Liver histology in children with glycogen storage disorders type VI and IX

Degrassi, Irene; Deheragoda, Maesha; Creegen, David; Mundy, Helen; Mustafa, Ahlam; Vara, Roshni; Hadžić, Nedim

doi:10.1016/j.dld.2020.04.017

Cited by 11 publications

(17 citation statements)

References 27 publications

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“…GSD VI is a rare type of hepatic GSD (Wolfsdorf & Weinstein, 2003), which accounts for only 5.7% (56/980) of all patients with hepatic GSDs in our center. To date, approximately 50 cases have been reported (Aeppli et al, 2020; Beauchamp et al, 2007; Burwinkel et al, 1998; Chang et al, 1998; Degrassi et al, 2020; Liu et al, 2020; Roscher et al, 2014; Szymańska et al, 2020; Tang et al, 2003; Wang et al, 2013). The low incidence may be related to the relatively mild phenotype compared to other types of GSDs, such as Types I and III, thus the parents may be less inclined to bring their children to medical attention.…”

Section: Discussionmentioning

confidence: 99%

“…Once diagnosed, patients are treated with uncooked cornstarch (UCS) and a high protein diet (Kishnani et al, 2019). To date, approximately 50 cases of GSD VI have been reported (Aeppli et al, 2020; Beauchamp et al, 2007; Burwinkel et al, 1998; Chang et al, 1998; Degrassi et al, 2020; Liu et al, 2020; Roscher et al, 2014; Szymańska et al, 2020; Tang et al, 2003; Wang et al, 2013), and several studies have described the long‐term follow‐up of patients with GSD VI (Aeppli et al, 2020; Szymańska et al, 2020). As the clinical presentation of patients with GSD VI is variable and often nonspecific, GSD VI is probably one of the most underdiagnosed types of GSD.…”

Section: Introductionmentioning

confidence: 99%

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Diagnosis and follow‐up of glycogen storage disease (GSD) type VI from the largest GSD center in China

et al. 2022

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Glycogen storage disease (GSD) Type VI is a glycogenolysis disorder caused by variants of PYGL. Knowledge about this disease is limited because only approximately 50 cases have been reported. We investigated the clinical profiles, molecular diagnosis, and treatment outcomes in patients with GSD VI from 2000 to 2021. The main initial clinical features of this cohort include hepatomegaly, short stature, elevated liver transaminases, hypertriglyceridemia, fasting hypoglycemia, and hyperuricemia. After uncooked cornstarch treatment, the stature and biochemical parameters improved significantly (p < 0.05). However, hyperuricemia recurred in most patients during adolescence. Among the 56 GSD VI patients, 54 biallelic variants and two single allelic variants of PYGL were identified, of which 43 were novel. There were two hotspot variants, c.1621‐258_2178‐23del and c.2467C>T p.(Gln823*), mainly in patients from Southwest and South China. c.1621‐258_2178‐23del is a 3.6 kb deletion that results in an out‐of‐frame deletion r.1621_2177del and an in‐frame deletion r.1621_2265del. Our data show for the first time that long‐term monitoring of uric acid is recommended for older GSD VI patients. This study also broadens the variant spectrum of PYGL and indicates that there are two hot‐spot variants in China.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Diagnosis and follow‐up of glycogen storage disease (GSD) type VI from the largest GSD center in China

et al. 2022

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“…To date, 23 variants were identified in PHKB gene in 18 patients with GSD-IXb (Table 1 ). A comparison of the literature showed that manifestation of GSD-IXb was highly variable, ranging from benign mild to moderate, and sometimes aggressive [ 2 , 3 , 6 – 10 ]. The age of GSD-IXb onset can be in young children with a mean age of 3.8 years.…”

Section: Discussionmentioning

confidence: 99%

“…GSD IXb is characterized by hepatomegaly, hypoglycemia, growth retardation, as well as motor developmental delays [ 7 ]. Unlike other hepatic GSDs, symptoms of GSD IXb are often mild, and patients may even become asymptomatic as they grow up [ 8 – 10 ].…”

Section: Introductionmentioning

confidence: 99%

Novel mutations in the PHKB gene in an iranian girl with severe liver involvement and glycogen storage disease type IX: a case report and review of literature

et al. 2021

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Background Glycogen storage disease (GSD) type IXb is one of the rare variants of GSDs. It is a genetically heterogeneous metabolic disorder due to deficient hepatic phosphorylase kinase activity. Diagnosis of GSD can be difficult because of overlapping manifestations. Mutation analysis of the genes related to each type of GSD is supposed to be problem-solving, however, the presence of novel mutations can be confusing. In this case report, we will describe our experience with a young girl with the diagnosis of GSD and two novel mutations related to GSD type IXb. Case presentation A 3-year- old girl presented with short stature, hepatomegaly, and liver cirrhosis. No specific diagnosis was made based on laboratory data, so liver biopsy and targeted-gene sequencing (TGS) were performed to find out the specific molecular basis of her disease. It was confirmed that the patient carries two novel variants in the PHKB gene. The variant in the PHKB gene was classified as pathogenic. Conclusions This is the first reported case of a dual molecular mutation of glycogen storage disease type IXb in the same patient. Two novel variants in PHKB were identified and one of them was a pathogenic split-site mutation. In conclusion, for the first time, identification of the novel variants in this patient expands the molecular and the phenotype basis of dual variants in GSD-IXb.

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“…There are several examples where current non-invasive diagnostic techniques are inadequate for diagnosis (such as in the donor liver, liver allograft and in pediatric liver diseases). [63][64][65] Conversely, there are several examples in the current practice where liver histology may not be necessary and generally offers little diagnostic or therapeutic benefit over other approaches (for example, in NAFLD and alcoholic hepatitis). 66,67 In drug-induced liver injury, liver histology is rarely required but may be indicated when there is no resolution of abnormal liver tests on withdrawal of the putative toxin, when multiple factors may be involved (such as alcohol use) or when there remains uncertainty as to the diagnosis.…”

Section: Current and Future Roles Of Liver Histology Disease Diagnosis Parenchymal Diseasementioning

confidence: 99%

The Need for Alternatives to Liver Biopsies: Non-Invasive Analytics and Diagnostics

Neuberger

Cain

2021

HMER

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Histology remains essential for the diagnosis and management of many disorders affecting the liver. However, the biopsy procedure itself is associated with a low risk of harm to the patient and cost to the health services; samples may not be adequate and are subject to sampling variation. Furthermore, interpretation often depends on the skill of the pathologist. Increasingly, new techniques are becoming available that are altering the indications for liver biopsy. Many diseases of the liver can be diagnosed and managed using serological and radiological techniques; the degree of fibrosis and fat can often be assessed by serological or imaging techniques and the nature of space occupying lesions defined by serology, imaging and use of liquid biopsy. However, these techniques, too, are subject to limitations: sensitivity and specificity is not always adequate for diagnosis or management; some techniques are expensive and often also require expert interpretation. Although there may be less need for liver biopsy today, histology remains the gold standard as well as an essential tool for the diagnosis and management of many conditions, especially where there are multiple pathologies, or where a diagnosis cannot or has not been made by alternative approaches. Until less invasive techniques become more reliable and accessible, liver histology will remain a key investigation.

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Liver histology in children with glycogen storage disorders type VI and IX

Cited by 11 publications

References 27 publications

Diagnosis and follow‐up of glycogen storage disease (GSD) type VI from the largest GSD center in China

Diagnosis and follow‐up of glycogen storage disease (GSD) type VI from the largest GSD center in China

Novel mutations in the PHKB gene in an iranian girl with severe liver involvement and glycogen storage disease type IX: a case report and review of literature

The Need for Alternatives to Liver Biopsies: Non-Invasive Analytics and Diagnostics

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