOIUrl":"https://doi.org/10.1002/jmd2.12442","url":null,"abstract":"<p>Autosomal dominant Fanconi syndrome due to a <i>GATM</i> variant (GATM-FS), causes accumulation of misfolded arginine-glycine amidinotransferase (AGAT) in proximal renal tubules leading to cellular injury. GATM-FS presents during childhood and progresses to end-stage kidney disease (ESKD) in adults. We study creatine metabolism in two individuals of unrelated families with a known <i>GATM</i> variant and the effect of creatine supplementation in kidney organoids. Plasma and urine metabolites were measured by mass spectrometry. Brain creatine was assessed by magnetic resonance spectroscopy (MRS). Guanidinoacetate (GAA) synthesis by the AGAT mutant was measured in patient-derived immortalized lymphocytes using stable isotopes of arginine and glycine. The effect of creatine on <i>GATM</i> expression was assessed in human kidney cells and organoids. Several family members from two unrelated families were diagnosed with Fanconi syndrome and had the c.1022C&gt;T (p. P341L) variant in <i>GATM</i>. Two affected individuals in both families had moderately reduced plasma GAA levels. In comparison to wild-type cells, GAA synthesis by patient-derived <i>GATM</i>^P341L+/− lymphoblastoid cell lines (LCL) was reduced, but not absent as in <i>GATM</i> cells from a patient with creatine deficiency syndrome. In vitro studies on human kidney organoids revealed reduced AGAT expression after treatment with creatine. Finally, we showed in one patient that creatine supplementation (5 g daily) substantially increased plasma creatine levels. We report low plasma and urine GAA in patients with autosomal dominant GATM-FS and show that creatine downregulates AGAT in human kidney cells.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"65 5","pages":"341-353"},"PeriodicalIF":0.0,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmd2.12442","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142165771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gaucher disease type 3c: Expanding the clinical spectrum of an ultra-rare disease","authors":"John S. Wang,&nbsp;Rebecca L. Koch,&nbsp;Daniel Kenney-Jung,&nbsp;Erin Huggins,&nbsp;Sirajbir S. Sodhi,&nbsp;Andrew P. Landstrom,&nbsp;Dilraj S. Grewal,&nbsp;Priya S. Kishnani","doi":"10.1002/jmd2.12440","DOIUrl":"https://doi.org/10.1002/jmd2.12440","url":null,"abstract":"<p>Gaucher disease (GD) type 3 is an autosomal recessive lysosomal disease caused by deficiency of β-glucocerebrosidase (GCase) and encompasses a spectrum of cardiac, neurological, and ophthalmological abnormalities. Although the clinical presentations can be diverse, a recognized clinical trajectory points to an early onset, predominantly before 18 years. GD type 3c is primarily caused by homozygosity for <i>GBA</i> pathogenic variant c.1342G&gt;C (p.Asp448His; historically referred to as D409H) and includes visceral, hematological, skeletal, and cardiac abnormalities. Notably, GD type 3c is distinct from other GD types because it is primarily characterized by valvular heart disease. Yet, with less than 50 patients with GD type 3c reported to date, the phenotypic spectrum and extent of cardiac involvement remains ill-defined. We present a 20-year-old female with an atypical presentation of GD type 3c consisting of chronic intermediate uveitis as the presenting feature and the presence of extensive polyneuropathy starting in adolescence which has been previously unreported in GD type 3c. Distinctively, she has maintained normal cardiac function. Moreover, we compare our case with those reported in the literature to broaden awareness of the varied initial presentations of this disease. The diverse presentations seen in GD type 3c, underscored by our case and those previously reported, demonstrate the need for standardized evaluation and management protocols.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"65 5","pages":"313-322"},"PeriodicalIF":0.0,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmd2.12440","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142165637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Huppke–Brendel syndrome: Novel cases and a therapeutic trial with ketogenic diet and N-acetylcysteine","authors":"Katarina Šikić,&nbsp;Tessa M. A. Peters,&nbsp;Udo Engelke,&nbsp;Danijela Petković Ramadža,&nbsp;Tamara Žigman,&nbsp;Ksenija Fumić,&nbsp;Maša Davidović,&nbsp;Sanda Huljev Frković,&nbsp;Tibor Körmendy,&nbsp;Diego Martinelli,&nbsp;Antonio Novelli,&nbsp;Francesca Romana Lepri,&nbsp;Ron A. Wevers,&nbsp;Ivo Barić","doi":"10.1002/jmd2.12439","DOIUrl":"10.1002/jmd2.12439","url":null,"abstract":"<p>Huppke–Brendel syndrome (HBS) is an autosomal recessive disorder caused by <i>SLC33A1</i> mutations, a gene coding for the acetyl-CoA transporter-1 (AT-1). So far it has been described in nine pediatric and one adult patient. Therapeutic trials with copper histidinate failed to achieve any clinical improvement. Here, we describe the clinical characteristics of two novel patients, one of them diagnosed by gene analysis and his sib postmortally based on clinical characteristics. We demonstrate a therapeutic trial with acetylation therapy, consisting of N-acetylcysteine and ketogenic diet, in one of them. We provide biochemical data on N-acetylated amino acids in cerebrospinal fluid (CSF) and plasma before and after starting this treatment regimen. Our results indicate that ketogenic diet and N-acetylcysteine do not seem to normalize the concentrations of N-acetylated amino acids in CSF or plasma. The overall metabolic pattern shows a trend toward lowered levels of N-acetylated amino acids in CSF and to a lesser extent in plasma. Although there are some assumptions, the function of AT-1 is still not clear and further studies are needed to better understand mechanisms underlying this complex disorder.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"65 6","pages":"361-370"},"PeriodicalIF":0.0,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmd2.12439","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141823853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Variable clinical phenotypes of alpha-methylacyl-CoA racemase deficiency: Report of four cases and review of the literature","authors":"Arzu Selamioğlu,&nbsp;Mehmet Cihan Balcı,&nbsp;Meryem Karaca,&nbsp;Youssef Khalil,&nbsp;Rohit Hirachan,&nbsp;Hacer Durmuş Tekçe,&nbsp;Yeşim Gülşen Parman,&nbsp;Asuman Gedikbaşı,&nbsp;Mübeccel Demirkol,&nbsp;Peter Clayton,&nbsp;Gülden Gökçay","doi":"10.1002/jmd2.12437","DOIUrl":"10.1002/jmd2.12437","url":null,"abstract":"<p>Alpha-methylacyl-CoA-racemase (AMACR) deficiency (MIM#604489) is a peroxisomal disorder resulting in the accumulation of pristanic acid, dihydroxycholestanoic acid (DHCA), and trihydroxycholestanoic acid (THCA), with variable clinical features and age of onset from infancy to late adulthood. The purpose of this report is to define clinical variations and follow-up data in AMACR deficiency emphasizing treatment with a review of cases reported in the literature. Here, four patients, from two families, diagnosed with AMACR deficiency and showing phenotypic heterogeneity are presented. A 10-month-old-female presented with coagulopathy, hepatic dysfunction, and elevated pristanic acid, DHCA, and THCA levels. Genetic testing confirmed a homozygous variant c.596G&gt;A in the <i>AMACR</i> gene. Her brother who had macrovesicular hepatosteatosis and elevated pristanic acid levels was diagnosed with family screening. The third patient presented with rhabdomyolysis following a strenuous exercise without any other complaint. Homozygous novel c.1006G&gt;A variant was found on the <i>AMACR</i> gene. His asymptomatic sister carrying the same variant also had elevated pristanic acid levels. They had normal neuropsychologic evaluation. Dietary treatment with low phytanic and pristanic acid content was recommended to the patients but all showed poor compliance. The sibling pairs were followed for periods of 11 and 7 years, respectively. AMACR deficiency is usually described as an adult-onset disorder with neuropsychological problems. The characterization of natural history and new clinical phenotypes may support earlier diagnosis and treatment.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"65 5","pages":"305-312"},"PeriodicalIF":0.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmd2.12437","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141658437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acid sphingomyelinase deficiency and Gaucher disease in adults: Similarities and differences in two macrophage storage disorders","authors":"Eline C. B. Eskes,&nbsp;Laura van Dussen,&nbsp;Johannes M. F. G. Aerts,&nbsp;Martijn J. C. van der Lienden,&nbsp;Mario Maas,&nbsp;Erik M. Akkerman,&nbsp;André B. P. van Kuilenburg,&nbsp;Barbara Sjouke,&nbsp;Carla E. M. Hollak","doi":"10.1002/jmd2.12420","DOIUrl":"10.1002/jmd2.12420","url":null,"abstract":"<p>The lysosomal storage diseases chronic visceral acid sphingomyelinase deficiency (ASMD) and Gaucher disease type 1 (GD1) are both macrophage storage disorders with overlapping clinical manifestations. We compared cross-sectional data on visceral, hematological, and biochemical manifestations of untreated adult patients with chronic visceral ASMD (<i>n</i> = 19) and GD1 (<i>n</i> = 85). Spleen volume, liver volume, and bone marrow fat fraction did not significantly differ between the two disease groups (<i>p</i> &gt;0.05 for all). Chitotriosidase activity was higher in GD1 (GD1: median 30 940 nmol/(mL.h), range 513–201 352, ASMD: median 1693 nmol/(mL.h), range 326–6620, <i>p</i> &lt;0.001), whereas platelet levels were lower (GD1: median 102 10⁹/L, range 16–726, ASMD: median 154 10⁹/L, range 86–484, <i>p</i> &lt;0.010), as were hemoglobin levels (GD1: median 7.8 mmol/L, range 5.0–10.4, ASMD: median 9.0 mmol/L, range 7.0–10.4, <i>p</i> &lt;0.001). No bone complications were reported for ASMD, compared to 33% in GD1 (<i>p</i> &lt;0.005). In ASMD pulmonary disease was more severe as evidenced by a median diffusion capacity of the lungs for carbon monoxide of 73% of predicted (range 26–104), compared to 85% (range 53–126) in GD1 (<i>p</i> = 0.029). In conclusion, bone complications, hematological abnormalities, chitotriosidase activity, and CCL18 levels were more prominent in GD1, while pulmonary manifestations were more common in AMSD. Different secondary pathophysiological processes surrounding sphingomyelin and glucosylceramide accumulation might explain these differences.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"65 5","pages":"330-340"},"PeriodicalIF":0.0,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmd2.12420","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141677930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Riboflavin transporter deficiency in young adults unmasked by dietary changes","authors":"Bregje Jaeger,&nbsp;Mirjam Langeveld,&nbsp;Robert Brunkhorst,&nbsp;Felix Distelmaier,&nbsp;Ana Pop,&nbsp;Nicole I. Wolf,&nbsp;Annet M. Bosch","doi":"10.1002/jmd2.12427","DOIUrl":"https://doi.org/10.1002/jmd2.12427","url":null,"abstract":"<p>Riboflavin transporter deficiency (RTD) is a genetic disorder of reduced riboflavin (vitamin B2) uptake that causes progressive, multifocal neurological dysfunction. Most patients present in early childhood; if patients present later in life, symptoms usually develop more gradually. We report three previously healthy young adults, who developed rapidly progressive neurological symptoms after decreasing dietary intake of meat and dairy. After a diagnostic odyssey, the diagnosis of a riboflavin transporter deficiency was made. Treatment with high dose oral riboflavin (20–40 mg/kg/day) partially reversed symptoms. This case series highlights that reduced riboflavin intake as a result of dietary changes can unmask RTD at a later age. We emphasize the importance of early recognition of this progressive and potentially lethal disease and show that timely treatment with high dose riboflavin is highly effective.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"65 4","pages":"233-238"},"PeriodicalIF":0.0,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmd2.12427","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141537043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Galactokinase 1 is the source of elevated galactose-1-phosphate and cerebrosides are modestly reduced in a mouse model of classic galactosemia","authors":"Linley Mangini,&nbsp;Roger Lawrence,&nbsp;Manuel E. Lopez,&nbsp;Timothy C. Graham,&nbsp;Christopher R. Bauer,&nbsp;Hang Nguyen,&nbsp;Cheng Su,&nbsp;John Ramphal,&nbsp;Brett E. Crawford,&nbsp;Tom A. Hartl","doi":"10.1002/jmd2.12438","DOIUrl":"https://doi.org/10.1002/jmd2.12438","url":null,"abstract":"<p>Classic galactosemia (CG) arises from loss-of-function mutations in the <i>Galt</i> gene, which codes for the enzyme galactose-1-phosphate uridylyltransferase (GALT), a central component in galactose metabolism. The neonatal fatality associated with CG can be prevented by galactose dietary restriction, but for decades it has been known that limiting galactose intake is not a cure and patients often have lasting complications. Even on a low-galactose diet, GALT's substrate galactose-1-phosphate (Gal1P) is elevated and one hypothesis is that elevated Gal1P is a driver of pathology. Here we show that Gal1P levels were elevated above wildtype (WT) in <i>Galt</i> mutant mice, while mice doubly mutant for <i>Galt</i> and the gene encoding galactokinase 1 <i>(Galk1)</i> had normal Gal1P levels. This indicates that GALK1 is necessary for the elevated Gal1P in CG. Another hypothesis to explain the pathology is that an inability to metabolize galactose leads to diminished or disrupted galactosylation of proteins or lipids. Our studies reveal that levels of a subset of cerebrosides—galactosylceramide 24:1, sulfatide 24:1, and glucosylceramide 24:1—were modestly decreased compared to WT. In contrast, gangliosides were unaltered. The observed reduction in these 24:1 cerebrosides may be relevant to the clinical pathology of CG, since the cerebroside galactosylceramide is an important structural component of myelin, the 24:1 species is the most abundant in myelin, and irregularities in white matter, of which myelin is a constituent, have been observed in patients with CG. Therefore, impaired cerebroside production may be a contributing factor to the brain damage that is a common clinical feature of the human disease.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"65 4","pages":"280-294"},"PeriodicalIF":0.0,"publicationDate":"2024-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmd2.12438","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141536876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hereditary tyrosinaemia type 1 in the absence of succinylacetone: 4-oxo 6-hydroxyhepanoate (4OHHA), a putative diagnostic biomarker","authors":"Preeya Rehsi,&nbsp;Karolina Witek,&nbsp;Erin Emmett,&nbsp;Rachel Carling,&nbsp;Charles Turner,&nbsp;Neil Dalton,&nbsp;Tim Hutchin,&nbsp;Nedim Hadzic,&nbsp;Anil Dhawan,&nbsp;Roshni Vara","doi":"10.1002/jmd2.12436","DOIUrl":"https://doi.org/10.1002/jmd2.12436","url":null,"abstract":"<p>Hereditary tyrosinemia type 1 (HT1) is a rare metabolic disease resulting in acute liver failure in early infancy, hypophosphataemic rickets, neurological crises, liver cirrhosis and risk of hepatocellular carcinoma later on in life. It is caused by the deficiency of the enzyme fumarylacetoacetate hydrolase which is involved in the terminal step of the catabolic pathway of tyrosine. Diagnosis is made through clinical suspicion supported by biochemical abnormalities that result from accumulation of upstream metabolites. Detection of succinylacetone (SA) in dried blood spot or urine remains pathognomonic, however it is not always detectable. Here we describe three cases of HT1 presenting with atypical biochemistry, where SA was not always detectable, highlighting the importance of an additional disease biomarker, 4-oxo-6-hydroxyheptanoate.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"65 4","pages":"255-261"},"PeriodicalIF":0.0,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmd2.12436","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141536911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two successful pregnancies -in patients taking Volanesorsen for familial chylomicronemia syndrome","authors":"Subadra Wanninayake,&nbsp;Antonio Ochoa-Ferraro,&nbsp;Karishma Patel,&nbsp;Radha Ramachandran,&nbsp;Anthony S. Wierzbicki,&nbsp;Charlotte Dawson","doi":"10.1002/jmd2.12435","DOIUrl":"https://doi.org/10.1002/jmd2.12435","url":null,"abstract":"<p>Familial chylomicronemia syndrome (FCS) is a rare inherited disorder characterized by severe hypertriglyceridemia, posing a heightened risk of acute pancreatitis. Recently, Volanesorsen, an APOC3 antisense oligonucleotide, gained approval for FCS treatment in the UK. Caution is advised during pregnancy due to limited safety data, although animal studies show no toxicity/teratogenicity. Two case scenarios are presented: In the first case, a patient with FCS continued Volanesorsen injections without having thrombocytopenia during an unplanned pregnancy until third trimester, maintaining triglyceride control. Upon discovering the pregnancy at 38 weeks, Volanesorsen was ceased, and a low-fat diet reinstated. Despite a heightened risk of pancreatitis, no episodes of pancreatitis occurred during the pregnancy. In the second case, stopping Volanesorsen before conception led to elevated triglycerides, and an episode of acute pancreatitis at 22 weeks, despite strict very low-fat diet and fibrate therapy from 14 weeks. At 23 weeks, Volanesorsen was reintroduced concurrently with regular therapeutic plasma exchange. No further episodes of pancreatitis occurred. In both case, fetal health was maintained throughout pregnancy, fetal scans revealed no anomalies, and planned C-sections delivered healthy babies without congenital issues. Both babies are well and developing normally at 24 and 19 months.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"65 4","pages":"249-254"},"PeriodicalIF":0.0,"publicationDate":"2024-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmd2.12435","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141537044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnosis and stabilisation of familial chylomicronemia syndrome in two infants presenting with hypertriglyceridemia-induced acute pancreatitis","authors":"Oliver Heath,&nbsp;Brooke Allender,&nbsp;Joel Smith,&nbsp;Elena Savva,&nbsp;Lucy Spencer,&nbsp;Elizabeth G. Bannister,&nbsp;Natasha J. Brown,&nbsp;Maureen S. Evans,&nbsp;Sharmila Kiss,&nbsp;Thomas H. Rozen,&nbsp;Joy Yaplito-Lee","doi":"10.1002/jmd2.12434","DOIUrl":"10.1002/jmd2.12434","url":null,"abstract":"<p>Familial chylomicronemia syndrome (FCS) is a rare disorder of triglyceride (TG) metabolism caused by loss of function variants in one of five known canonical genes involved in chylomicron lipolysis and clearance—<i>LPL</i>, <i>APOC2</i>, <i>APOA5</i>, <i>LMF1</i>, and <i>GPIHBP1</i>. Pathogenic variants in <i>LPL</i>, which encodes the hydrolytic enzyme lipoprotein lipase, account for over 80%–90% of cases. FCS may present in infancy with hypertriglyceridemia-induced acute pancreatitis and is challenging to manage both acutely and in the long-term. Here, we report our experience managing two unrelated infants consecutively diagnosed with hypertriglyceridemia-induced acute pancreatitis caused by LPL deficiency. Both had elevated TGs at presentation (205 and 30 mmol/L, respectively) and molecular genetic testing confirmed each infant carried a different homozygous pathogenic variant in the LPL gene, specifically, c.987C&gt;A (p.Tyr329Ter) and c.632C&gt;A (p.Thr211Lys). The more severely affected infant had cutaneous xanthomata, lipemia retinalis and lipemic plasma at presentation, and required management in an intensive care setting. Acute stabilisation was achieved using insulin and heparin infusions together with the iterative implementation of a fat-restricted diet, low in long chain triglycerides (LCT) and supplemented with medium chain triglycerides (MCT). In both cases, provision of adequate caloric intake (~110–120 kcal/kg/day) was also found to be important for a sustained TG reduction during the acute phase of management. In summary, a high index of suspicion is required to diagnose FCS in infants with hypertriglyceridemia-induced acute pancreatitis, management of which can be challenging, highlighting the need for more evidence-based recommendations.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"65 4","pages":"239-248"},"PeriodicalIF":0.0,"publicationDate":"2024-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmd2.12434","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141274354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}